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

Authors :: Zhao S
Zhao L
Zhang X
Liu C
Hao C
Xie H
Sun B
Zhao D
Cheng M
Source :: European journal of medicinal chemistry [Eur J Med Chem] 2016 Nov 10; Vol. 123, pp. 514-522. Date of Electronic Publication: 2016 Jul 29.
Publication Year :: 2016
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.<br /> (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

Subjects :: Antifungal Agents chemistry
Antifungal Agents metabolism
Benzothiazoles chemistry
Benzothiazoles metabolism
Candida albicans drug effects
Catalytic Domain
Cryptococcus neoformans drug effects
Microbial Sensitivity Tests
Molecular Docking Simulation
Saccharomyces cerevisiae enzymology
Sterol 14-Demethylase chemistry
Sterol 14-Demethylase metabolism
Structure-Activity Relationship
Antifungal Agents chemical synthesis
Antifungal Agents pharmacology
Benzothiazoles chemical synthesis
Benzothiazoles pharmacology
Drug Design

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