Synthesis and biological evaluation of novel fluconazole analogues bearing 1,3,4-oxadiazole moiety as potent antifungal agents
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A novel series of fluconazole based mimics incorporating 1,3,4-oxadiazole moiety were designed and synthesized. All the title compounds were characterized by 1H-NMR, 13C-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).
KeywordsSynthesis Fluconazole Antifungal activity 1,3,4-Oxadiazole
This work was supported by the National Natural Science Foundation of China (No. 20772153) and Science & Technology Commission of Shanghai Municipality (09dZ1976700).
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