Synthesis and biological evaluation of novel fluconazole analogues bearing 1,3,4-oxadiazole moiety as potent antifungal agents.
A novel series of fluconazole based mimics incorporating 1,3,4-oxadiazole moiety were designed and synthesized. All the title compounds were characterized by (1)H-NMR, (13)C-NMR, and Q-TOF-MS. Preliminary results revealed that most of analogues exhibited significant antifungal activity against seven pathogenic fungi. Compounds 9g and 9k (MIC80 ≤ 0.125 μg/mL, respectively) were found more potent than the positive controls itraconazole and fluconazole as broad-spectrum antifungal agents. The observed docking results showed that the 1,3,4-oxadiazole moiety enhanced the affinity binding to the cytochrome P450 14α-demethylase (CYP51).
Department of Organic Chemistry, College of Pharmacy, Second Military Medical University, Guohe Road 325, Shanghai, 200433, People's Republic of China.
Jun
J
Liao
Fan
F
Yang
Lei
L
Zhang
Xiaoyun
X
Chai
Qingjie
Q
Zhao
Shichong
S
Yu
Yan
Y
Zou
Qingguo
Q
Meng
Qiuye
Q
Wu
D000935:Antifungal Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001665:Binding Sites; D002176:Candida albicans / Q000187:drug effects; D004353:Drug Evaluation, Preclinical / Q000379:methods; D015725:Fluconazole / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology; D006801:Humans; D008826:Microbial Sensitivity Tests / Q000379:methods; D010069:Oxadiazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship
D000935:Antifungal Agents; D010069:Oxadiazoles; C583463:1,3,4-oxadiazole; D015725:Fluconazole