title: Design, synthesis and antifungal activity of isosteric analogues of benzoheterocyclic N-myristoyltransferase inhibitors.
abstract: N-myristoyltransferase (NMT) has been a promising new target for the design of novel antifungal agents with new mode of action. A series of benzoxazole and indole derivatives were designed and synthesized as isosteric analogues of benzoheterocyclic NMT Inhibitors. In vitro antifungal assay indicated that the benzoxazole derivatives were far more potent than the indoles. Molecular docking studies revealed that the hydrogen bonding interaction between the benzoheterocyclic core and NMT might be essential in the orientation of the inhibitor to a proper position. The antifungal activity of benzoxazole derivative 8f was comparable or superior to that of fluconazole, which can serve as a good starting point for further studies of structural diversity of the benzoheterocyclic NMT inhibitors.
authors.affiliation: School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, PR China.
authors.forename: Chunquan
authors.initials: C
authors.lastname: Sheng
authors.forename: Hui
authors.initials: H
authors.lastname: Xu
authors.forename: Wenya
authors.initials: W
authors.lastname: Wang
authors.forename: Yongbing
authors.initials: Y
authors.lastname: Cao
authors.forename: Guoqiang
authors.initials: G
authors.lastname: Dong
authors.forename: Shengzheng
authors.initials: S
authors.lastname: Wang
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Che
authors.forename: Haitao
authors.initials: H
authors.lastname: Ji
authors.forename: Zhenyuan
authors.initials: Z
authors.lastname: Miao
authors.forename: Jianzhong
authors.initials: J
authors.lastname: Yao
authors.forename: Wannian
authors.initials: W
authors.lastname: Zhang
mesh_terms: D000217:Acyltransferases / Q000037:antagonists & inhibitors* / Q000737:chemistry; D000935:Antifungal Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D001583:Benzoxazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002176:Candida albicans / Q000187:drug effects / Q000201:enzymology; D020134:Catalytic Domain; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D008958:Models, Molecular; D013329:Structure-Activity Relationship
chemical_list: D000935:Antifungal Agents; D001583:Benzoxazoles; D004791:Enzyme Inhibitors; D007211:Indoles; D000217:Acyltransferases; C050480:glycylpeptide N-tetradecanoyltransferase