title: Discovery of highly potent triazole antifungal derivatives by heterocycle-benzene bioisosteric replacement.
abstract: On the basis of our previously discovered triazole antifungal lead compounds, heterocycle-benzene bioisosteric replacement was used to improve their pharmacokinetic profile. The designed new triazole derivatives have good antifungal activity toward a wide range of pathogenic fungi. Their binding mode with the target enzyme was clarified by molecular docking. The MIC value of the highly potent compound 8f against Candida albicans, Candida tropicalis, and Cryptococcus neoformans is 0.016 μg/mL, 0.004 μg/mL, and 0.016 μg/mL, respectively. Moreover, preliminary pharmacokinetic studies revealed that it showed improved oral absorption as compared to the lead compound iodiconazole and deserved for further evaluations.
authors: School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, People's Republic of China.
authors: Zhigan
authors: Z
authors: Jiang
authors: Yan
authors: Y
authors: Wang
authors: Wenya
authors: W
authors: Wang
authors: Shengzheng
authors: S
authors: Wang
authors: Bo
authors: B
authors: Xu
authors: Guorong
authors: G
authors: Fan
authors: Guoqiang
authors: G
authors: Dong
authors: Yang
authors: Y
authors: Liu
authors: Jianzhong
authors: J
authors: Yao
authors: Zhenyuan
authors: Z
authors: Miao
authors: Wannian
authors: W
authors: Zhang
authors: Chunquan
authors: C
authors: Sheng
mesh_terms: D000935:Antifungal Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001554:Benzene / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002176:Candida albicans / Q000187:drug effects; D041022:Candida tropicalis / Q000187:drug effects; D003455:Cryptococcus neoformans / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D055808:Drug Discovery; D006571:Heterocyclic Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000935:Antifungal Agents; D006571:Heterocyclic Compounds; D014230:Triazoles; D001554:Benzene