- Design, synthesis, biological evaluation and inhibition mechanism of 3-/4-alkoxy phenylethylidenethiosemicarbazides as new, potent and safe tyrosinase inhibitors
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Tyrosinase plays important roles in many different disease related processes, and the development of its inhibitors is particularly important in biotechnology. In this study, thirty-nine 3-/4-alkoxyphenylethyli-denethiosemicarbazides were synthesized as novel tyrosinase inhibitors based on structure-based molecular design. Our experimental results demonstrated that thirty-one of them possess remarkable tyrosinase inhibitory activities with IC50 value below 1μM, and 5a, 6e, 6g and 6t did not display any toxicity to 293T cell line at the concentration of 1000μmol/L. According to the inhibitory activities, several compounds were selected for detail investigation on the structure–activity relationships (SARs), mechanisms of enzyme inhibition, inhibitory kinetics and cytotoxicity. In particular, the interaction between the selected inhibitors and the active center of tyrosinase was considered and discussed in detail based on their structural characteristics. Taken together, the results presented here demonstrated that the newly designed compounds are promising candidates for the treatment of tyrosinase-related disorders and further development of them may have significant contribution in biomedical science.
- Liao, Bing,Mai, Yuliang,Shi, Huahong,Song, Senchuan,Wang, Fei
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p. 369 - 379
(2020/05/14)
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- Preparation method of micafungin derivative side chain intermediate
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The invention provides a preparation method of a micafungin derivative side chain intermediate. The method is a preparation method of the micafungin derivative side chain intermediate, and the micafungin derivative side chain intermediate is prepared by directly taking monoterephthalate as a raw material. The process route is greatly shortened, toxic and high-pollution noble metal catalysts are prevented from being prepared and used, impurities difficult to remove are prevented from being generated due to excessive reaction, the process is simple, few equipment is occupied, operation is easy and convenient, and the method is suitable for industrial application.
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Paragraph 0043-0044
(2020/02/14)
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- Synthesis and molecular docking studies of novel pyrimidine derivatives as potential antibacterial agents
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Abstract: The present work describes the in vitro antibacterial evaluation of some new pyrimidine derivatives. Twenty-two target compounds were designed, synthesized and preliminarily explored for their antimicrobial activities. The antimicrobial assay revealed that some target compounds exhibited significantly inhibitory efficiencies toward bacteria and fungal including drug-resistant pathogens. Compound 7c presented the most potent inhibitory activities against Gram-positive bacteria (e.g., Staphylococcus aureus 4220), Gram-negative bacteria (e.g., Escherichia coli 1924) and the fungus Candida albicans 7535, with an MIC of 2.4?μmol/L. Compound 7c was also the most potent, with MICs of 2.4 or 4.8?μmol/L against four multidrug-resistant, Gram-positive bacterial strains. The toxicity evaluation of the compounds 7c, 10a, 19d and 26b was assessed in human normal liver cells (L02 cells). Molecular docking simulation and analysis suggested that compound 7c has a good interaction with the active cavities of dihydrofolate reductase (DHFR). In vitro enzyme study implied that compound 7c also displayed DHFR inhibition. Graphic abstract: [Figure not available: see fulltext.]
- Bai, Xue-Qian,Li, Chun-Shi,Cui, Ming-Yue,Song, Ze-Wen,Zhou, Xing-Yu,Zhang, Chao,Zhao, Yang,Zhang, Tian-Yi,Jiang, Tie-Yan
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p. 1165 - 1176
(2019/12/11)
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- Design, synthesis, docking studies and monoamine oxidase inhibition of a small library of 1-acetyl- and 1-thiocarbamoyl-3,5-diphenyl-4,5-dihydro-(1h)-pyrazoles
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New N-acetyl/N-thiocarbamoylpyrazoline derivatives were designed and synthesized in high yields to assess their inhibitory activity and selectivity against human monoamine oxidase A and B. The most important chiral compounds were separated into their single enantiomers and tested. The impact of the substituents at N1, C3 and C5 positions as well the influence of the configuration of the C5 on the biological activity were analyzed. Bulky aromatic groups at C5 were not tolerated. p-Prenyloxyaryl moiety at C3 oriented the selectivity toward the B isoform. The results were also corroborated by molecular modelling studies providing new suggestions for the synthesis of privileged structures to serve as lead compounds for the treatment of mood disorders and neurodegenerative diseases.
- Guglielmi, Paolo,Carradori, Simone,Poli, Giulio,Secci, Daniela,Cirilli, Roberto,Rotondi, Giulia,Chimenti, Paola,Petzer, Anél,Petzer, Jacobus P.
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- Synthesis and liquid crystalline properties of a new homologous series of 4,5-disubstituted 2H-[1,2,3]-triazoles via azide-chalcone oxidative cycloaddition reaction
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A new homologous series of 4,5-disubstituted 2H-[1,2,3]-triazole derivatives were synthesized from chalcones and sodium azide via oxidative cycloaddition reaction; CuI was used as catalyst. Flexibility in the synthesized molecules was provided by attaching straight alkoxy chains. The synthesized compounds were characterized by elemental analysis, and 1HNMRand 13CNMRand LC-MS spectroscopies . The stability and range of the mesophases increased with the length of the chain on the triazoles. The melting point, transition temperatures, and enantiotropic liquid crystal morphologies were determined by differential scanning calorimetry (DSC) and polarizing optical microscopy (POM) equipped with a hot stage. Journal compilation
- Sowmya,Rai, K. M. Lokanatha
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p. 764 - 768
(2017/07/07)
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- Mechanochromic luminescent difluoroboron beta-diketonates
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The invention provides luminescent solid-state compositions comprising difluoroboron beta-diketonates wherein the compositions can exhibit mechanochromic luminescence. The mechanochromic effect on the luminescence can be reversible, such as thermally reversible. Various solid-state forms of the invention can have emission spectra that differ from the properties of the respective difluoroboron beta-diketonate in solution. The mechanochromic effect can be stimulated by pressure such as handwriting, and can be reversed over a period of minutes to hours at room temperature. The invention also provides methods of making and methods of using the solid-state compositions, such as for sensors and for information displays for use in biological sensing, and in art, design, and consumer products. Compositions of the invention, such as compositions in nanoparticulate form, or contained within a matrix material, can be used in conjunction with fluorescence microscopy to provide information concerning pressures and tensions within and external to living cells, tissues, or organisms.
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Page/Page column
(2015/07/15)
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- 3-Carboxamido-5-aryl-isoxazoles as new CB2 agonists for the treatment of colitis
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Recent investigations showed that anandamide, the main endogenous ligand of CB1 and CB2 cannabinoid receptors, possesses analgesic, antidepressant and anti-inflammatory effects. In the perspective to treat inflammatory bowel disease (IBD), our approach was to develop new selective CB2 receptor agonists without psychotropic side effects associated to CB1 receptors. In this purpose, a new series of 3-carboxamido-5- aryl-isoxazoles, never described previously as CB2 receptor agonists, was designed, synthesized and evaluated for their biological activity. The pharmacological results have identified great selective CB2 agonists with in vivo anti-inflammatory activity in a DSS-induced acute colitis mouse model.
- Tourteau, Aurélien,Andrzejak, Virginie,Body-Malapel, Mathilde,Lemaire, Lucas,Lemoine, Amélie,Mansouri, Roxane,Djouina, Madjid,Renault, Nicolas,El Bakali, Jamal,Desreumaux, Pierre,Muccioli, Giulio G.,Lambert, Didier M.,Chavatte, Philippe,Rigo, Beno?t,Leleu-Chavain, Natascha,Millet, Régis
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p. 5383 - 5394
(2013/09/02)
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- Highly efficient synthesis of phenols by copper-catalyzed hydroxylation of aryl iodides, bromides, and chlorides
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8-Hydroxyquinolin-N-oxide was found to be a very efficient ligand for the copper-catalyzed hydroxylation of aryl iodides, aryl bromides, or aryl chlorides under mild reaction conditions. This methodology provides a direct transformation of aryl halides to phenols and to alkyl aryl ethers. The inexpensive catalytic system showed great functional group tolerance and excellent selectivity.
- Yang, Kai,Li, Zheng,Wang, Zhaoyang,Yao, Zhiyi,Jiang, Sheng
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p. 4340 - 4343
(2011/10/08)
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- Alkyl chain length effects on solid-state difluoroboron β-diketonate mechanochromic luminescence
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Solid-state difluoroboron β-diketonate dyes display reversible mechanochromic luminescence (ML). To test the effects of alkyl chain length on solid state photoluminescence and ML, a series of dyes, BF2dbmOR, with dibenzoylmethane (dbm) ligands and alkoxyl substituents (-OR) were prepared, where R = CnH2n+1 and n = 1, 2, 3, 5, 6, 12, 14, 16, 18. Emission properties were investigated in solution and in the solid state. Fluorescence spectra and lifetimes were nearly identical for dyes in CH2Cl2 solution; whereas, in the solid state, as powders, thin films or spin cast films, emission maxima, and lifetimes were different among the samples. Solid-state ML emission spectra were monitored at room temperature as a function of time for smeared powders on quartz surfaces. The recovery time generally increased with alkyl chain length, ranging from minutes (n = 3) to days (n = 18). Longer chain analogues (n = 6, 12, 14, 16, 18) did not fully return to the original annealed emissive state even after months on quartz, though the dynamics are substrate dependent. Solid-state dyes were also investigated by XRD and DSC (powders), and by AFM (spin cast films).
- Nguyen, Nguyen D.,Zhang, Guoqing,Lu, Jiwei,Sherman, Arianna E.,Fraser, Cassandra L.
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supporting information
p. 8409 - 8415
(2013/01/11)
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- Lipopeptide Compounds and Their Use
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The present invention pertains generally to the field of therapeutic compounds, and more specifically to certain lipopeptide compounds comprising a cyclic peptide bearing a lipid side chain (for convenience, collectively referred to herein as “LP compounds”), which, inter alia, are antimicrobial, particularly antibacterial. The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to provide an antimicrobial function, particularly an antibacterial function, and in the treatment of diseases and conditions that are mediated by microbes, particularly bacteria, that are ameliorated by the antimicrobial function, particularly an antibacterial function, including bacterial diseases, optionally in combination with another agent, for example, another antibacterial agent.
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- Practical synthesis of FR195752, the side chain of Micafungin, utilizing a regioselective conversion of diaryl-β-diketone to 3,5-diarylisoxazole
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The practical synthesis of FR195752, the side chain of Micafungin, was established utilizing a highly regioselective conversion of diaryl-β- diketone to 3,5-diarylisoxazole via the corresponding β-keto enamine intermediate whose disfavored regioisomer could be recycled efficiently after its hydrolysis. In addition, the related substance of FR195752 could be strictly controlled by the purification of its intermediate.
- Ohigashi, Atsushi,Kanda, Atsushi,Tsuboi, Hiroyuki,Hashimoto, Norio
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p. 179 - 184
(2012/12/24)
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- Selectivity engineering of phase transfer catalyzed alkylation of 2′-hydroxyacetophenone: Enhancement in rates and selectivity by creation of a third liquid phase
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Enhancements in rate of reaction and selectivity of the desired product in biphasic reactions are achieved by creating a third liquid phase, under appropriate conditions, where the third liquid phase is the locale of the main reaction, having a dramatic effect on product distribution in complex chemical reactions. Thus, in the case of phase transfer catalysis (PTC), conversion of liquid-liquid (L-L) PTC into liquid-liquid-liquid (L-L-L) PTC is of considerable techno-commercial interest resulting in waste minimization which is a major theme of green chemistry. Etherification of 2′-hydroxyacetophenone with 1-bromopentane, under traditional liquid-liquid phase transfer catalysis, results in loss of catalyst. However, the transformation of two liquid phases into three liquid phases (L-L-L) PTC leads enhancement in rates by orders of magnitude, with 100% conversion of the limiting reactant 1-bromopentane and 100% selectivity to 2′-pentyloxyacetophenone. This strategy eliminates separation problems and results in high reaction rates reducing the total reaction time. Moreover, the catalyst-rich third phase is recycled more than 7 times without loss in activity. The kinetics of the reaction are studied in great detail. There is a substantial reduction in activation energy under L-L-L PTC vis-a-vis L-L PTC, where the locale of the reaction is shifted from the organic phase to the third phase.
- Yadav, Ganapati D.,Desai, Neesha M.
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p. 749 - 756
(2012/12/26)
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- Formulations for dyeing keratin fibers comprising a pyrazolotriazole coupler and oxidation base
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Formulations for the oxidation dyeing of keratin fibers comprising a coupler and oxidation base. The couplers are represented by the following structure: wherein: Z represents the elements of C, N, O, or S necessary to complete a substituted or unsubstituted heterocyclic 5 or 6 member ring along with nitrogen; R1represents a substituent group; and, X represents a hydrogen or a coupling off group.
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- Novel manufacturing method
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The present invention relates to a novel process for preparing of the compound of the following formula (I) Thus, the process for preparing of a compound of the formula (I): [Wherein R1 is carboxy or protected carboxy; R2 is lower alkoxy or higher alkoxy; A1 is divalent aromatic ring, divalent heterocyclic group or divalent cyclo(lower)alkane; and A2 is divalent aromatic ring, divalent heterocyclic group or divalent cyclo(lower)alkane], or a salt thereof, which comprises, reacting a compound of the formula (III): [Wherein R1, R2, A1 and A2 are each as defined above] or a salt thereof, with an acid ammonium salt to give a compound of the formula (II): [Wherein R1, R2, A1 and A2 are each as defined above] or a salt thereof, further reacting with hydroxylamine salt.
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