Design, synthesis, and structure-activity relationship studies of benzothiazole derivatives as antifungal agents. 2016

Shizhen Zhao, and Liyu Zhao, and Xiangqian Zhang, and Chunchi Liu, and Chenzhou Hao, and Honglei Xie, and Bin Sun, and Dongmei Zhao, and Maosheng Cheng
Key Laboratory of Structure-Based Drug Design and Discovery, Ministry of Education, School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang 110016, PR China.

A series of compounds with benzothiazole and amide-imidazole scaffolds were designed and synthesized to combat the increasing incidence of drug-resistant fungal infections. The antifungal activity of these compounds was evaluated in vitro, and their structure-activity relationships (SARs) were evaluated. The synthesized compounds showed excellent inhibitory activity against Candida albicans and Cryptococcus neoformans. The most potent compounds 14o, 14p, and 14r exhibited potent activity, with minimum inhibitory concentration (MIC) values in the range of 0.125-2 μg/mL. Preliminary mechanism studies revealed that the compound 14p might act by inhibiting the CYP51 of Candida albicans. The SARs and binding mode established in this study are useful for further lead optimization.

UI MeSH Term Description Entries
D008826 Microbial Sensitivity Tests Any tests that demonstrate the relative efficacy of different chemotherapeutic agents against specific microorganisms (i.e., bacteria, fungi, viruses). Bacterial Sensitivity Tests,Drug Sensitivity Assay, Microbial,Minimum Inhibitory Concentration,Antibacterial Susceptibility Breakpoint Determination,Antibiogram,Antimicrobial Susceptibility Breakpoint Determination,Bacterial Sensitivity Test,Breakpoint Determination, Antibacterial Susceptibility,Breakpoint Determination, Antimicrobial Susceptibility,Fungal Drug Sensitivity Tests,Fungus Drug Sensitivity Tests,Sensitivity Test, Bacterial,Sensitivity Tests, Bacterial,Test, Bacterial Sensitivity,Tests, Bacterial Sensitivity,Viral Drug Sensitivity Tests,Virus Drug Sensitivity Tests,Antibiograms,Concentration, Minimum Inhibitory,Concentrations, Minimum Inhibitory,Inhibitory Concentration, Minimum,Inhibitory Concentrations, Minimum,Microbial Sensitivity Test,Minimum Inhibitory Concentrations,Sensitivity Test, Microbial,Sensitivity Tests, Microbial,Test, Microbial Sensitivity,Tests, Microbial Sensitivity
D002176 Candida albicans A unicellular budding fungus which is the principal pathogenic species causing CANDIDIASIS (moniliasis). Candida albicans var. stellatoidea,Candida stellatoidea,Dematium albicans,Monilia albicans,Myceloblastanon albicans,Mycotorula albicans,Parasaccharomyces albicans,Procandida albicans,Procandida stellatoidea,Saccharomyces albicans,Syringospora albicans
D003455 Cryptococcus neoformans A species of the fungus CRYPTOCOCCUS. Its teleomorph is Filobasidiella neoformans. Blastomyces neoformans,Debaryomyces neoformans,Filobasidiella neoformans,Lipomyces neoformans,Saccharomyces neoformans,Torula neoformans,Torulopsis neoformans,Cryptococcus neoformans var. grubii
D000935 Antifungal Agents Substances that destroy fungi by suppressing their ability to grow or reproduce. They differ from FUNGICIDES, INDUSTRIAL because they defend against fungi present in human or animal tissues. Anti-Fungal Agents,Antifungal Agent,Fungicides, Therapeutic,Antibiotics, Antifungal,Therapeutic Fungicides,Agent, Antifungal,Anti Fungal Agents,Antifungal Antibiotics
D012441 Saccharomyces cerevisiae A species of the genus SACCHAROMYCES, family Saccharomycetaceae, order Saccharomycetales, known as "baker's" or "brewer's" yeast. The dried form is used as a dietary supplement. Baker's Yeast,Brewer's Yeast,Candida robusta,S. cerevisiae,Saccharomyces capensis,Saccharomyces italicus,Saccharomyces oviformis,Saccharomyces uvarum var. melibiosus,Yeast, Baker's,Yeast, Brewer's,Baker Yeast,S cerevisiae,Baker's Yeasts,Yeast, Baker
D013329 Structure-Activity Relationship The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups. Relationship, Structure-Activity,Relationships, Structure-Activity,Structure Activity Relationship,Structure-Activity Relationships
D015195 Drug Design The molecular designing of drugs for specific purposes (such as DNA-binding, enzyme inhibition, anti-cancer efficacy, etc.) based on knowledge of molecular properties such as activity of functional groups, molecular geometry, and electronic structure, and also on information cataloged on analogous molecules. Drug design is generally computer-assisted molecular modeling and does not include PHARMACOKINETICS, dosage analysis, or drug administration analysis. Computer-Aided Drug Design,Computerized Drug Design,Drug Modeling,Pharmaceutical Design,Computer Aided Drug Design,Computer-Aided Drug Designs,Computerized Drug Designs,Design, Pharmaceutical,Drug Design, Computer-Aided,Drug Design, Computerized,Drug Designs,Drug Modelings,Pharmaceutical Designs
D052160 Benzothiazoles Compounds with a benzene ring fused to a thiazole ring.
D058886 Sterol 14-Demethylase An NADPH-dependent P450 enzyme that plays an essential role in the sterol biosynthetic pathway by catalyzing the demethylation of 14-methyl sterols such as lanosterol. The enzyme acts via the repeated hydroxylation of the 14-methyl group, resulting in its stepwise conversion into an alcohol, an aldehyde and then a carboxylate, which is removed as formic acid. Sterol 14-demethylase is an unusual cytochrome P450 enzyme in that it is found in a broad variety of organisms including ANIMALS; PLANTS; FUNGI; and protozoa. Sterol 14-Demethylases,CYP51 Cytochrome P-450,Cytochrome P-450 CYP51,Eburicol 14 alpha-Demethylase,Eburicol 14alpha-Demethylase,Lanosterol 14 alpha-Demethylase,Obtusifoliol 14alpha-Demethylase,Sterol 14-alpha-Demethylase,14 alpha-Demethylase, Eburicol,14 alpha-Demethylase, Lanosterol,14-Demethylase, Sterol,14-Demethylases, Sterol,14-alpha-Demethylase, Sterol,14alpha-Demethylase, Eburicol,14alpha-Demethylase, Obtusifoliol,CYP51 Cytochrome P 450,CYP51, Cytochrome P-450,Cytochrome P 450 CYP51,Cytochrome P-450, CYP51,Eburicol 14 alpha Demethylase,Eburicol 14alpha Demethylase,Lanosterol 14 alpha Demethylase,Obtusifoliol 14alpha Demethylase,P-450 CYP51, Cytochrome,P-450, CYP51 Cytochrome,Sterol 14 Demethylase,Sterol 14 Demethylases,Sterol 14 alpha Demethylase
D062105 Molecular Docking Simulation A computer simulation technique that is used to model the interaction between two molecules. Typically the docking simulation measures the interactions of a small molecule or ligand with a part of a larger molecule such as a protein. Molecular Docking,Molecular Docking Simulations,Molecular Docking Analysis,Analysis, Molecular Docking,Docking Analysis, Molecular,Docking Simulation, Molecular,Docking, Molecular,Molecular Docking Analyses,Molecular Dockings,Simulation, Molecular Docking

Related Publications

Shizhen Zhao, and Liyu Zhao, and Xiangqian Zhang, and Chunchi Liu, and Chenzhou Hao, and Honglei Xie, and Bin Sun, and Dongmei Zhao, and Maosheng Cheng
October 2021, Journal of agricultural and food chemistry,
Shizhen Zhao, and Liyu Zhao, and Xiangqian Zhang, and Chunchi Liu, and Chenzhou Hao, and Honglei Xie, and Bin Sun, and Dongmei Zhao, and Maosheng Cheng
January 2023, Molecules (Basel, Switzerland),
Shizhen Zhao, and Liyu Zhao, and Xiangqian Zhang, and Chunchi Liu, and Chenzhou Hao, and Honglei Xie, and Bin Sun, and Dongmei Zhao, and Maosheng Cheng
June 2023, Antibiotics (Basel, Switzerland),
Shizhen Zhao, and Liyu Zhao, and Xiangqian Zhang, and Chunchi Liu, and Chenzhou Hao, and Honglei Xie, and Bin Sun, and Dongmei Zhao, and Maosheng Cheng
August 2012, European journal of medicinal chemistry,
Shizhen Zhao, and Liyu Zhao, and Xiangqian Zhang, and Chunchi Liu, and Chenzhou Hao, and Honglei Xie, and Bin Sun, and Dongmei Zhao, and Maosheng Cheng
March 2014, International journal of molecular sciences,
Shizhen Zhao, and Liyu Zhao, and Xiangqian Zhang, and Chunchi Liu, and Chenzhou Hao, and Honglei Xie, and Bin Sun, and Dongmei Zhao, and Maosheng Cheng
August 2022, Molecules (Basel, Switzerland),
Shizhen Zhao, and Liyu Zhao, and Xiangqian Zhang, and Chunchi Liu, and Chenzhou Hao, and Honglei Xie, and Bin Sun, and Dongmei Zhao, and Maosheng Cheng
August 2018, The Journal of antibiotics,
Shizhen Zhao, and Liyu Zhao, and Xiangqian Zhang, and Chunchi Liu, and Chenzhou Hao, and Honglei Xie, and Bin Sun, and Dongmei Zhao, and Maosheng Cheng
August 2020, Bioorganic chemistry,
Shizhen Zhao, and Liyu Zhao, and Xiangqian Zhang, and Chunchi Liu, and Chenzhou Hao, and Honglei Xie, and Bin Sun, and Dongmei Zhao, and Maosheng Cheng
June 2014, Journal of medicinal chemistry,
Shizhen Zhao, and Liyu Zhao, and Xiangqian Zhang, and Chunchi Liu, and Chenzhou Hao, and Honglei Xie, and Bin Sun, and Dongmei Zhao, and Maosheng Cheng
March 2013, Journal of natural products,
Copied contents to your clipboard!