- Studies of the tandem mukaiyama aldol-lactonization (TMAL) reaction: A concise and highly diastereoselective route to β-lactones applied to the total synthesis of the potent pancreatic lipase inhibitor, (-)-Panclicin D
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A concise and highly diastereoselective route to β-lactones has been developed based on a tandem Mukaiyama aldol-lactonization employing thiopyridylsilylketene acetals and various aldehydes. (-) - Panclicin D, a potent pancreatic lipase inhibitor, was synthesized using this methodology. Recent optimization and extensions of this method are described which include variation of the silyl group and leaving group of the ketene acetal.
- Yang, Hong Woon,Zhao, Cunxiang,Romo, Daniel
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- Preparation and characterization of a series of thiourea derivatives as phase change materials for thermal energy storage
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A series of solid-liquid phase change materials, thiourea derivatives, were prepared via condensation of thiourea with the respective carboxyl chlorides (lauroyl chloride, myristoyl chloride, and palmitoyl chloride) and were then characterized by using FT-IR, 1H-NMR, differential scanning calorimetry (DSC), and thermogravimetric (TG) analysis. The thiourea derivatives (1,3-didodecanoyl thiourea, 1,3-ditetradecanoyl thiourea, and 1,3-dihexadecanoyl thiourea) were structurally symmetric and had long alkyl groups to crystallize. Thermal analysis by DSC and spectroscopic investigation by FT-IR spectroscopy were performed on the samples before and after thermal cycling tests to determine thermal reliability. The maximum latent heats of melting and freezing of the thiourea derivatives were found to be 114.6 and -110.0 J/g for 1,3-didodecanoyl thiourea, 119.5 and -122.4 J/g for 1,3-ditetradecanoyl thiourea, and 148.8 and -142.7 J/g for 1,3-dihexadecanoyl thiourea after accelerated thermal cycling. A TG instrument was used to determine the starting point of degradation in the thiourea derivatives; it was found that the thiourea derivatives degraded at sufficiently higher temperatures than the expected utility temperatures.
- Alkan, Cemil,Tek, Yusuf,Kahraman, Derya
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- DECOMPOSITION DE L'ACIDE PEROXYDODECANOIQUE DANS CCl4: ROLE DU SOLVANT
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The decomposition of peroxydodecanoic acid in refluxing CCl4 proceeds by a complex process involving ionic and radical reactions.In the latter, this study has confirmed the important role, shown previously, of the character (nucleophilic or electrophilic) of the radical on the regioselectivity of the attack on the peracid. The (*)CCl3 radicals (electrophilic) proceed by abstraction of the H of the peracid; the analysis of the products confirms the presence of intermediary R-(*)CO radicals resulting from the equilibrium: This explains why the decomposition of a peracid in CCl4 leads mainly to the formation of the corresponding acid whereas in a hydrocarbon solvent one observes essentially the decarboxylation leading to the alcohol according to the mechanism previously proved.
- Sorba, J.,Fossey, J.,Lefort, D.,Nedelec, J. Y.
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- Lipophilic pyrylium salts in the synthesis of efficient pyridinium-based cationic lipids, gemini surfactants, and lipophilic oligomers for gene delivery
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Several new classes of pyridinium cationic lipids were synthesized and tested as gene delivery agents. They were obtained through a procedure that generates simultaneously the heterocyclic ring and the positively charged nitrogen atom, using lipophilic pyrylium salts as key intermediates that react with primary amines, yielding pyridinium salts. The choice of the appropriately substituted primary amine, diamine or polyamine, allows the design of the shape of the final lipids, gemini surfactants, or lipophilic polycations. We report also a comprehensive structure-activity relationship study that identified the most efficient structural variables at the levels of the hydrophobic anchor, linker, and counterion for these classes of pyridinium cationic lipids. This study was also aimed at finding the best liposomal formulation for the new transfection agents.
- Ilies, Marc Antoniu,Seitz, William A.,Johnson, Betty H.,Ezell, Edward L.,Miller, Aaron L.,Thompson, E. Brad,Balaban, Alexandru T.
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- Synthesis of neoglycolipids based on D-lactose
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A synthesis was performed of amphiphilic D-lactose derivatives differing by the length and number of aliphatic chains. The compounds may be applied to the carbohydrate modification of phosphatidylcholine liposomes.
- Gur'eva,Budanova,Sebyakin
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- Trifluoromethyl ketone inhibitors of fatty acid amide hydrolase: A probe of structural and conformational features contributing to inhibition
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The examination of a series of trifluoromethyl ketone inhibitors of Fatty Acid Amide Hydrolase (FAAH, oleamide hydrolase, anandamide amidohydrolase) is detailed in efforts that define structural and conformational properties that contribute to enzyme inhibition and substrate binding. The results imply an extended bound conformation, highlight a role for the presence, position, and stereochemistry of a Δ cis double bond, and suggest little apparent role for C11-C18/C22 of the fatty acid amide substrates.
- Boger, Dale L.,Sato, Haruhiko,Lerner, Aaron E.,Austin, Bryce J.,Patterson, Jean E.,Patricelli, Matthew P.,Cravatt, Benjamin F.
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- Synthesis and preliminary biochemical assessment of ethyl-terminated perfluoroalkylamine oxide surfactants
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The synthesis and usefulness in membrane biochemistry of a new class of surfactants have been investigated. 1-Ethyl-2-dimethylamine oxide polar heads were grafted onto a hydrocarbon, a fluorocarbon or an ethyl-capped fluorocarbon hydrophobic tail. The ability of the resulting surfactants to extract and/or to stabilize in aqueous solution a test membrane protein, cytochrome b6 f, was evaluated. While it is not a detergent, the hemifluorinated derivative efficiently kept purified cytochrome b6 f soluble, native and functional. The data suggest that alkyl-capped fluorocarbon surfactants provide an interesting alternative to classical detergents for handling membrane proteins in aqueous solutions under non-dissociating conditions.
- Chaudier, Yann,Zito, Francesca,Barthélémy, Philippe,Stroebel, David,Améduri, Bruno,Popot, Jean-Luc,Pucci, Bernard
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- Liquid crystalline and light emitting polyacetylenes: Synthesis and properties of biphenyl-containing poly(1-alkynes) with different functional bridges and spacer lengths
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Biphenyl-(Biph-) containing 1-alkynes (3 and 4) and their polymers (1 and 2) with varying bridge groups and spacer lengths were synthesized and the effects of the structural variation on their properties, especially their mesomorphism and photoluminescence behaviors, were studied. The acetylene monomers 3(3) [HC≡C(CH2)3O-Biph-OCO(CH2)10CH 3] and 4(m) [HC≡C(CH2)m OCO-Biph-OCO(CH2)10-CH3, m = 3,4] were prepared by sequential etherization and esterification reactions of 1-alkynes. While 3(3) exhibits enantiotropic crystal E and SmB mesophases, its structural cousin 4(3) displays only monotropic SmB phase. Enantiotropic SmA and SmB mesophases are, however, developed when the spacer length is increased to 4. Polymerizations of the monomers are affected by Mo-, W-, Rh-, and Fe-based catalysts, with the WCl6-Ph4Sn catalyst giving the best results (isolation yield up to 85% and Mw up to 59000). The polymers were characterized by IR, UV, NMR, TGA, DSC, POM, XRD, and PL analyses. Compared to 1(3), 2(3) shows a red-shifted absorption, a higher Ti, and a better packed interdigitated bilayer SmAd structure, while the mesophase of 2(4) involves mionolayer-packing arrangements of the mesogens. Upon photoexcitation, 1(3) emits almost no light but 2(m) gives a strong ultraviolet emission (λmax ~ 350 nm), whose intensity increases with the spacer length.
- Lam, Jacky W.Y.,Dong, Yuping,Cheuk, Kevin K.L.,Luo, Jingdong,Xie, Zhiliang,Kwok, Hoi Sing,Mo, Zhishen,Tang, Ben Zhong
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- Acene Ring Size Optimization in Fused Lactam Polymers Enabling High n-Type Organic Thermoelectric Performance
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Three n-type fused lactam semiconducting polymers were synthesized for thermoelectric and transistor applications via a cheap, highly atom-efficient, and nontoxic transition-metal free aldol polycondensation. Energy level analysis of the three polymers demonstrated that reducing the central acene core size from two anthracenes (A-A), to mixed naphthalene-anthracene (A-N), and two naphthalene cores (N-N) resulted in progressively larger electron affinities, thereby suggesting an increasingly more favorable and efficient solution doping process when employing 4-(2,3-dihydro-1,3-dimethyl-1H-benzimidazol-2-yl)-N,N-dimethylbenzenamine (N-DMBI) as the dopant. Meanwhile, organic field effect transistor (OFET) mobility data showed the N-N and A-N polymers to feature the highest charge carrier mobilities, further highlighting the benefits of aryl core contraction to the electronic performance of the materials. Ultimately, the combination of these two factors resulted in N-N, A-N, and A-A to display power factors (PFs) of 3.2 μW m-1 K-2, 1.6 μW m-1 K-2, and 0.3 μW m-1 K-2, respectively, when doped with N-DMBI, whereby the PFs recorded for N-N and A-N are among the highest reported in the literature for n-type polymers. Importantly, the results reported in this study highlight that modulating the size of the central acene ring is a highly effective molecular design strategy to optimize the thermoelectric performance of conjugated polymers, thus also providing new insights into the molecular design guidelines for the next generation of high-performance n-type materials for thermoelectric applications.
- Chen, Hu,Moser, Maximilian,Wang, Suhao,Jellett, Cameron,Thorley, Karl,Harrison, George T.,Jiao, Xuechen,Xiao, Mingfei,Purushothaman, Balaji,Alsufyani, Maryam,Bristow, Helen,De Wolf, Stefaan,Gasparini, Nicola,Wadsworth, Andrew,McNeill, Christopher R.,Sirringhaus, Henning,Fabiano, Simone,McCulloch, Iain
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- A new method for the synthesis of 5-fluorouracil prodrugs
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Bromo-tris(dimethylamino)-phosphonium-hexafluorophosphate (BROP) is a particularly suitable reagent for synthesising some 5-fluorouracil prodrugs in a one step reaction. Several acids, especially retinoic acid, were bound to the N1 of 5-fluorou
- Jolima?tre, Pascale,André-Barres, Christiane,Malet-Martino, Myriam,Martino, Robert,Rico-Lattes, Isabelle
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- Self-Assembly and Characterization of Supramolecular [60]Fullerene-Containing 2,6-Diacylamidopyridine with Uracil Derivative by Hydrogen-Bonding Interaction
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matrix presented Novel, self-assembly systems of uracil, derivatives with organofullerene by a three-point hydrogen-bonding interaction were designed and established. The formation of hydrogen bonding was established by 1H NMR studies in CDCl3.
- Shi, Zhiqiang,Li, Yuliang,Gong, Haofei,Liu, Minghua,Xiao, Shengxiong,Liu, Huibiao,Li, Hongmei,Xiao, Shengqiang,Zhu, Daoben
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- A novel α-aminophosphonic acid-modified acrylamide-based hydrophobic associating copolymer with superb water solubility for enhanced oil recovery
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As a non-renewable resource, the rational exploitation of oil has attracted a large amount of attention. Among many methods for enhanced oil recovery, polymer flooding is the most suitable method of chemical flooding for non-marine reservoirs and therefore various modified acrylamide-based copolymers have been studied. In this study, a novel α-aminophosphonic acid-modified hydrophobic associating copolymer was successfully synthesized by copolymerization of acrylamide, acrylic acid, N-allyldodecanamide and 1-(dimethylamino)allylphosphonic acid. The copolymer was characterized by FT-IR, 1H NMR and thermogravimetry and exhibited superior water solubility and thickening capability. Subsequently, the shear resistance, temperature resistance and salt tolerance of the copolymer solution were investigated. The value of apparent viscosity retention of a 2000 mg L-1 copolymer solution was as high as 58.55 mPa s at a shear rate of 170 s-1 and remained at 40.20 mPa s at 120 °C. The values of apparent viscosity retention of 55.41 mPa s, 59.95 mPa s and 52.97 mPa s were observed in solutions of 10000 mg L-1 NaCl, 1200 mg L-1 MgCl2, and 1200 mg L-1 CaCl2, respectively. These were better than those of partially hydrolyzed polyacrylamide under the same conditions. In addition, an increase of up to 14.52% in the oil recovery rate compared with that for water flooding could be achieved in a core flooding test using a 2000 mg L-1 copolymer solution at 65 °C.
- Gou, Shaohua,Zhang, Qin,Yang, Cheng,Li, Qing,Xu, Shuhui,Wu, Yuanpeng,Guo, Qipeng
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- Dual photo- and pH-responsive supramolecular nanocarriers based on water-soluble pillar[6]arene and different azobenzene derivatives for intracellular anticancer drug delivery
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Two novel types of supramolecular nanocarriers fabricated by the amphiphilic host-guest inclusion complex formed from water-soluble pillar[6]arene (WP6) and azobenzene derivatives G1 or G2 have been developed, in which G1 is structurally similar to G2 but has an extra phenoxy group in its hydrophobic region. Supramolecular micelles can be initially formed by WP6 with G1, which gradually transform into layered structures with liquid-crystalline properties, whereas stable supramolecular vesicles are obtained from WP6 and G2, which exhibit dual photo- and pH-responsiveness. Notably, the resulting WP6a??G2 vesicles can efficiently encapsulate anticancer drug mitoxantrone (MTZ) to achieve MTZ-loaded vesicles, which maintain good stability in a simulated normal physiological environment, whereas in an acid environment similar to that of tumor cells or with external UV irradiation, the encapsulated drug is promptly released. More importantly, cytotoxicity assay indicates that such vesicles have good biocompatibility and the MTZ-loaded vesicles exhibit comparable anticancer activity to free MTZ, especially with additional UV stimulus, whereas its cytotoxicity for normal cells was remarkably reduced. Flow cytometric analysis further confirms that the cancer cell death caused by MTZ-loaded vesicles is associated with apoptosis. Therefore, the dual pH- and UV-responsive supramolecular vesicles are a potential platform for controlled release and targeted anticancer drug delivery.
- Hu, Xiao-Yu,Jia, Keke,Cao, Yu,Li, Yan,Qin, Shan,Zhou, Fan,Lin, Chen,Zhang, Dongmei,Wang, Leyong
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- Bioresponsive deciduous-charge amphiphiles for liposomal delivery of DNA and siRNA
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Purpose: Biolabile cationic lipids were developed for efficient intracellular delivery of DNA and siRNA. Methods: The compounds have been designed starting from the membrane lipid DOPC in a way they may loose their cationic charge when exposed to an acidic and/or enzymatic stimulus, such as those met during the journey of a lipoplex in biological media. Results: They demonstrated remarkable efficiency to deliver DNA in various cell lines (BHK-21, Calu-3, NCI-H292, and A549), with no significant cytotoxicity. Furthermore, two of the compounds (carbonate-based DOPC derivatives) revealed able to deliver small interfering RNA in U87Luc and A549Luc cancer cells and to mediate a selective 70-80% knockdown of the stably transfected luciferase gene. Conclusions: The results show that the described bioresponsive cationic lipids have high DNA and siARN delivery activity which is encouraging in view of delivering a therapeutic nucleic acid to pulmonary tissues in vivo.
- Pierrat, Philippe,Kereselidze, Dimitri,Wehrung, Patrick,Zuber, Guy,Pons, Francoise,Lebeau, Luc
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- Cationic amphiphiles with fatty acyl chain asymmetry of coconut oil deliver genes selectively to mouse lung
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Recent structure-activity studies have revealed a dramatic influence of hydrophobic chain asymmetry in enhancing gene delivery efficacies of synthetic cationic amphiphiles (Nantz, M. H. et al. Mol. Pharmaceutics2010, 7, 786-794; Koynova, R. et al. Mol. Pharmaceutics2009, 6, 951-958). The present findings demonstrate for the first time that such a transfection enhancing influence of asymmetric hydrocarbon chains observed in pure synthetic cationic amphiphiles also works for cationic amphiphiles designed with natural, asymmetric fatty acyl chains of a food-grade oil. Herein, we demonstrate that cationic amphiphiles designed with the natural fatty acyl chain asymmetry of food-grade coconut oil are less cytotoxic and deliver genes selectively to mouse lung. Despite lauroyl chains being the major fatty acyl chains of coconut oil, both the in vitro and In vivo gene transfer efficiencies of such cationic amphiphiles were found to be remarkably superior (>4-fold) to those of their pure dilauroyl analogue. Mechanistic studies involving the technique of fluorescence resonance energy transfer (FRET) revealed higher biomembrane fusibility of the cationic liposomes of the coconut amphiphiles than that of the symmetric dilauroyl analogue. AFM study revealed pronounced fusogenic nonlamellar structures of the liposomes of coconut amphiphiles. Findings in the FRET and cellular uptake study, taken together, support the notion that the higher cellular uptake resulting from the more fusogenic nature of the liposomes of coconut amphiphiles 1 are likely to play a dominant role in making the coconut amphiphiles transfection competent.
- Chandrashekhar, Voshavar,Srujan, Marepally,Prabhakar, Rairala,Reddy, Rakesh C.,Sreedhar, Bojja,Rentam, Kiran K. R.,Kanjilal, Sanjit,Chaudhuri, Arabinda
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- The influence of varied amide bond positions on hydraphile ion channel activity
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Hydraphile compounds have been prepared in which certain amine nitrogens have been replaced by amide residues. The amide bonds are present either in the side chain, the spacer chain, or the central relay. Sodium cation transport through phospholipid vesicles mediated by each hydraphile was assessed. All of the amide-containing hydraphiles showed increased levels of Na+ transport compared to the parent compound, but the most dramatic rate increase was observed for sidearm amine to amide replacement. We attribute this enhancement to stabilization of the sidearm in the bilayer to achieve a better conformation for ion conduction. Biological studies of the amide hydraphiles with Escherichia coli and Bacillus subtilis showed significant toxicity only with the latter. Further, the consistency between the efficacies of ion transport and toxicity previously observed for non-amidic hydraphiles was not in evidence. the Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2006.
- Weber, Michelle E.,Wang, Wei,Steinhardt, Sarah E.,Gokel, Michael R.,Leevy, W. Matthew,Gokel, George W.
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- Prodrug compound and application thereof in treatment of cancer
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The present invention provides a compound indicated by a formula (I), pharmaceutically acceptable salts or esters thereof, a pharmaceutical composition of the compound, and the use of the compound andthe pharmaceutical composition in inhibition or regulation of tyrosine kinase activity, and treatment of tyrosine kinase mediated disease symptoms or disorders including cancer.
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Paragraph 0109-0110
(2021/03/06)
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- Catalyst for synthesizing acyl chloride compounds and application thereof
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The invention relates to a catalyst for synthesizing an acyl chloride compound and application of the catalyst. The structural formula is as shown in the specification, and in the formula, R is alkali of which the carbon atom number is 1-12. The catalyst is capable of effectively increasing the product yield, improving the production efficiency and lowering the production cost of acyl chloride, and has wide application prospects. The invention further provides a method for synthesizing acyl chloride with the catalyst.
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Paragraph 0043-0047
(2020/10/20)
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- ABUSE-RESISTANT LONG-ACTING RELEASE OPIOID PRODRUGS
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There are provided, prodrugs of opioid such as levorphanol or morphine, having enhanced physical and chemical stability to resist tampering and to make long- acting release formulations, and pharmaceutically accepted salts and solvates thereof. There are also provided methods of using the disclosed compounds as abuse deterrent products.
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Paragraph 93; 95
(2020/07/31)
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- A dibenzocyclooctyne derivative and application thereof
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The invention relates to a dibenzocyclooctyne derivative and application thereof. The dibenzocyclooctyne derivative is especially used for carrying out click reaction with azide compounds to prepare stable 1,2,3-triazole compounds, and the latter have a wide range of uses in labeling glycans, proteins and lipids of living cells, glycoprotein enrichment of proteomics, protein and oligonucleotide modification, and tissue reconstruction engineering.
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Paragraph 0026; 0032; 0034
(2019/07/10)
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- COMPOUNDS, COMPOSITONS AND METHODS RELATED TO ANTIMICROBIAL APPLICATIONS
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The present disclosure is in the field of polymers and pharmaceuticals/antimicrobials. The disclosure provides compounds based on SNAP (synthetic novel antimicrobial polymer) technology, compositions and methods of managing microbial infections including surgical site infections (SSIs). The present compounds are used as a management/therapeutic strategy to target microbial infections and have advantages including excellent antimicrobial potency, biofilm disruption ability, broad spectrum activity against various organisms covering both gram negative and gram positive bacteria as well as fungal pathogens, and low toxicity profile to ensure a healthy therapeutic window for use in humans.
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Page/Page column 82-83
(2018/03/25)
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- Method for preparing acyl chloride by catalyzing phosgene and acid
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The invention discloses a method for preparing acyl chloride by catalyzing phosgene and acid. The method includes the following steps that 1, with carboxylic acid as a raw material, a catalyst and a solvent are added, and under the condition that the temperature is maintained to range from 20 DEG C to 200 DEG C, phosgene is introduced into a reaction flask for a reaction; 2, after the molar ratio of carboxylic acid to phosgene reaches 1:1.0-1:10, phosgene introduction is stopped, reacted mixed liquor is obtained and filtered, obtained filter liquor is subjected to reduced pressure distillation at a high vacuum degree to obtain acyl chloride, and an obtained filter cake continues to serve as the catalyst in the step 1 to be recycled. Compared with an existing catalyst adopted for preparing acyl chloride according to a phosgene method, the catalyst used in the method is small in dosage, convenient to recycle, easy to separate from a product, better in product quality, safe, stable and environmentally friendly, generated solid waste is greatly reduced, the experience of operators is greatly improved, and safety risks are lowered.
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Paragraph 0052; 0053; 0054
(2016/10/20)
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- Preparation method of acyl chloride
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The invention relates to a preparation method of acyl chloride. The method comprises the following steps that 1, carboxylic acid is added into a reactor, or carboxylic acid is dissolved in organic solvent, a device is connected, and the temperature is raised to 100 DGE C-250 DEG C; 2, phosgene is introduced into the reactor for a reaction, and then the temperature is decreased to room temperature; 3, nitrogen is introduced, residual phosgene and hydrogen chloride are cleaned away, reaction liquid which is reacted without solvent is subjected to decompression distillation and purification directly, and needed acyl chloride is obtained; reaction liquid which is reacted with the solvent is subjected to decompression distillation to remove the solvent, and needed acyl chloride is obtained. According to the preparation method of acyl chloride, no catalyst is added, the risks that in the synthesizing process, due to the fact that the catalyst is dissolved, color of the finial product of acyl chloride is increased, and the catalyst is remained in late products are avoided, after the reaction is finished, high-quality acyl chloride can be obtained through decompression distillation, and the technological process is simple; due to the fact that in the whole technological process, except for absorbable and available phosgene, hydrogen chloride and carbon dioxide, no other three waste is discharged, the preparation method of acyl chloride is environmentally friendly, and the good implement value is achieved.
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Paragraph 0040; 0041
(2016/11/28)
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- A laurel acyl amino acid synthetic method of sodium
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The invention relates to a synthetic method of lauric acyl amino acid sodium, particularly to a synthetic method which uses lauric acid and phosgene as raw materials. The synthetic method comprises the following steps: ensuring that the reaction lasts for 1 to 20 hours at a temperature of 60 to 100 DEG C with the effect of organic amide catalyst; obtaining acyl chloride through vacuum distillation after the reaction is finished; dripping lauric acyl chloride obtained according to the phosgene method into amino acids alkaline solution for reaction; controlling and ensuring the pH value to be within the range of 8 to 10, the reaction temperature to be 15 to 20 DEG C, and the reaction time to be 4 to 5 hours; carrying out cooling after the reaction is finished; acidizing the reaction solution to pH 1 to 2 with hydrochloric acid solution; filtering, washing and drying white sediment to obtain lauric acyl amino acid; dissolving the prepared lauric acyl amino acid with alcohol; adding alcohol solution with sodium hydroxide of equal molar amount; and crystallizing, sucking, filtering and drying after cooling to obtain the lauric acyl amino acid sodium. According to the invention, the synthetic method is reasonable in process, high in reaction efficiency and good in product quality; the three wastes are seldom generated; and no residual phosphorus and sulfur are contained in the product. Therefore, the synthetic method can be widely used in the production of high-end surface active agents, and has significant utility value and social and economic benefits.
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Paragraph 0021; 0022
(2016/10/09)
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- Synthesis of novel ethyl 1-ethyl-6-fluoro-7-(fatty amido)-1,4-dihydro-4-oxoquinoline-3-carboxylate derivatives and their biological evaluation
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A series of novel ethyl 1-ethyl-6-fluoro-7-(fatty amido)-1,4-dihydro-4-oxoquinoline-3-carboxylate derivatives were prepared through multistep synthesis. The key step in the synthesis was to obtain the C-7 fatty amide derivative. The azide was selectively formed at C-7 position using sodium azide at 60 °C. Subsequently, the azide was reduced under mild conditions using zinc and ammonium chloride to form the corresponding amine. The synthesized derivatives were further subjected to biological evaluation studies like cytotoxicity against a panel of cancer cell lines such as DU145, A549, SKOV3, MCF7 and normal lung cells, IMR-90 as well as with antimicrobial and antioxidant activities. It was observed that the carboxylated quinolone derivatives with hexanoic (8a), octanoic (8b), lauric (8d) and myristic (8e) moieties exhibited promising cytotoxicity against all the tested cancer cell lines. The results also suggested that hexanoic acid-based fatty amide carboxylated quinolone derivative (8a) exhibited promising activity against both bacterial and fungal strains and significant antibacterial activity was observed against Staphylococcus aureus MTCC 96 (MIC value of 3.9 μg/mL). The compound 8a also showed excellent anti-biofilm activity against Staphylococcus aureus MTCC 96 and Bacillus subtilis MTCC 121 with MIC values of 2.1 and 4.6 μg/mL, respectively.
- Venepally, Vijayendar,Prasad,Poornachandra,Kumar, C. Ganesh,Jala, Ram Chandra Reddy
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supporting information
p. 613 - 617
(2016/01/09)
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- Synthesis and Surface-Active Properties of a Homologous Series of Star-Like Triple-Chain Anionic Surfactants Derived from 1,1,1-Tris(hydroxymethyl)ethane
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A novel homologous series of trimeric anionic surfactants, 3C n TE3CNa (where n is a fatty acid chain length of 7, 10, or 12), with three hydrocarbon chains and three carboxylate heads connected via tri-etheric bonds were synthesized from long-chain α-bromo fatty acids and a triol, 1,1,1-tris(hydroxymethyl)ethane. The obtained trimeric carboxylic acids were esterified and purified by silica gel column chromatography, then hydrolyzed with dilute sodium hydroxide solution to form a series of trimeric carboxylate surfactant products. All prepared compounds were analyzed by IR, 1H NMR, and 13C NMR spectroscopy to confirm their chemical structures. Their surface-active properties were investigated. The critical micelle concentrations (cmc) of 3C n TE3CNa were in the range of 0.12-0.71 mmol/L, and the surface tensions at the cmc (γ cmc) were 29.3-34.8 mN/m.
- Li, Xu,Xing, Fenglan,Xu, Qun,Sun, Xiaolong,Wang, Yuping,Wang, Liyan,Wang, Pinglang
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p. 129 - 135
(2016/01/09)
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- Structure, supramolecular organization and phase behavior of N-acyl-β-alanines: Structural homologues of mammalian brain constituents N-acylglycine and N-acyl-GABA
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N-Acyl-β-alanines (NABAs) are structural homologues of N-acylglycines (NAGs) and N-acyl-γ-aminobutyric acids (NAGABAs), and achiral isomers of N-acylalanines, which are all present in mammalian brain and other tissues and modulate activity of biological receptors with various functions. In the present study, we synthesized and characterized a homologous series of NABAs bearing saturated acyl chains (n = 8-20) and investigated their supramolecular organization and thermotropic phase behavior. In differential scanning calorimetric (DSC) studies, most of the NABAs gave one or two minor transitions before the main chain-melting phase transition in the dry state as well as upon hydration with water, but gave only a single transition when hydrated with buffer (pH 7.6). Transition enthalpies (ΔHt) and entropies (ΔSt), obtained from the DSC studies showed linear dependence on the chain length in the dry state and upon hydration with buffer, whereas odd-even alteration was observed when hydrated with water. The crystal structures of N-lauroyl-β-alanine (NLBA) and N-myristoyl-β-alanine (NMBA) were solved in monoclinic system in the P21/c space group. Both NLBA and NMBA were packed in tilted bilayers with head-to-head (and tail-to-tail) arrangement with tilt angles of 33.28° and 34.42°, respectively. Strong hydrogen bonding interactions between [sbnd]COOH groups of the molecules from opposite leaflets as well as N[sbnd]H?O hydrogen bonds between the amide groups from adjacent molecules in the same leaflet as well as dispersion interactions between the acyl chains stabilize the bilayer structure. The d-spacings calculated from powder X-ray diffraction studies showed odd-even alteration with odd-chain length compounds exhibiting higher values as compared to the even-chain length ones and the tilt angles calculated from the PXRD data are higher for the even chain NABAs. These observations are relevant to developing structure-activity relationships for these amphiphiles and understand how NABAs differ from their homologues and isomers, namely NAGs, NAGABAs, and N-acylalanines.
- Sivaramakrishna,Swamy, Musti J.
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- Α-terpineol fatty acid ester derivatives and use
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The invention belongs to the technical field of medicine and discloses alpha-terpineol aliphatic ester and a preparation with the compound. The alpha-terpineol aliphatic ester is formed by alpha-terpineol and fatty acid after esterification reaction. According to a method, first, fatty acid and thionyl chloride react to prepare acyl chloride, and then acyl chloride and alpha-terpineol react to prepare the alpha-terpineol aliphatic ester. The alpha-terpineol ester can be used as penetration enhancers to be used for external preparations of patching agents, Cataplasm, ointment agents, gel agents and the like, accordingly, the percutaneous absorptive amount of medicine is improved, and the alpha-terpineol aliphatic ester is good percutaneous absorptive penetration enhancers and has wide application prospect.
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Paragraph 0053; 0054
(2017/03/18)
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- Method to Produce N-Acyl Amino Acid Surfactants Using N-Acyl Amino Acid Surfactants or the Corresponding Anhydrides as Catalysts
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A process of producing N-acyl amino acid based surfactants of Formula I, wherein, R is selected from C6 to C22 alkyl group, R1 is selected from H, C1 to C4 alkyl, R2 is selected from all groups on α carbon of natural amino acids, R3 is selected from COOX, CH2—SO3X, X is selected from Li+, Na+ or K+. The process comprising steps of: A) preparing fatty acid chlorides by halogenating fatty acids with either phosgene or thionyl chloride in the presence of catalytic amount of same or other N-acyl amino acid surfactant of Formula I or anhydrides of same surfactant; andB) reacting fatty acid chloride of step (A) with an amino acid in the presence of a base.
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Paragraph 0055
(2015/05/26)
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- Investigation of fatty acid conjugates of 3,5-bisarylmethylene-4-piperidone derivatives as antitumor agents and human topoisomerase-IIα inhibitors
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A series of five 3,5-bisarylidene-4-piperidones designed as analogs of curcumin and their twenty five fatty acid conjugates were synthesized as candidate anticancer agents. The fatty acid conjugates were designed for efficient delivery of these compounds at the targeted cancer sites. The cytostatic potential of these compounds was evaluated against three representative cancer cell lines namely murine leukemic L1210 cells, and human T-lymphocyte CEM cells and cervical HeLa cells. Most compounds were found to exhibit significant anti-cancer activity in vitro. QSAR studies indicated electrophilicity of these compounds towards cellular nucleophiles may have a key role to play in their cytostatic activity. Representative compounds were also tested for topoisomerase IIα inhibitory potential, which indicated strong catalytic inhibition of the enzyme in vitro. The data showed that the fatty acid conjugates also possessed robust antioxidant activity in multiple analyses. This study also indicated that these compounds prompted significantly lower cellular damage in human fibroblasts than a currently used cancer drug sorafenib in vitro. The wide spectrum of anticancer action, supplemented with antioxidant potential along with non-toxic manifestations, certainly augment the anticancer candidacy of the novel fatty acid conjugates.
- Potter, Elizabeth,Jha, Mamta,Bhullar, Khushwant S.,Rupasinghe, H.P. Vasantha,Balzarini, Jan,Jha, Amitabh
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p. 411 - 421
(2015/01/30)
-
- Controllable Fabrication of Various Supramolecular Nanostructures Based on Nonamphiphilic Azobenzene Derivatives and Pillar[6]arene
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Various novel types of supramolecular nanostructures formed by nonamphiphilic azobenzene derivatives, G1 or G2 have been successfully fabricated, where G2 is structurally similar with G1 but an extra phenoxy group is connected with the azobenzene motif. M
- Qin, Shan,Xiong, Shuhan,Han, Yang,Hu, Xiao-Yu,Wang, Leyong
-
supporting information
p. 107 - 111
(2015/03/30)
-
- Preparation and properties of a novel form-stable phase change material based on a gelator
-
A series of gelators (Gm, m is the length of the alkyl tails, m = 2, 4, 6, 8, 10, 12, 14, 16 and 18) containing 4,4′-diaminodiphenylmethane moieties were synthesized. The chemical structures of Gm were confirmed by 1H NMR and MS. The form-stable phase change materials (FSPCMs) were prepared by introducing Gm into paraffin. The minimum gelation concentration (MGC) and gel-to-sol transition temperature (TGS) properties were tested by the "tube-testing method". It found that Gm (m = 2, 4, 6) was insoluble in paraffin, while the MGC and TGS of Gm (m = 8, 10, 12, 14, 16, 18) increased with the increase of alkyl chain. The structure and morphology of the PCMs were systematically investigated by FT-IR, POM, 1D WXAD and SEM. Experimental results revealed that paraffin was restricted because the gelators could self-assemble into three-dimensional netted structures, leading to form the shape-stable PCMs without leakage even above their melting point. The thermal properties were studied by DSC. The research showed that the G18/paraffin FSPCMs exhibited excellent thermal stability and high heat storage density. The shape stability of G18/paraffin was investigated by rheological measurements, indicating that solid hard gel soft gel liquid was observed with the increase of temperature. This work is useful in the comprehensive academic research and industrial application of PCMs.
- Wu, Dang,Wen, Wen,Chen, Sheng,Zhang, Hailiang
-
supporting information
p. 2589 - 2600
(2015/02/19)
-
- Reversal of P-gp and BCRP-mediated MDR by tariquidar derivatives
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Abstract With an aim to generate non-toxic, specific and highly potent multidrug resistance (MDR) modulators, a novel series of anthranilic acid amide-substituted tariquidar derivatives were synthesized. The new compounds were evaluated for their cytotoxicity toward normal human colon fibroblasts (CCD18-Co), human gastric epithelial cell line (HFE) and primary rat liver cells, and for their ability to inhibit P-gp/BCRP-mediated drug efflux and reversal of P-gp and BCRP-mediated MDR in parental and drug-resistant cancer cell lines (LCC6 MDR1, MCF-7 FLV1000, R-HepG2, SW620-Ad300). While tariquidar is highly toxic to normal cells, the new derivatives exhibited much lower or negligible cytotoxicity. Some of the new tariquidar derivatives inhibited both P-gp and BCRP-mediated drug efflux whereas a few of them bearing a sulfonamide functional group (1, 5, and 16) are specific to P-gp. The new compounds were also found to potentiate the anticancer activity of the transporter substrate anticancer drugs in the corresponding transporter-overexpressing cell lines. The extent of resistance reversal was found to be consistent with the transporter inhibitory effect of the new derivatives. To further understand the mechanism of P-gp and BCRP inhibition, the tariquidar derivatives were found to interact with the transporters using an antibody-based UIC2 or 5D3 shift assay. Moreover, the transporters-inhibiting derivatives were found to modulate the ATPase activities of the two MDR transporters. Our data thus advocate further development of the new compounds for the circumvention of MDR.
- Li, Xu-Qin,Wang, Lin,Lei, Yan,Hu, Tao,Zhang, Fei-Long,Cho, Chi-Hin,To, Kenneth K.W.
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p. 560 - 572
(2015/07/28)
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- Differential scanning calorimetric and powder X-ray diffraction studies on a homologous series of N-acyl-L-alanine esters with matched chains (n = 9-18)
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A homologous series of two chain derivatives of L-alanine, namely N-acyl L-alanine alkyl esters (NAAEs), bearing matched, saturated, acyl and alkyl chains (n= 9-18) have been synthesized. The thermotropic phase transitions and supramolecular structure of NAAEs were investigated by differential scanning calorimetry (DSC) and powder X-ray diffraction (PXRD). Results obtained from DSC studies indicate that the transition temperatures (T t), enthalpies (ΔH t) and entropies (ΔS t) exhibit odd-even alternation with compounds bearing odd acyl and alkyl chains showing higher values of T t, ΔH t and ΔS t as compared to NAAEs with even acyl and alkyl chains. However, the transition enthalpies and entropies of the odd- and even chain length series independently exhibit a linear dependence on the chain length. The d-spacings obtained from PXRD increase linearly with chain length with an increment of 1.76 ?/CH 2, suggesting that NAAEs adopt either a tilted bilayer structure or a bent structure. The present results provide a thermodynamic and structural basis for investigating the interaction of NAAEs with other membrane lipids, which in turn can shed light in understanding how they can enhance the transdermal permeability of stratum corneum.
- Sivaramakrishna,Swamy, Musti J.
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p. 1627 - 1635
(2015/12/01)
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- Agent having neurotrophic factor-like activity
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The present invention provides a pharmaceutical agent having high safety and a neurotrophic factor-like activity, which contains, as an active ingredient, any one compound included in fatty acids each having 8 carbon atoms (C8) or having 10 carbon atoms (C10) to 12 carbon atoms (C12) or fatty acid esters thereof, such as 3,7-dimethyloctanoic acid ethyl ester, geranicacidethyl ester, and the like, eachof whichhas 8 carbonatoms (C8), decanoic acid methyl ester, trans-2-decenoic acid, trans-2-decenoic acid methyl ester, trans-2-decenoic acid ethyl ester, trans-2-decenoic acid-2-decenyl ester, trans-2-decenoic acid cyclohexyl ester, trans-2-decenoic acid isopropyl ester, trans-3-decenoic acid methyl ester, trans-9-decenoic acid methyl ester, and the like, each of which has 10 carbon atoms (C10), trans-10-undecenoic acid methyl ester, trans-10-undecenoic acid ethyl ester, and the like, each of which has 11 carbon atoms (C11), and dodecanoic acid, and the like, each of which has 12 carbon atoms (C12), or salts thereof or prodrugs thereof.
- -
-
Paragraph 0037-0038
(2016/01/25)
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- NOVEL LIPIDS AND LIPID NANOPARTICLE FORMULATIONS FOR DELIVERY OF NUCLEIC ACIDS
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Compounds are provided having the following structure: (I) or a pharmaceutically acceptable salt, tautomer or stereoisomer thereof, wherein R1a, R1b, R2a, R2b, R3a, R3b, R4a, R4b, R5, R6, R7, R8, R9, L1, L2, a, b, c, d and e are as defined herein. Use of the compounds as a component of lipid nanoparticle formulations for delivery of a therapeutic agent, compositions comprising the compounds and methods for their use and preparation are also provided.
- -
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Page/Page column 76
(2016/05/02)
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- MANUFACTURING METHOD OF ALIPHATIC ACID CHLORIDE AND ALIPHATIC ACID CHLORIDE
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PROBLEM TO BE SOLVED: To provide a manufacturing method of aliphatic acid chloride having no cloudiness and stable color tone with time by a simple manufacturing method. SOLUTION: A reaction product is obtained by reacting aliphatic acid having 8 to 22 carbon atoms and phosphorus trichloride of 1/3 to 2/3 mol equivalent to the aliphatic acid to produce aliphatic acid chloride and removing byproduct phosphorus acid after standing layer separation. By purifying the reaction production, a purified product having the phosphorus content of the byproduct phosphorus acid of 0.20 wt.% or less is obtained. Phosphorus trichloride of 0.03 to 0.07 wt.% in terms of the phosphorus content is added to the purified product. COPYRIGHT: (C)2016,JPOandINPIT
- -
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Paragraph 0047
(2016/10/17)
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- MANUFACTURING METHOD OF ALIPHATIC ACID CHLORIDE AND ALIPHATIC ACID CHLORIDE
-
PROBLEM TO BE SOLVED: To provide aliphatic acid chloride having no cloudiness and stable color tone with time by a simple manufacturing method. SOLUTION: A reactive product is obtained by reacting aliphatic acid having 8 to 22 carbon atoms and phosphorus trichloride of 1/3 to 2/3 equivalent to the aliphatic acid to produce aliphatic acid chloride and removing phosphorus acid as a byproduct. Then the reactive product is treated at a temperature of 10 to 60°C, nitrogen flow rate of 1.0×10-4 to 1.0×10-2 m3/kg hr and pressure of 133.3×10-2 to 133.3×102 Pa and reacting unreacted phosphorus acid with the aliphatic acid and the aliphatic acid chloride to produce an organic phosphorous compound as well as the unreacted phosphorus trichloride is removed to obtain aliphatic acid chloride. COPYRIGHT: (C)2016,JPOandINPIT
- -
-
Paragraph 0039-0040
(2016/12/12)
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- Binding interaction of an anionic amino acid surfactant with bovine serum albumin: physicochemical and spectroscopic investigations combined with molecular docking study
-
The interaction of a synthesised amino acid surfactant, sodium-N-dodecanoylphenylalaninate (AAS) with a transport protein, bovine serum albumin (BSA) has been uncovered employing various physicochemical and spectroscopic techniques like tensiometry, electro kinetic potential measurements, steady-state fluorometry, time-resolved measurements and circular dichroism (CD) at physiological pH and 298 K. The difference in tensiometric responses of AAS in the absence and presence of BSA indicates a significant interaction operative between them. The zeta (ξ) potential measurements have been taken into account in assigning the type of binding interaction between them. The steady-state fluorescence study reveals the sequential unfolding of BSA with stepwise addition of AAS. Stern-Volmer and modified Stern-Volmer plots, Scatchard plots and thermodynamic parameters have been employed to find the type of binding of AAS to BSA. Life-time measurements have been carried out to shed light on the relative amplitude of binding of AAS to the two Trp residues of BSA namely Trp-134 and Trp-213. The changes in protein secondary structure induced by AAS are unveiled by CD measurements. Quantum mechanical calculations involving density functional theory (DFT) and molecular docking analysis have been undertaken to highlight the interactive phenomenon between the two. Thus this work shows a total inspection of an amino acid surfactant-BSA interaction.
- Dasmandal, Somnath,Kundu, Arjama,Rudra, Suparna,Mahapatra, Ambikesh
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p. 79107 - 79118
(2015/10/05)
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- METHOD TO PRODUCE N-ACYL AMINO ACID SURFACTANTS USING N-ACYL AMINO ACID SURFACTANTS OR THE CORRESPONDING ANHYDRIDES AS CATALYSTS
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A process of producing N-acyl amino acid based surfactants of Formula (I), wherein, R is selected from C6 to C22 alkyl group, R1 is selected from H, C1 to C4 alkyl, R2 is selected from all groups on a carbon of natural amino acids, R3 is selected from COOX, CH2-SO3X, X is selected from Li+, Na+ or K+; said process comprising steps of A) preparing fatty acid chlorides by halogenating fatty acids with either phosgene or thionyl chloride in the presence of catalytic amount of same or other N-acyl amino acid surfactant of Formula (I) or anhydrides of same surfactant, Formula (II), wherein, R = C6 to C22 alkyl group, R1 = H, C1 to C4 alkyl, R2 = all groups on α carbon of natural amino acids, n = 0 to 4, X = C, SO and B) reacting fatty acid chloride of step (A) with an amino acid in the presence of a base under typical aqueous Schotten Baumann conditions such that said process does not employ a step of purification.
- -
-
Page/Page column 24-25
(2014/03/25)
-
- CONJUGATE-BASED ANTIFUNGAL AND ANTIBACTERIAL PRODRUGS
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The invention provides conjugate-based antifungal or antibacterial prodrugs formed by coupling at least one anti-fungal agent or antibacterial agent with at least one linker and/or carrier. The prodrugs are of formula: (i) (AFA)m-X-(L)n; (ii) [(AFA)m′-X]p-L; (iii) AFA-[X-(L)n′]q; or (iv) (AFA)m″-X, wherein: AFA is an antifungal agent or an antibacterial agent; L is a carrier; X is a linker; m ranges from 1 to 10; n ranges from 2 to 10; m′ is 1 to 10; p is 1 to 10; n′ is 1 to 10; and q is 1 to 10, provided that q′ and n are not both 1; and m″ is 1 to 10. The invention also provides nanoparticles comprising the conjugate-based prodrugs. Additionally, the invention also provides non-conjugated antifungal and antibacterial agents in the form of nanoparticles.
- -
-
Paragraph 0430
(2015/01/06)
-
- A simple and efficient synthesis of substituted 2,2′-bithiophene and 2,2′:5′,2″-terthiophene
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A simple and efficient approach is developed for the synthesis of substituted 2,2′-bithiophene- and 2,2′:5′,2″- terthiophene-5-carboxylic acids and esters which is based on thiophene ring closure in the Fiesselmann reaction. Using this method, derivatives containing a long alkyl chain with or without an end functional group or an aryl substituent can be conveniently prepared.
- Kostyuchenko, Anastasia S.,Averkov, Alexey M.,Fisyuk, Alexander S.
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supporting information
p. 1833 - 1835
(2014/05/06)
-
- Synthesis, characterization and biological evaluation of novel diesters of 4,4'-dihydroxy azoxy benzene with long chain carboxylic acids
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Synthesis of novel symmetrical azoxy diesters have been prepared by the reaction of 4,4'-dihydroxyazoxy benzene with aliphatic acid halides of varying chain lengths. The synthesized compounds have been characterized by spectral and analytical data. These symmetrical azoxy diesters exhibit good antifungal activity against six fungal strains (Mucor species, Aspergillus niger, Aspergillus flavus, Alternaria solani, Fusarium solani and Aspergillus fumigatus) and antitumor activities while no significant antibacterial activity has been observed. These synthesized compounds are also potent free radical scavengers.
- Shehzadi, Sumaira,Siddiqi, Humaira Masood,Qasim, Malik Muhammed,Fawad, Musfirah,Manan, Abdul,Khan, Naeema,Saleem, Samreen,Bashir, Farah,Mirza, Bushra
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p. 462 - 472
(2014/08/05)
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- Fabrication of organogels achieved by prodrug-based organogelators of ketoprofen
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The treatment strategy of curing diseases using prodrugs of an anti-inflammatory drug is widespread. In the present study, we report on the synthesis of prodrugs of ketoprofen, consisting of a derivatization of ketoprofen and long hydrocarbon chain of fat
- Mahire, Rahul R.,Agrawal, Deepika S.,Patil, Devanand K.,More, Dhananjay H.
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p. 33286 - 33291
(2014/08/18)
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- Structure and thermotropic phase behavior of a homologous series of n -Acylglycines: Neuroactive and antinociceptive constituents of biomembranes
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N-Acylglycines (NAGs) with different acyl chains have been found in the mammalian brain and other tissues. They exhibit significant biological and pharmacological properties and appear to play important roles in communication and signaling pathways within and between cells. In view of this, a homologous series of NAGs have been synthesized and characterized in the present study. Differential scanning calorimetric (DSC) studies show that the transition enthalpies and entropies of dry as well as hydrated NAGs exhibit a linear dependence on the acyl chain length. Most of the NAGs show a minor transition below the chain-melting phase transition, suggesting the presence of polymorphism in the solid state. Structures of N-myristoylglycine (NMG) and N-palmitoylglycine (NPG) were solved in monoclinic system with C2/c and P21 space groups, respectively. Analysis of the crystal structures show that NAGs are organized in a bilayer fashion, with head-to-head (and tail-to-tail) arrangement of molecules. The acyl chains in both structures are essentially perpendicular to the bilayer plane, which is consistent with a lack of odd-even alternation in the thermodynamic properties. The bilayer is stabilized by strong hydrogen bonding interactions between COOH groups of the molecules from opposite leaflets as well as N-H···O hydrogen bonds between the amide groups of adjacent molecules in the same leaflet and dispersion interactions among the acyl chains. Powder X-ray diffraction data show that the d-spacings for the NAGs with different acyl chains (n = 8-20) exhibit a linear dependence on the chain length, suggesting that all the NAGs investigated here adopt a similar packing arrangement in the crystal lattice. These observations are relevant for understanding the role of N-acylglycines in biological membranes.
- Reddy, S. Thirupathi,Krovi, Krishna Prasad,Swamy, Musti J.
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p. 4944 - 4954
(2014/12/10)
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- Inhibition of human α-methylacyl CoA racemase (AMACR): A target for prostate cancer
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The enzyme α-methylacyl CoA racemase (AMACR) is involved in the metabolism of branched-chain fatty acids and has been identified as a promising therapeutic target for prostate cancer. By using the recently available human AMACR from HEK293 kidney cell cultures, we tested a series of new rationally designed inhibitors to determine the structural requirements in the acyl component. An N-methylthiocarbamate (Ki=98nM), designed to mimic the proposed enzyme-bound enolate, was found to be the most potent AMACR inhibitor reported to date. Enolate mimicry: A range of inhibitors were designed and synthesized to determine the structural requirements for inhibition of the prostate cancer target racemase AMACR using the recently available human enzyme from HEK293 kidney cell cultures. An N-methylthiocarbamate (Ki=98nM), designed to mimic the proposed enzyme-bound enolate, is the most potent AMACR inhibitor reported to date.
- Carnell, Andrew J.,Kirk, Ralph,Smith, Matthew,Mckenna, Shane,Lian, Lu-Yun,Gibson, Robert
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supporting information
p. 1643 - 1647
(2013/10/21)
-
- Discovery of a series of thiazole derivatives as novel inhibitors of metastatic cancer cell migration and invasion
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Effective inhibitors of cancer cell migration and invasion can potentially lead to clinical applications as a therapy to block tumor metastasis, the primary cause of death in cancer patients. To this end, we have designed and synthesized a series of thiazole derivatives that showed potent efficacy against cell migration and invasion in metastatic cancer cells. The most effective compound, 5k, was found to have an IC50 value of 176 nM in the dose-dependent transwell migration assays in MDA-MB-231cells. At a dose of 10 μM, 5k also blocked about 80% of migration in HeLa and A549 cells and 60% of invasion of MDA-MB-231 cells. Importantly, the majority of the derivatives exhibited no apparent cytotoxicity in the clonogenic assays. The low to negligible inhibition of cell proliferation is a desirable property of these antimigration derivatives because they hold promise of low toxicity to healthy cells as potential therapeutic agents. Mechanistic studies analyzing the actin cytoskeleton by microscopy demonstrate that compound 5k substantially reduced cellular f-actin and prevented localization of fascin to actin-rich membrane protrusions. These results suggest that the antimigration activity may result from impaired actin structures in protrusions that are necessary to drive migration.
- Zheng, Shilong,Zhong, Qiu,Jiang, Quan,Mottamal, Madhusoodanan,Zhang, Qiang,Zhu, Naijue,Burow, Matthew E.,Worthylake, Rebecca A.,Wang, Guangdi
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supporting information
p. 191 - 196
(2013/03/28)
-
- From a remarkable manifestation of polar effects in a radical fragmentation to the convergent synthesis of highly functionalized ketones
-
A new radical addition/C-C bond fragmentation process is reported. Vinyl carbinols derived from 2-methyl-2-phenylpropanal react with radicals generated from xanthates to give the corresponding ketones. The radical cleavage reaction proceeds under mild conditions, in good to high yield, and in the presence of the unprotected carbinol. Highly functionalized 1,5-diketones and pyridines are readily available using this approach.
- Debien, Laurent,Zard, Samir Z.
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supporting information
p. 3808 - 3811
(2013/04/23)
-
- Prodrugs of N-dicarboximide derivatives of the rat selective toxicant norbormide
-
Norbormide [5-(α-hydroxy-α-2-pyridylbenzyl)-7-(α-2- pyridylbenzylidene)-5-norbornene-2,3-dicarboximide] (NRB), an existing but infrequently used rodenticide, is known to be uniquely toxic to rats but relatively harmless to other rodents and mammals. However, one major drawback of NRB as a viable rodenticide relates to an evolutionary aversion developed by the rat leading to sub-lethal dosing due to either its unpleasant 'taste' or rapid onset of effects. A series of NRB-derived prodrugs were prepared in an effort to 'mask' this acute response. Their synthesis and biological evaluation (in vitro vasoconstrictory activity, in vitro hydrolytic and enzymatic stability and lethality/palatability in vivo) is described. Prodrug 2 displayed the most promising profile with respect to a delay in the onset of symptoms and was subsequently demonstrated to be significantly more palatable to rats. Moreover, prodrug 25 was found to be largely accepted by rats in a choice trial, resulting in high mortality.
- Rennison, David,Laita, Olivia,Conole, Daniel,Jay-Smith, Morgan,Knauf, Jan,Bova, Sergio,Cavalli, Maurizio,Hopkins, Brian,Linthicum, Darwin S.,Brimble, Margaret A.
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supporting information
p. 5886 - 5899
(2013/09/12)
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- The relationship between the structure and properties of amino acid surfactants based on glycine and serine
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Two series of surfactants based on glycine and serine were synthesized with aproic acid, octanoic acid, decanoic acid, dodecanoic acid, tetradecanoic acid and hexadecanoic acid. All the surfactants were characterized by MS and 1H NMR, the structures of the synthesized surfactants are correct and the signals in MS and 1H NMR can be explained. The reaction conditions, surface properties and foam properties were studied. For the two series of surfactants, critical micelle concentration (CMC) and γ CMC (surface tension at CMC) decrease and surface activity is enhanced as the length of carbon chain increases. The surfactants with tetradecanoyl and hexadecanoyl groups show a good foaming property and especially, the long-chain acyl-serine performs better. These are all related to the hydromethyl group in the serine.
- Qiao, Weihong,Qiao, Yangyang
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p. 821 - 828
(2013/11/06)
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- Synthesis and biological evaluation of novel ferrocene-naphthoquinones as antiplasmodial agents
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This work deals with the synthesis and evaluation of new compounds designed by combination of 1,4-naphthoquinone and ferrocene fragments in a 3-ferrocenylmethyl-2-hydroxy-1,4-naphthoquinone arrangement. A practical coupling reaction between 2-hydroxy-1,4-naphthoquinone and ferrocenemethanol derivatives has been developed. This procedure can be carried out "on-water", at moderate temperatures and without auxiliaries or catalysts, with moderate to high yields. The synthesized derivatives have shown significant in vitro antiplasmodial activity against chloroquine-sensitive and resistant Plasmodium falciparum strains and it has been shown that this activity is not related to the inhibition of biomineralization of ferriprotoporphyrin IX. Binding energy calculations and docking of these compounds to cytochrome b in comparison with atovaquone have been performed.
- García-Barrantes, Pedro M.,Lamoureux, Guy V.,Pérez, Alice L.,García-Sánchez, Rory N.,Martínez, Antonio R.,San Feliciano, Arturo
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p. 548 - 557
(2013/12/04)
-
- Electrospray ionization and collision induced dissociation mass spectrometry of primary fatty acid amides
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Primary fatty acid amides are a group of bioactive lipids that have been linked with a variety of biological processes such as sleep regulation and modulation of monoaminergic systems. As novel forms of these molecules continue to be discovered, more emphasis will be placed on selective, trace detection. Currently, there is no published experimental determination of collision induced dissociation of PFAMs. A select group of PFAM standards, 12 to 22 length carbon chains, were directly infused into an electrospray ionization source Quadrupole Time of Flight Mass Spectrometer. All standards were monitored in positive mode using the [M + H]+ peak. Mass Hunter Qualitative Analysis software was used to calculate empirical formulas of the product ions. All PFAMs showed losses of 14 m/z indicative of an acyl chain, while the monounsaturated group displayed neutral losses corresponding to H2O and NH3. The resulting spectra were used to propose fragmentation mechanisms. Isotopically labeled PFAMs were used to validate the proposed mechanisms. Patterns of saturated versus unsaturated standards were distinctive, allowing for simple differentiation. This determination will allow for fast, qualitative identification of PFAMs. Additionally, it will provide a method development tool for selection of unique product ions when analyzed in multiple reaction monitoring mode.
- Divito, Erin B.,Davic, Andrew P.,Johnson, Mitchell E.,Cascio, Michael
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experimental part
p. 2388 - 2394
(2012/07/27)
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- Analogs of 2-arachidonoylglycerin containing the no-donor group
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1, 3-Dinitroglyceryl esters of fatty acids, analogs of endocannabinoid 2-arachidonoylglycerin, were synthesized. Various methods for esterifying fatty acids with glycerine dinitrate were developed.
- Serkov,Gretskaya,Bezuglov
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p. 367 - 370
(2012/10/30)
-
- Inhibition of PCAF histone acetyltransferase and cytotoxic effect of N-acylanthranilic acids
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Small molecule HAT inhibitors are useful tools to unravel the role of histone acetyltransferases (HATs) in the cell and have relevance for oncology. We synthesized a series of N-acylanthranilic acids (11-16) and of N-acyl-5-hydroxyanthranilic acids (17-22) bearing C6, C8, C10, C12, C14, along with C16 acyl chain at the 2-amino position of anthranilic acid or 5-hydroxyanthranilic acid. Enzyme inhibition of these compounds was investigated, using in vitro PCAF HAT assays. All synthesized compounds (65-76%) showed similar inhibitory activity to anacardic acid (68%) at 100 μM. The cytotoxicity, against one normal cell line (HSF) and eight cancer cell lines (HT-29, HCT-116, MDA-231, A-549, Hep3B, Caski, HeLa and Caki), were evaluated by the SRB method.
- Park, Woong Jae,Ma, Eunsook
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p. 1379 - 1386
(2013/01/15)
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- Inhibition of PCAF histone acetyltransferase, cytotoxicity and cell permeability of 2-acylamino-1-(3-or 4-carboxy-phenyl)benzamides
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Small molecule HAT inhibitors are useful tools to unravel the role of histone acetyltransferases (HATs) in the cell and they also have relevance in oncology. We synthesized a series of 2-acylamino-1-(3- or 4-carboxyphenyl) benzamides 8-19 bearing C6, C8, C10, C12, C14, and C16 acyl chains at the 2-amino position of 2-aminobenzoic acid. Enzyme inhibition of these compounds was investigated using in vitro PCAF HAT assays. The inhibitory activities of compounds 8-10, 16, and 19 were similar to that of anacardic acid, and 17 was found to be more active than anacardic acid at 100 μM. Compounds 11-15 showed the low inhibitory activity on PCAF HAT. The cytotoxicity of the synthesized compounds was evaluated by SRB (sulforhodamine B) assay against seven human cancer cell lines: HT-29 (colon), HCT-116 (colon), MDA-231 (breast), A549 (lung), Hep3B (hepatoma), HeLa (cervical) and Caki (kidney) and one normal cell line (HSF). Compound 17 was more active than anacardic acid against human colon cancer (HCT 116, IC50: 29.17 μM), human lung cancer (A549, IC 50: 32.09 μM) cell lines. 18 was more active than anacardic acid against human colon cancer (HT-29, IC50: 35.49 μM and HCT 116, IC50: 27.56 μM), human lung cancer (A549, IC50: 30.69 μM), and human cervical cancer (HeLa, IC50: 34.41 μM) cell lines. The apparent permeability coefficient (Papp, cm/s) values of two compounds (16 and 17) were evaluated as 68.21 and 71.48 × 10 -6 cm/s by Caco-2 cell permeability assay.
- Park, Woong Jae,Ma, Eunsook
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p. 13116 - 13131
(2013/02/22)
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- Synthesis and surface active properties of a novel linear dodecyl diphenyl ether sulfonate Gemini surfactant
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The linear dodecyl diphenyl ether sulfonate gemini surfactant (C 12-DLADS) has been synthesized by a new route from lauric acid according to a five-step reaction sequence consisting of acidification, Friedel-Crafts acylation, Clemmensen reduction, sulfonation and a neutralization reaction. The surfactant and intermediates were characterized by 1H-NMR, HPLC/MS and elemental analysis. The properties have been studied by surface tension (γCMC) and conductivity measurements. The thermodynamic parameters of micellization were calculated. The test results show that C12-DLADS has lower critical micelle concentration (CMC) and better capability for lowering the γCMC. The γCMC and CMC are 36.04 mN/m and 6.03 × 10-4 mol/L respectively at 45 °C. Moreover, with the increase in temperature, the conductivity of C12-DLADS increased, while the counterion binding K0 decreased. The thermodynamic data show that the micellization process for the surfactant C12-DLADS is entropy driven. AOCS 2012.
- Hujun, Xu,Qicheng, Liu,Dandan, Chen,Xiaoya, Liu
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p. 703 - 707
(2013/02/25)
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- Synthesis and critical micelle concentration of a series of gemini alkylphenol polyoxyethylene nonionic surfactants
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A series of gemini n-alkylphenol polyoxyethylene surfactants (GAP) were successfully synthesized and their molecular structure were confirmed by NMR and FTIR spectrum. Using the same synthesis route, a Gemini nonylphenol polyoxyethylene surfactant (GNP) was synthesized using an industrial nonylphenol product and paraformaldehyde, and its molecular structure was also characterized by 1H-NMR and FTIR spectra. The optimal reaction conditions were established. The critical micelle concentration (CMC) values of GAP were determined by means of Wilhelmy plate method and steady-state fluorescence probe method. The experimental results show how the lengths of the hydrophilic polyoxyethylene chain and the hydrophobic tail alter the CMC values. The CMC values of the GAP are found to be much lower than those of corresponding conventional single tail nonionic surfactants of the polyethoxylated alkylphenol type, which indicates that the gemini species exhibit a better surface activity. AOCS 2011.
- Yang, Fang,Li, Gang,Xu, Nian,Liu, Rong,Zhang, Song-Mei,Wu, Zeng-Jiang
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experimental part
p. 339 - 345
(2012/06/30)
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- Dodecanoic acid derivatives: Synthesis, antimicrobial evaluation and development of one-target and multi-target QSAR models
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In this study a series of dodecanoic acid derivatives (1-30) were synthesized and evaluated for in vitro antimicrobial activity against the panel of Gram positive, Gram negative bacterial and fungal strains. 4-Nitro phenyl dodecanoate (4) and quinolin-8-yl dodecanoate (5) emerged as most effective antibacterial agents, and 1-(4-benzylpiperazin- 1-yl) dodecan-1-one (15) was found to be the most effective antifungal agent amongst the synthesized dodecanoic acid derivatives. Quantitative structure activity relationship (QSAR) studies performed by the development of one-target and multi-target models indicated that multitarget model was effective in describing the antimicrobial activity of dodecanoic acid derivatives as well demonstrated the importance of topological parameter, zero-order molecular connectivity index (0X). Springer Science+Business Media, LLC 2010.
- Sarova, Devinder,Kapoor, Archana,Narang, Rakesh,Judge, Vikramjeet,Narasimhan, Balasubramanian
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body text
p. 769 - 781
(2012/05/20)
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- Alkyl sulfonyl derivatized PAMAM-G2 dendrimers as nonviral gene delivery vectors with improved transfection efficiencies
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Amphiphilic dendrimer-based gene delivery vectors bearing peripheral alkyl sulfonyl hydrophobic tails were constructed using low-generation PAMAM-G2 as the core and functionalized by means of the aza-Michael type addition of its primary amino groups to vinylsulfone derivatives as an efficient tool for surface engineering. While the unmodified PAMAM-G2 was unable to efficiently transfect eukaryotic cells, functionalized PAMAM-G2 dendrimers were able to bind DNA at low N/P ratios, protect DNA from digestion with DNase I and showed high transfection efficiencies and low cytotoxicity. Dendrimers with a C18 alkyl chain produced transfection efficiencies up to 3.1 fold higher than LipofectAMINE 2000 in CHO-k1 cells. The dendriplexes based in functionalized PAMAM-G2 also showed the ability to retain their transfection properties in the presence of serum and the ability to transfect different eukaryotic cell lines such as Neuro-2A and RAW 264.7. Taking advantage of the vinylsulfone chemistry, fluorescent PAMAM-G2 derivatives of these vectors were prepared as molecular probes to determine cellular uptake and internalization through a clathrin-independent mechanism.
- Morales-Sanfrutos, Julia,Megia-Fernandez, Alicia,Hernandez-Mateo, Fernando,Giron-Gonzalez, Ma Dolores,Salto-Gonzalez, Rafael,Santoyo-Gonzalez, Francisco
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experimental part
p. 851 - 864
(2011/03/22)
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- Synthesis, modelling and kinetic assays of potent inhibitors of purple acid phosphatase
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Purple acid phosphatases (PAPs) are binuclear metallohydrolases that have been isolated from various mammals, plants, fungi and bacteria. In mammals PAP activity is associated with bone resorption and can lead to bone metabolic disorders such as osteoporosis; thus human PAP is an attractive target to develop anti-osteoporotic drugs. Based on a previous lead compound and rational drug design, acyl derivatives of α-aminonaphthylmethylphosphonic acid were synthesised and tested as PAP inhibitors. Kinetic analysis showed that they are good PAP inhibitors whose potencies improve with increasing acyl chain length. Maximum potency is reached when the number of carbons in the acyl chain is between 12 and 14. The most potent inhibitor of red kidney bean PAP is the dodecyl-derivative with Kic = 5 μM, while the most potent pig PAP inhibitor is the tetradecyl-derivative with Kic = 8 μM, the most potent inhibitor of a mammalian PAP yet reported.
- Mohd-Pahmi, Siti Hajar,Hussein, Waleed M.,Schenk, Gerhard,McGeary, Ross P.
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supporting information; experimental part
p. 3092 - 3094
(2011/06/24)
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- Synthesis and biological evaluation of novel aliphatic amido-quaternary ammonium salts for anticancer chemotherapy: Part i
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We synthesized novel aliphatic amido-quaternary ammonium salts in an effort to discover anticancer agents that increase Ras homolog gene family, member B, (RhoB) levels. These compounds exert anti-proliferative activities against several human cancer cell types. Seventeen compounds, varying in aliphatic carbon chain length and N-substituents, were synthesized and their biological activities were evaluated. Of these 17 compounds, compound 3i emerged as the most promising anticancer compound by promoting apoptosis through the RhoB mediated pathway. Potent biological activities observed for these novel aliphatic amido-quaternary ammonium salt analogues support their potential as anticancer, chemotherapeutic agents.
- Yang, Jee Sun,Song, Doona,Lee, Boah,Ko, Won Jin,Park, Song-Kyu,Won, Misun,Lee, Kiho,Kim, Hwan Mook,Han, Gyoonhee
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experimental part
p. 2861 - 2866
(2011/06/27)
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