title: Design, synthesis, and structure-activity relationship studies of benzothiazole derivatives as antifungal agents.
abstract: 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.
authors: 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.
authors: Shizhen
authors: S
authors: Zhao
authors: 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.
authors: Liyu
authors: L
authors: Zhao
authors: 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.
authors: Xiangqian
authors: X
authors: Zhang
authors: 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.
authors: Chunchi
authors: C
authors: Liu
authors: 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.
authors: Chenzhou
authors: C
authors: Hao
authors: 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.
authors: Honglei
authors: H
authors: Xie
authors: Institute of BioPharmaceutical Research, Liaocheng University, 1 Hunan Road, Liaocheng 252000, PR China.
authors: Bin
authors: B
authors: Sun
authors: 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. Electronic address: medchemzhao@163.com.
authors: Dongmei
authors: D
authors: Zhao
authors: 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.
authors: Maosheng
authors: M
authors: Cheng
mesh_terms: D000935:Antifungal Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D052160:Benzothiazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D002176:Candida albicans / Q000187:drug effects; D020134:Catalytic Domain; D003455:Cryptococcus neoformans / Q000187:drug effects; D015195:Drug Design; D008826:Microbial Sensitivity Tests; D062105:Molecular Docking Simulation; D012441:Saccharomyces cerevisiae / Q000201:enzymology; D058886:Sterol 14-Demethylase / Q000737:chemistry / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D000935:Antifungal Agents; D052160:Benzothiazoles; D058886:Sterol 14-Demethylase
keywords: Antifungal activity; Azole antifungals; CYP51; Structure-activity relationship