- Chili pepper fruits: Presumed precursors of fatty acids characteristic for capsaicinoids
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Capsaicin is a molecule unique to fruits from the genus Capsicum. It is responsible for the pungent sensation and displays valuable pharmacological properties. Despite the fruits' economic importance and decades of research, the regulation of the content of capsaicinoids in individual fruits is not completely elucidated, and no agricultural cultivation of chili of defined pungency is assured. Precursor candidates of the fatty acid moiety of the capsaicinoids, especially for the unique 8-methyl-trans-6-nonenoic acid, were examined. Thioesters, acyl-ACP and acyl-CoA, were isolated from the placenta of Capsicum fruits by means of DEAE-Sepharose chromatography, selectively converted to the corresponding N-butylamides, and analyzed by GC-MS. Fatty acid moieties characteristic for capsaicinoids were identified. In two different varieties (Capsicum chinense var. Habanero orange and Capsicum annuum var. Jalapeno) it was shown that the fatty acid pattern corresponds to the distribution pattern of the capsaicinoids formed up to this time. The acyl-thioester fractions contained already the 8-methyl-trans-6-nonenoic acid.
- Thiele, Roland,Mueller-Seitz, Erika,Petz, Michael
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- Synthesis, Physicochemical Properties, and Thermo-Oxidative Stability of Diesters of 5,7-Dimethyl-1,3-Adamantanediol and 5,7-Dimethyl-1,3-bis(Hydroxymethyl)adamantane
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A series of diesters on the basis of 5,7-dimethyl-1,3-adamantanediol and 5,7-dimethyl-1,3- bis(hydroxymethyl)adamantane and C3–C10 aliphatic acids have been synthesized and their physicochemical and thermo-oxidative properties have been studied. The properties of the esters obtained have been compared to those of trimethylolpropane and neopentyl glycol esters.
- Ivleva,Baimuratov,Demidov,Lukashenko,Malinovskaya, Yu. A.,Klimochkin, Yu. N.,Tyshchenko,Kulikova,Pozdnyakov,Ovchinnikov,Rudyak
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- Reaction of long-chain vanillyl esters with ch-acids and 2-naphthylamine
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The previously unknown4-(alkyl-11-oxo-7,8,9,10,11,12-hexahydrobenzo[a] acridin-12-yl)-and4-(alkyl-1,8-dioxo-2,3,4,5,6,7,8,9-octahydro-1H-xanthen-9-yl) -2-methoxyphenyl esters of aliphatic (C5-C7, C 12) carboxylic acids were synthesizedvia cascade heterocyclization of cyclohexane-1,3-dione and dimedone with 2-naphthylamine and long-chain vanillyl esters.
- Kozlov,Basalaeva,Dikusar
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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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- Conformation, and Charge Tunneling through Molecules in SAMs
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This paper demonstrates that the molecular conformation (in addition to the composition and structure) of molecules making up self-assembled monolayers (SAMs) influences the rates of charge tunneling (CT) through them, in molecular junctions of the form AuTS/S(CH2)2CONR1R2//Ga2O3/EGaIn, where R1 and R2 are alkyl chains of different length. The lengths of chains R1 and R2 were selected to influence the conformations and conformational homogeneity of the molecules in the monolayer. The conformations of the molecules influence the thickness of the monolayer (i.e. tunneling barrier width) and their rectification ratios at ±1.0 V. When R1 = H, the molecules are well ordered and exist predominantly in trans-extended conformations. When R1 is an alkyl group (e.g., R1 H), however, their conformations can no longer be all-trans-extended, and the molecules adopt more gauche dihedral angles. This change in the type of conformation decreases the conformational order and influences the rates of tunneling. When R1 = R2, the rates of CT decrease (up to 6.3×), relative to rates of CT observed through SAMs having the same total chain lengths, or thicknesses, when R1 = H. When R1 H R2, there is a weaker correlation (relative to that when R1 = H or R1 = R2) between current density and chain length or monolayer thickness, and in some cases the rates of CT through SAMs made from molecules with different R2 groups are different, even when the thicknesses of the SAMs (as determined by XPS) are the same. These results indicate that the thickness of a monolayer composed of insulating, amide-containing alkanethiols does not solely determine the rate of CT, and rates of charge tunneling are influenced by the conformation of the molecules making up the junction.
- Belding, Lee,Root, Samuel E.,Li, Yuan,Park, Junwoo,Baghbanzadeh, Mostafa,Rojas, Edwin,Pieters, Priscilla F.,Yoon, Hyo Jae,Whitesides, George M.
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- Potent anticonvulsant urea derivatives of constitutional isomers of valproic acid
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Valproic acid (VPA) is a major antiepileptic drug (AED); however, its use is limited by two life-threatening side effects: teratogenicity and hepatotoxicity. Several constitutional isomers of VPA and their amide and urea derivatives were synthesized and evaluated in three different anticonvulsant animal models and a mouse model for AED-induced teratogenicity. The urea derivatives of three VPA constitutional isomers propylisopropylacetylurea, diisopropylacetylurea, and 2-ethyl-3-methyl-pentanoylurea displayed a broad spectrum of anticonvulsant activity in rats with a clear superiority over their corresponding amides and acids. Enanatiomers of propylisopropylacetylurea and propylisopropylacetamide revealed enantioselective anticonvulsant activity, whereas only enantiomers of propylisopropylacetylurea displayed enantioselective teratogenicity. These potent urea derivatives caused neural tube defects, but only at doses markedly exceeding their effective dose, whereas VPA showed no separation between its anticonvulsant activity and teratogenicity. The broad spectrum of anticonvulsant activity of the urea derivatives coupled with their wide safety margin make them potential candidates to become new, potent AEDs.
- Shimshoni, Jakob Avi,Bialer, Meir,Wlodarczyk, Bogdan,Finnell, Richard H.,Yagen, Boris
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- Assessment of intermolecular N-H.F and N-H.Cl hydrogen bonding in stabilising hetero- and homodimers in solution
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This paper describes the first assessment of intermolecular weak N-H.F and N-H.Cl hydrogen bonding in stabilising hetero- and homodimers in solution. Aromatic amide and urea monomers have been designed and synthesised. The association constants of the heterodimers formed by two complementary monomers and the homodimers formed by self-complementary monomers have been determined by using 1H titration and dilution experiments. The results show that both N-H.F and N-H.Cl hydrogen bonds are able to stabilise the corresponding dimers to a measurable extent, even though the stability of the dimers is generally low.
- Liu, Yan-Hua,Xu, Xiao-Na,Zhao, Xin,Li, Zhan-Ting
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- Copper-Catalyzed Bromination of C(sp3)?H Bonds Distal to Functional Groups
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Selective bromination of γ-methylene C(sp3)?H bonds of aliphatic amides and δ-methylene C(sp3)?H bonds of nosyl-protected alkyl amines are developed using NBS as the brominating reagent and catalytic amount of CuII/phenanthroline complexes as the catalyst. Aryl and benzylic C?H bonds at other locations remain intact during this directed radical abstraction reaction.
- Liu, Tao,Myers, Michael C.,Yu, Jin-Quan
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- Polymorphism in 'L' shaped lipids: structure of N-, O-diacylethanolamines with mixed acyl chains
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Although solid state polymorphism in lipids has been established by spectroscopic and calorimetric studies long ago, only in a few cases crystal structures of different polymorphs of the same compound have been reported, possibly due to difficulties in obtaining high quality single crystals of individual polymorphs. Recent studies show that N-, O-diacylethanolamines (DAEs) can be derived by the O-acylation of the stress-related lipids, the N-acylethanolamines under physiological conditions. In this study, two DAEs with mixed acyl chains, namely N-palmitoyl, O-octanoylethanolamine and N-palmitoyl, O-decanoylethanolamine have been synthesized and their three-dimensional structures were determined. Both the compounds were found to adopt 'L' shaped structures and exist in two polymorphic forms, α and β. In the α form a mixed-type chain packing has been observed whereas in the β form the chain packing is symmetric. Similar polymorphic forms are likely to exist in other 'L' shaped lipids such as 1,3-diacylglycerols and ceramides, where polymorphism has been detected earlier, but three-dimensional structures - which can give precise information about the packing at atomic resolution - have not been reported.
- Tarafdar, Pradip K.,Swamy, Musti J.
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- Pyrene-derived novel one- and two-component organogelators
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A new class of alkyl-chainappended pyrene derivatives 4 - 14 were synthesized and evaluated for their gelation abilities. Depending on the nature of the linking group, these compounds gelated a number of organic solvents, either in the presence or in the absence of the acceptor molecule 2,4,7-trinitrofluorenone (TNF). Compounds with ester, ether, or alkyl linkages gelated a number of hydroxylic and hydrocarbon solvents by means of a charge-transfer interaction with TNF, while compounds with amide, urethane and urea linkers formed gels on their own in a variety of solvents by means of π-π stacking and hydrogen-bonding interactions. The X-ray crystal structure of urethane (S)-12 showed hydrogen-bonding and stacking features, as suggested by the model. The gels obtained were investigated by spectroscopic and electron microscopic techniques which provided structural insights.
- Babu,Sangeetha,Vijaykumar,Maitra, Uday,Rissanen, Kari,Raju
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- Effect of coaggregate formation on the fluorescence quenching of anthracene derivatives by m-N,N-diethyl-aminophenyl carboxylates with different chain lengths as quenchers
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In the dioxane-H2O system, electron-transfer quenching processes have been observed between the excited 9-anthrylmethyl esters of butyric acid (A-4), caprylic acid (A-8), lauric acid (A-12) and palmitic acid (A-16) as fluorescence probes, and m-N-N-diethylaminophenyl esters of butyric acid (P-4), caprylic acid (P-8) lauric acid (P-12) and palmitic acid (P-16) as quenchers. The results indicate that the hydrophobic-lipophibic interaction (HLI)-driven coaggregation of an acceptor and a donor can very effectively facilitate the electron-transfer quenching process between the excited acceptor (or donor) and the ground-state donor (or acceptor) after they become preassociated inside the coaggregate species. Furthermore, the extent of HLI-driven coaggregation (preassociation) between the acceptor aid the donor may be assessed from the slope B of the equation I0/I = A + B[Q]. The chain-length effect and the effect of solvent aggregating power were also observed. Copyright
- Shi, Ji-Liang,Qiu, Zhi-Hai,Jiang, Xi-Kui
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- 3-Aminobenzenesulfonamides incorporating acylthiourea moieties selectively inhibit the tumor-associated carbonic anhydrase isoform IX over the off-target isoforms I, II and IV
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We describe the synthesis of a series of novel 1-aroyl/acyl-3-(3-aminosulfonylphenyl) thioureas (4a–k) acting as human carbonic anhydrase (hCA, EC 4.2.1.1) inhibitors. Reaction of alkyl/aryl isothiocyanates with 3-aminobenzenesulfonamide afforded a series of the title compounds incorporating a variety of short as well as highly lipophilic long tails. The newly synthesized sulfonamides were evaluated against 4 physiologically relevant CA isoforms (hCA I, II, IV, and IX). Several compounds showed interesting inhibitory activity. The tumor-associated hCA IX was the most sensitive isoform to inhibition with these compounds, with KIs in the range of 21.5–44.0 nM and selectivity ratios over the major cytosolic isoform hCA II in the range of 3.35–37.3. The sulfonamides incorporating the phenylacetylthioureido and pentadecanoylthioureido moieties were the most hCA IX-selective inhibitors detected in this work, making them of interest for further investigations.
- Fattah, Tanzeela Abdul,Bua, Silvia,Saeed, Aamer,Shabir, Ghulam,Supuran, Claudiu T.
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- Pyrene-sensitized electron transport across vesicle bilayers: Dependence of transport efficiency on pyrene substituents
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Endoergic electron transport across vesicle bilayers from ascorbate (Asc-) in the inner waterpool to methylviologen (MV2+) in the outer aqueous solution was driven by the irradiation of pyrene derivatives embedded in the vesicle bilayers. The initial rate of MV2+ reduction is dependent on the substituent group of the pyrenyl ring; a hydrophilic functional group linked with the pyrenyl ring by a short methylene chain acts as a sensitizer for the electron transport. Mechanistic studies using (1-pyrenyl)alkanoic acids (1a-c) as sensitizers suggest that the electron transport is mainly initiated by the reductive quenching of the singlet excited state of the pyrene by Asc- and proceeds by a mechanism involving electron exchange between the pyrenes located at the inner and outer interface across the vesicle bilayer. We designed and synthesized novel unsymmetrically substituted pyrenes having both a hydrophilic group linked by a short methylene chain and a hydrophobic long alkyl group (5a-c), which acted as excellent sensitizers for the electron transport across vesicle bilayers. The Royal Society of Chemistry 2006.
- Mizushima, Tadashi,Yoshida, Asako,Harada, Akitomo,Yoneda, Yu,Minatani, Tomiaki,Murata, Shigeru
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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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- Synthesis of a Gemcitabine Prodrug for Remote Loading into Liposomes and Improved Therapeutic Effect
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The chemotherapeutic gemcitabine was actively and stably loaded into lipid nanoparticles through the formation of a prodrug. Gemcitabine was chemically modified to increase the lipophilicity and introduce a weak base moiety for remote loading. Several derivatives were synthesized and screened for their potential to be good liposomal drug candidates for remote loading by studying their solubility, stability, cytotoxicity, and loading efficiency. Two morpholino derivatives of GEM (22 and 23) were chosen as the preferred prodrugs for this purpose as they possessed the best loading efficiencies (100% for drug-to-lipid ratio of 0.36 w/w). This is a considerable improvement over a passive loading strategy where typical loading efficiencies are on the order of ～10-20% for a drug-to-lipid ratio of ～0.01. Liposomes loaded with these two prodrugs were studied in an s.c. tumor model in vivo and showed improved therapeutic effect over free GEM (～2-fold) and saline control (8- to 10-fold). This work demonstrates how chemical modification of a known hydrophilic drug can lead to improved loading, stability, and drug delivery in vivo.
- May, Jonathan P.,Undzys, Elijus,Roy, Aniruddha,Li, Shyh-Dar
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- Design, synthesis, and cholesterol-lowering efficacy for prodrugs of berberrubine
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In order to enhance oral bioavailability of berberine (BBR) for its cholesterol-lowering efficacy in vivo, a series of ester or ether prodrugs of berberrubine (M1), which is an active metabolite of BBR after first-pass metabolism, were designed, semi-synthesized, and evaluated. Among these M1 prodrugs, compound 5g possessing palmitate at the 9-position showed a moderate Log P value and esterase hydrolysis rate for releasing M1 in blood. Its cholesterol-lowering efficacy in vivo was evaluated in hyperlipidemic SD rats. Compound 5g (100 mg/kg/d) reduced blood CHO and LDL-c by 35.8% and 45.5%, respectively, similar to that by BBR. It also exhibited a good safety in rats with no side-effect on liver and kidney function. Therefore, the design of M1 prodrug appears to be an effective strategy to improve pharmacokinetic feature of BBR for its lipid-lowering efficacy in vivo.
- Li, Ying-Hong,Li, Yi,Yang, Peng,Kong, Wei-Jia,You, Xue-Fu,Ren, Gang,Deng, Hong-Bin,Wang, Yue-Ming,Wang, Yan-Xiang,Jiang, Jian-Dong,Song, Dan-Qing
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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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- Premating behavior of Bombus confusus males and analysis of their labial gland secretion
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Premating behavior in the bumblebee Bombus confusus was studied. Visual searching for females is not the only premating strategy of this species, as was believed earlier. Males of B. confusus have a normally developed labial gland and its secretion is used to mark a perch from which they visually search for females. The labial gland secretion contains geranylcitronellol and (Z)-9-octadecenyl acetate as the main components.
- Hovorka, Oldrich,Urbanova, Klara,Valterova, Irena
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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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- Lipophilic quinolone derivatives: Synthesis and in vitro antibacterial evaluation
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This paper reports on the design of a series of 10 novel lipophilic piperazinyl derivatives of the 1-cyclopropyl-6-fluoro-8-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid, their synthesis, their characterisation by 1H, 13C and 19F NMR, IR spectroscopy and HRMS, as well as their biological activity against bacteria of medical interest. Among these derivatives, 2 were as potent as the parent quinolone against Neisseria gonorrhoeae whereas all the compounds displayed lower activity than the parent quinolone against other bacteria of medical interest. Our results showing that the increased lipophilicity was deleterious for antibacterial activity may help to design new quinolone derivatives in the future, especially lipophilic quinolones which have been poorly investigated previously.
- Sadowski, Elodie,Bercot, Beatrice,Chauffour, Aurélie,Gomez, Catherine,Varon, Emmanuelle,Mainardis, Mary,Sougakoff, Wladimir,Mayer, Claudine,Sachon, Emmanuelle,Anquetin, Guillaume,Aubry, Alexandra
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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 0023-0037
(2020/10/20)
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- Carbon dots as photocatalysts for organic synthesis: Metal-free methylene-oxygen-bond photocleavage
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We report for the first time that irradiation of four different citric acid-derived carbon dots (CDs), in the absence of any other redox mediators, promotes an organic reaction. In this proof-of-concept study methylene-oxygen bond reductive photocleavage in N-methyl-4-picolinium esters is demonstrated. Cyclic voltammetry and UV-Vis spectra of the CDs and of the esters indicate that photocleavage reactivity correlates with the redox properties and the relative energies expressed in the Fermi scale. A photo-fragmentation mechanism is proposed. This study offers a new possibility to employ inexpensive and readily available CDs to promote photo-organic reactions.
- Cailotto, Simone,Negrato, Matteo,Daniele, Salvatore,Luque, Rafael,Selva, Maurizio,Amadio, Emanuele,Perosa, Alvise
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supporting information
p. 1145 - 1149
(2020/03/11)
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- Synthesis and anticancer evaluation of new lipophilic 1,2,4 and 1,3,4-oxadiazoles
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A series of1,2,4- and 1,3,4-oxadiazole derivatives were synthesized and evaluated for their anticancer activity. Halogenated 1,2,4-oxadiazoles were obtained from benzonitrile and coupled either lipophilic amines or with aminoalcohols. Lipophilic 1,3,4-oxadiazole derivatives were obtained through the Mannich reactions between 5-(aryl)-1,3,4-oxadiazole-2-thiol and alkylated or acylated amines. The in vitro cytotoxic effects were evaluated against 4T1– mammary carcinoma and CT26 – colon cancer cells. The best results were obtained for the 1,3,4-oxadiazole coupled to alkylated piperazine with 10–14 carbon chain moiety, with IC50 values ranging from 1.6 to 3.55μΜ for the 4T1 cell line, and from 1.6 to 3.9 μM for the CT26.WT cell line, and selectivity index up to 19. The most potent compounds were investigated with AnnexinV and PI staining as indicative of apoptosis induction.
- Caneschi, Wiliam,Enes, Karine Braga,Carvalho de Mendon?a, Camille,de Souza Fernandes, Fábio,Miguel, Fabio Balbino,da Silva Martins, Jefferson,Le Hyaric, Mireille,Pinho, Roberto Rosas,Duarte, Lucas Mattos,Leal de Oliveira, Marcone Augusto,Dos Santos, Hélio F.,Paz Lopes, Miriam Teresa,Dittz, Dalton,Silva, Heveline,Costa Couri, Mara Rubia
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- COMPOSITIONS AND METHODS FOR THE TREATMENT OF IRRITABLE BOWEL SYNDROME
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The disclosures herein provide compounds of formula I, formula II, formula III, formula IV, formula V, formula VI, formula VII, formula VIII, formula IX, formula X, formula XI, formula XII, formula XIII, formula XIV and formula XV or its pharmaceutical acceptable salts, as well as polymorphs, enantiomers, stereoisomers, solvates, and hydrates thereof. These salts may be formulated as pharmaceutical compositions. The pharmaceutical compositions may be formulated for oral administration, suppository, transdermal, buccal, rectal, topical, transdermal, transmucosal, intravenous, parenteral administration, syrup, or injection. Such compositions may be used to treatment of irritable bowel syndrome (IBS), inflammatory bowel diseases or its associated complications.
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Page/Page column 00130; 00132
(2018/03/06)
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- Ferric(III) Chloride Catalyzed Halogenation Reaction of Alcohols and Carboxylic Acids Using α,α-Dichlorodiphenylmethane
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A new method for chlorination of alcohols and carboxylic acids, using α,α-dichlorodiphenylmethane as the chlorinating agent and FeCl3 as the catalyst, was developed. The method enables conversions of various alcohols and carboxylic acids to their corresponding alkyl and acyl chlorides in high yields under mild conditions. Particulary interesting is the observation that the respective alkyl bromides and iodides can be generated from alcohols when either LiBr or LiI are present in the reaction mixtures.
- Lee, Chang-Hee,Lee, Soo-Min,Min, Byul-Hana,Kim, Dong-Su,Jun, Chul-Ho
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supporting information
p. 2468 - 2471
(2018/04/25)
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- IONIZABLE CATIONIC LIPID FOR RNA DELIVERY
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What is described is a compound of formula I consisting of a compound in which R1 is a branched chain alkyl consisting of 10 to 31 carbons; R2 is a linear alkyl, alkenyl, or alkynyl consisting of 2 to 20 carbons; L1 and L2 are the same or different, each a linear alkylene of 1 to 20 carbons or a linear alkenylene of 2 to 20 carbons; X1 is S or O; R3 is a linear or branched alkylene consisting of 1 to 6 carbons; and R4 and R5 are the same or different, each a hydrogen or a linear or branched alkyl consisting of 1 to 6 carbons; or a pharmaceutically acceptable salt thereof.
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Paragraph 0020; 0185; 0186; 0413
(2018/07/04)
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- Discovery of long-chain salicylketoxime derivatives as monoacylglycerol lipase (MAGL) inhibitors
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Monoacylglycerol lipase (MAGL) is the enzyme hydrolyzing the endocannabinoid 2-arachidonoylglycerol (2-AG) to free arachidonic acid and glycerol. Therefore, MAGL is implicated in many physiological processes involving the regulation of the endocannabinoid system and eicosanoid network. MAGL inhibition represents a potential therapeutic target for many diseases, including cancer. Nowadays, most MAGL inhibitors inhibit this enzyme by an irreversible mechanism of action, potentially leading to unwanted side effects from chronic treatment. Herein, we report the discovery of long-chain salicylketoxime derivatives as potent and reversible MAGL inhibitors. The compounds herein described are characterized by a good target selectivity for MAGL and by antiproliferative activities against a series of cancer cell lines. Finally, modeling studies suggest a reasonable hypothetical binding mode for this class of compounds.
- Bononi, Giulia,Granchi, Carlotta,Lapillo, Margherita,Giannotti, Massimiliano,Nieri, Daniela,Fortunato, Serena,Boustani, Maguie El,Caligiuri, Isabella,Poli, Giulio,Carlson, Kathryn E.,Kim, Sung Hoon,Macchia, Marco,Martinelli, Adriano,Rizzolio, Flavio,Chicca, Andrea,Katzenellenbogen, John A.,Minutolo, Filippo,Tuccinardi, Tiziano
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p. 817 - 836
(2018/08/24)
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- Synthesis and biological evaluation of 5-fatty-acylamido-1, 3, 4-thiadiazole-2-thioglycosides
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In the present study, the synthesis of 1, 3, 4-thiadiazole-based thioglycosides were accomplished in good yields with employing a convergent synthetic route. The starting material 5-amino-1, 3, 4-thiadiazole-2-thiol and followed by a series of 5-fatty-acylamido-1, 3, 4-thiadiazole-2-thiols (4a–4j) were synthesized with different fatty acid chlorides. The glycosylation of compounds 4a–4j were achieved with trichloroacetimidate methodology. Antimicrobial and cytotoxicity activities of title compounds were evaluated. Among the entire compounds lauric acid and myristic acid derivatives showed good and moderate antimicrobial activity. In case of cytotoxicity results of compounds 8a–8j and 9a–9j, the acetate protected short chain (C6:0, C8:0, C10:0) compounds and the free hydroxyl long chain saturated (C16:0, C18:0) and unsaturated (C18:1, C22:1) compounds exhibited good activity against different cancer cell lines. Further, the free hydroxyl compounds 9a, 9c–9j did not show any toxicity towards normal CHO-K1 cell line whereas acylated compounds 8a–8j exhibited toxicity.
- Vudhgiri, Srikanth,Koude, Dhevendar,Veeragoni, Dileep Kumar,Misra, Sunil,Prasad,Jala, Ram Chandra Reddy
-
supporting information
p. 3370 - 3373
(2017/07/07)
-
- CHEMICAL MODULATORS OF IMMUNE CHECKPOINTS AND THERAPEUTIC USE
-
Compounds and pharmaceutical compositions that down-regulate immune checkpoints such as PD-1, PD-L1 and CTLA-4 are provided. Also provided are methods of treating a disease by down-regulating immune checkpoints such as PD-1, PD-L1 and CTLA-4. The methods
- -
-
Paragraph 0237-0238
(2017/07/29)
-
- Synthesis, pH dependent, plasma and enzymatic stability of bergenin prodrugs for potential use against rheumatoid arthritis
-
Bergenin is a unique C-glycoside natural product possessing anti-inflammatory and anti-arthritic activity. It is hydrophilic molecule and stable under acidic conditions however is unstable at neutral-basic pH conditions. The rate of degradation is directly proportional to the increase in pH which might be one of the reasons for its low oral bioavailability. Thus, herein our objective was to improve its stability using prodrug strategy. Various ester and ether prodrugs were synthesized and studied for lipophilicity, chemical stability and enzymatic hydrolysis in plasma/esterase. The stability of synthesized prodrugs was evaluated in buffers at different pH, in biorelevant media such as SGF, SIF, rat plasma and in esterase enzyme. All prodrugs displayed significantly improved lipophilicity compared with bergenin, which was in accordance with the criteria of drug-like compounds. Acetyl ester 4a2 appeared to be the most promising prodrug as it remained stable at gastric/intestinal pH and was completely transformed to the parent compound bergenin in plasma as desired for an ideal prodrug. The data presented herein, will help in designing stable prodrugs of unstable molecules with desired physicochemical properties in structurally similar chemotypes.
- Singh, Rohit,Kumar, Vikas,Bharate, Sonali S.,Vishwakarma, Ram A.
-
p. 5513 - 5521
(2017/10/06)
-
- Citronellol fatty acid ester derivative and application and preparation method thereof
-
The invention relates to a citronellol fatty acid ester derivative and an application and preparation method thereof. The citronellol fatty acid ester derivative is used as a transdermal absorption penetration enhancer for application and used for preparing a transdermal drug delivery preparation so that transdermal absorption of drugs can be improved, and the accumulative penetration amount of the drugs is increased. According to the citronellol fatty acid ester derivative, after reaction with thionyl chloride, fatty acyl chloride is prepared, then the fatty acyl chloride reacts with citronellol, and the citronellol fatty acid ester derivative is obtained. The citronellol fatty acid ester derivative can be applied to the transdermal drug delivery preparation, improves the penetration ability of the drugs, and can also be used as spice to mask the objectionable odor of the preparation.
- -
-
Paragraph 0049; 0050
(2017/12/09)
-
- Nerol aliphatic ester derivative as well as application and preparation method thereof
-
The invention belongs to the technical field of medicine, and relates to a nerol aliphatic ester derivative as well as application and a preparation method thereof. The nerol aliphatic ester is obtained by a esterification reaction between nerol and straight-chain fatty acid and is prepared from the following steps: preparing acyl chloride by reaction between fatty acid and sulfoxide chloride; preparing nerol aliphatic ester. by reaction between acyl chloride and nerol. The nerol aliphatic ester can be used as a penetration enhancer to be applied to external preparation, such as a patch, a cataplasm, an ointment, a gelling agent and a spraying agent, so that the percutaneous absorption of medicine is improved. The nerol aliphatic ester is a good percutaneous absorption enhancer and has a wide application prospect.
- -
-
Paragraph 0047; 0048
(2017/11/04)
-
- Lavandulol fatty acid ester derivative, application and preparation method thereof
-
The invention relates to a derivative, application and a preparation method of the derivative, in particular to a lavandulol fatty acid ester derivative, application and a preparation method thereof. The lavandulol fatty acid ester derivative is prepared by preparing fatty acyl chloride and then carrying out reaction with lavandulol. The lavandulol fatty acid ester derivative can be applied as a transdermal absorption penetration enhancer to prepare transdermal drug delivery preparations, and can improve transdermal absorption of drugs and increase the cumulative penetration amount of drugs. The compound provided by the invention can be applied to transdermal drug delivery preparations to strengthen the penetration performance of drugs, and also can be used as lavender alcohol fatty acid ester derivative, and its application and preparation method. Lavender fatty acid ester derivatives are prepared by preparing fatty acyl chloride and then reacting with lavender. As a percutaneous absorption and penetration enhancer, the transdermal drug preparation is prepared to improve the absorption of the drug and increase the cumulative permeation of the drug. The compounds described in the present invention can be used in the percutaneous drug delivery, enhance the permeation ability of the drug, and can also be used as a spice to cover up the objectionable odor of preparations.
- -
-
Paragraph 0006; 0007; 0048; 0049
(2017/12/27)
-
- Eugenol fatty acid ester derivative as well as application and preparation method thereof
-
The invention discloses a eugenol fatty acid ester derivative as well as application and a preparation method thereof. Eugenol fatty acid ester is obtained by an esterification reaction of eugenol and straight-chain fatty acid. The method comprises the following steps: firstly, preparing acyl chlorine by reacting fatty acid with thionyl chloride; mixing eugenol with an equal mole amount of pyridine or triethylamine; then, dropwise adding the prepared acyl chloride under the cooling action of an ice bath to generate the eugenol fatty acid ester. Eugenol ester can be applied to external preparations such as patches, cataplasm, ointments, gels and spray agents as a penetration enhancer in order to increase the transdermal absorption amount of medicaments, is a very good percutaneous absorption penetration enhancer, and has a wide application prospect.
- -
-
Paragraph 0050-0051
(2017/11/18)
-
- Compositions and methods for the treatment of inflammatory bowel disease
-
The invention relates to the compounds of formula I and formula II or its pharmaceutical acceptable salts, as well as polymorphs, solvates, enantiomers, stereoisomers and hydrates thereof. The pharmaceutical compositions comprising an effective amount of compounds of formula I or formula II; and methods for treating or preventing inflammatory bowel disease may be formulated for oral, buccal, rectal, topical, transdermal, transmucosal, intravenous, parenteral administration, syrup, or injection. Such compositions may be used to treatment of gastrointestinal diseases and inflammation such as inflammatory bowel disease, ulcerative colitis, mild-to-moderate Crohn's disease, rheumatoid arthritis, inflammatory arthritis, psoriatic arthritis, liver cirrhosis and idiopathic urticaria.
- -
-
Page/Page column 51; 52; 55; 56
(2016/12/16)
-
- Α-terpineol fatty acid ester derivatives and use
-
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.
- -
-
Paragraph 0049; 0050
(2017/03/18)
-
- COMPOSITIONS AND METHODS FOR THE TREATMENT OF INFLAMMATORY BOWEL DISEASE
-
The invention relates to the compounds of formula I and formula II or its pharmaceutical acceptable salts, as well as polymorphs, solvates, enantiomers, stereoisomers and hydrates thereof. The pharmaceutical compositions comprising an effective amount of compounds of formula I or formula II; and methods for treating or preventing inflammatory bowel disease may be formulated for oral, buccal, rectal, topical, transdermal, transmucosal, intravenous, parenteral administration, syrup, or injection. Such compositions may be used to treatment of gastrointestinal diseases and inflammation such as inflammatory bowel disease, ulcerative colitis, mild-to-moderate Crohn's disease, rheumatoid arthritis, inflammatory arthritis, psoriatic arthritis, liver cirrhosis and idiopathic urticaria.
- -
-
Paragraph 0159-0161
(2016/06/01)
-
- 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)
-
- Structure-activity studies of Wnt/β-catenin inhibition in the Niclosamide chemotype: Identification of derivatives with improved drug exposure
-
The Wnt signaling pathway plays a key role in regulation of organ development and tissue homeostasis. Dysregulated Wnt activity is one of the major underlying mechanisms responsible for many diseases including cancer. We previously reported the FDA-approved anthelmintic drug Niclosamide inhibits Wnt/β-catenin signaling and suppresses colon cancer cell growth in vitro and in vivo. Niclosamide is a multi-functional drug that possesses important biological activity in addition to inhibition of Wnt/β-catenin signaling. Here, we studied the SAR of Wnt signaling inhibition in the anilide and salicylamide region of Niclosamide. We found that the 4′-nitro substituent can be effectively replaced by trifluoromethyl or chlorine and that the potency of inhibition was dependent on the substitution pattern in the anilide ring. Non-anilide, N-methyl amides and reverse amide derivatives lost significant potency, while acylated salicylamide derivatives inhibited signaling with potency similar to non-acyl derivatives. Niclosamide's low systemic exposure when dosed orally may hinder its use to treat systemic disease. To overcome this limitation we identified an acyl derivative of Niclosamide, DK-520 (compound 32), that significantly increased both the plasma concentration and the duration of exposure of Niclosamide when dosed orally. The studies herein provide a medicinal chemical foundation to improve the pharmacokinetic exposure of Niclosamide and Wnt-signaling inhibitors based on the Niclosamide chemotype. The identification of novel derivatives of Niclosamide that metabolize to Niclosamide and increase its drug exposure may provide important research tools for in vivo studies and provide drug candidates for treating cancers with dysregulated Wnt signaling including drug-resistant cancers. Moreover, since Niclosamide is a multi-functional drug, new research tools such as DK520 could directly result in novel treatments against bacterial and viral infection, lupus, and metabolic diseases such as type II diabetes, NASH and NAFLD.
- Mook, Robert A.,Wang, Jiangbo,Ren, Xiu-Rong,Chen, Minyong,Spasojevic, Ivan,Barak, Larry S.,Lyerly, H. Kim,Chen, Wei
-
supporting information
p. 5829 - 5838
(2015/11/11)
-
- Towards New Oligomesogenic Phosphonic Acids as Stabilizers of Nanoparticles Colloids in Nematic Liquid Crystals
-
Several synthetic strategies for the construction of linear and branched oligomesogenic phosphonic acids are examined, which differ in the method of building the key bimesogen unit. An efficient synthetic approach to the most promising compounds employs regioselective Kumada cross-coupling between [11-(4′-pentylbiphenyl-4-yl)undecyl]magnesium bromide and 4-(11-bromoundecyl)-4′-iodobiphenyl as the key step. Preliminary studies on the ability of the new ligands to stabilize nanoparticles colloids in nematic liquid crystals are undertaken for the example of quantum dots.
- Prodanov, Maksym F.,Diakov, Maksym Y.,Vlasenko, Ganna S.,Vashchenko, Valerii V.
-
supporting information
p. 1905 - 1910
(2015/08/06)
-
- Agent having neurotrophic factor-like activity
-
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 0045-0046
(2016/01/25)
-
- Method of manufacturing imidoyl diazidosulfochloride compd. various compd. and manufacturing method of using the same
-
PROBLEM TO BE SOLVED: To provide a new production method for synthesizing an imidoyl chloride compound dispensing with chlorination agents having poor handleability, to provide a method for producing various compounds in high yield and purity by using the imidoyl chloride compound, and to provide a method for isolating the imidoyl chloride compound in high efficiency and purity from a mixture of the imidoyl chloride compound and a phthalic anhydride compound.SOLUTION: The method for producing the imidoyl chloride compound comprises reaction of a specific amide compound with a specific phthaloyl chloride compound to produce a specific imidoyl chloride compound.
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-
Paragraph 0038
(2016/12/16)
-
- Antifungal agent, antimildew method using the same, and a method using the growth inhibiting growth inhibiting agent
-
PROBLEM TO BE SOLVED: To provide a mould-proofing agent exhibiting highly mould-proofing effect and enabling its own production cost to be reduced, and to provide a mould-proofing method using the same.SOLUTION: The mould-proofing agent is provided, which includes an amide compound represented by general formula (1) as an active ingredient. In general formula (1), either one of Xand Xis 3-7C branched alkyl, the other being H; alternatively, the Xand Xare optionally bound to each other to form a (substituted) saturated or unsaturated 5- or 6-membered ring; Y is a 4-7C alkylene group; and Z is methyl or vinyl.
- -
-
Paragraph 0116; 0123
(2017/01/02)
-
- Antiphlogistic enteropathy and method for treating dermatopathy compsn.
-
The invention relates to the compounds of formula I and formula II or its pharmaceutical acceptable salts, as well as polymorphs, solvates, enantiomers, stereoisomers and hydrates thereof. The pharmaceutical compositions comprising an effective amount of compounds of formula I or formula II; and methods for treating or preventing inflammatory bowel disease may be formulated for oral, buccal, rectal, topical, transdermal, transmucosal, intravenous, parenteral administration, syrup, or injection. Such compositions may be used to treatment of gastrointestinal diseases and inflammation such as inflammatory bowel disease, ulcerative colitis, mild-to-moderate Crohn's disease, rheumatoid arthritis, inflammatory arthritis, psoriatic arthritis, liver cirrhosis and idiopathic urticaria.
- -
-
Paragraph 0418; 0425; 0426
(2018/10/19)
-
- Synthesis of coenzyme A thioesters using methyl acyl phosphates in an aqueous medium
-
Regioselective S-acylation of coenzyme A (CoA) is achieved under aqueous conditions using various aliphatic and aromatic carboxylic acids activated as their methyl acyl phosphate monoesters. Unlike many hydrophobic activating groups, the anionic methyl acyl phosphate mixed anhydride is more compatible with aqueous solvents, making it useful for conducting acylation reactions in an aqueous medium.
- Pal, Mohan,Bearne, Stephen L.
-
supporting information
p. 9760 - 9763
(2015/01/08)
-
- Synthesis, characterization and biological evaluation of novel diesters of 4,4'-dihydroxy azoxy benzene with long chain carboxylic acids
-
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
-
p. 462 - 472
(2014/08/05)
-
- Structure and thermotropic phase behavior of a homologous series of n -Acylglycines: Neuroactive and antinociceptive constituents of biomembranes
-
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)
-
- Design and synthesis of epicocconone analogues with improved fluorescence properties
-
Epicocconone is a natural latent fluorophore that is widely used in biotechnology because of its large Stokes shift and lack of fluorescence in its unconjugated state. However, the low photostability and quantum yields of epicocconone have limited its wid
- Peixoto, Philippe A.,Boulang, Agathe,Ball, Malcolm,Naudin, Bertrand,Alle, Thibault,Cosette, Pascal,Karuso, Peter,Franck, Xavier
-
p. 15248 - 15256
(2014/12/11)
-
- Synthesis, antimycobacterial, antiviral, antimicrobial activity and QSAR studies of N2-acyl isonicotinic acid hydrazide derivatives
-
A series of N2-acyl isonicotinic acid hydrazides (1-17) was synthesized and tested for its in vitro antimycobacterial activity against Mycobacterium tuberculosis and the results indicated that the compound, isonicotinic acid N′- tetradecanoyl-hydrazide (12) was more active than the reference compound isoniazid. The results of antimicrobial activity of the synthesized compounds against S. aureus, B. subtilis, E. coli, C. albicans and A. niger indicated that compounds with dichloro, hydroxyl, tri-iodo and N 2 -tetradecanoyl substituent were the most active ones. The antiviral activity studies depicted that none of the tested compounds were active against DNA or RNA viruses. The multi-target QSAR model was found to be effective in describing the antimicrobial activity of N2-acyl isonicotinic acid hydrazides.
- Judge, Vikramjeet,Narasimhan, Balasubramanian,Ahuja, Munish,Sriram, Dharmarajan,Yogeeswari, Perumal,De Clercq, Erik,Pannecouque, Christophe,Balzarini, Jan
-
-
- Versatile synthesis of acylfuranones by reaction of acylketenes with α-hydroxy ketones: Application to the one-step multicomponent synthesis of cadiolide B and its analogues
-
Functionalized acylfuranones have been prepared in a one-step procedure by thermal fragmentation of the corresponding dioxinones in the presence of hydroxy ketones in basic conditions. Multicomponent reactions also occur on addition of an aldehyde as a third reaction partner resulting in an expeditious access to cadiolide B and its analogues. A new method for the synthesis of acylfuranones is described based on the fragmentation of dioxinones to acylketenes followed by trapping with hydroxy ketones. Addition of an aldehyde as a third reaction partner leads to a supplementary aldolization/crotonization sequence resulting in an expeditious synthesis of cadiolide B and its analogues. Copyright
- Peixoto, Philippe Alexandre,Boulange, Agathe,Leleu, Stephane,Franck, Xavier
-
p. 3316 - 3327
(2013/06/27)
-
- 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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p. 5886 - 5899
(2013/09/12)
-
- Chirality of the molecular assembly determined by intra-/inter-N- Ha?O hydrogen bonding in doubly substituted N-octanoylglyoxylic amides
-
N-Octanoylglyoxylic amides have been synthesized from N-octanoylisatins and their self-assembly analyzed in the solid state by X-ray crystallography. Of the seven compounds, only two utilize intramolecular N1-H1a?O2 hydrogen bonds, whereas five of them fo
- Suryanti, Venty,Bhadbhade, Mohan,Bishop, Roger,Black, David Stc.,Kumar, Naresh
-
p. 8446 - 8455
(2013/09/02)
-
- Direct conversion of N -alkoxyamides to carboxylic esters through tandem nbs-mediated oxidative homocoupling and thermal denitrogenation
-
Treatment of N-alkoxyamides with NBS in toluene was found to conveniently afford the corresponding carboxylic esters, including those bearing a bulky or long-chain substituent, in satisfactory to excellent yields. This approach not only represents a convenient and economic approach to a direct transformation of an alkoxyamide moiety into the carboxylic ester functional group, via oxidative homocoupling and the subsequent thermal denitrogenation, but also facilitates the synthesis of sterically hindered carboxylic esters.
- Zhang, Ningning,Yang, Rui,Zhang-Negrerie, Daisy,Du, Yunfei,Zhao, Kang
-
p. 8705 - 8711
(2013/09/24)
-
- Design and synthesis of conformationally restricted capsaicin analogues based in the 1, 3, 4-thiadiazoleheterocycle reveal a novel family of transient receptor potential vanilloid 1 (TRPV1) antagonists
-
4-hydroxy-3-methoxybenzaldehyde was used as starting material to obtain a number of 1, 3, 4-thiadiazole alkylamide derivatives. The pharmacological properties of these conformationally restricted capsaicin analogues were evaluated on HEK-293T cells transiently expressing TRPV1 receptor. By means of a highthroughput calcium imaging assay we find that 1, 3, 4-thiadiazoles (compounds 8-15) act as potent antagonists of the capsaicin receptor, inhibiting both, the capsaicin- and temperature-dependent activation. Docking studies suggested a different binding orientation on the vanilloid binding site when compared with capsaicin analogues, such as 5-iodononivamide. Overall, our studies suggest that 1, 3, 4-thiadiazoles interact with capsaicin 's binding region of the receptor, although using a different set of interactions within the vanilloid binding pocket.
- Rebolledo, Carolyne Lespay,Sotelo-Hitschfeld, Pamela,Brauchi, Sebastián,Olavarría, Miguel Zárraga
-
p. 193 - 203
(2013/10/01)
-
- New preparation method for Vilsmeier reagent and related imidoyl chlorides
-
An environmentally benign and inexpensive preparation method is described of some imidoyl chlorides, including the Vilsmeier reagent (VR), by using phthaloyl dichloride. Synthetic applications were demonstrated using the isolated VR or VR prepared in situ for the transformation of acids to acid chlorides, alcohols to chlorides, and the formylation of dimethylaminobenzene.
- Kimura, Yoshikazu,Matsuura, Daisuke,Hanawa, Takeshi,Kobayashi, Yukimoto
-
experimental part
p. 1116 - 1118
(2012/03/26)
-
- Total synthesis and allelopathic activity of cytosporones A-C
-
The search for efficient, environmentally friendly herbicides has been the focus of numerous studies on the organic synthesis of compounds isolated from natural sources. Cytosporones, which are phenolic lipids isolated from fungi, exhibit noteworthy biolo
- Zamberlam, Charles E. M.,Meza, Alisson,Leite, Carla Braga,Marques, Maria Rita,De Limaa, De?nis P.,Beatriz, Adilson
-
experimental part
p. 124 - 131
(2012/04/04)
-
- Analogs of 2-arachidonoylglycerin containing the no-donor group
-
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
-
p. 367 - 370
(2012/10/30)
-
- Inhibition of PCAF histone acetyltransferase and cytotoxic effect of N-acylanthranilic acids
-
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
-
p. 1379 - 1386
(2013/01/15)
-
- 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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- Growth inhibition of streptococcus from the oral cavity by α-Amyrin esters
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Five terpenoids were tested by the macrodilution broth method to determine their inhibition activity on cariogenic bacterial growth. In general, α-, β-amyrin and α-amyrin phenylacetate proved to be active, reducing the bacterial viability to less than 20%.
- Diaz-Ruiz, Gloria,Hernandez-Vazquez, Liliana,Luna, Hector,Del Carmen Wacher-Rodarte, Maria,Navarro-Ocana, Arturo
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p. 12603 - 12611
(2013/02/23)
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