Synthesis and antifungal activity of the novel azole compounds

KE Xuefeng; LI Jingzhe; FU Ben; LI Liangjing; CHAI Xiaoyun; WU Qiuye

doi:10.3969/j.issn.1006-0111.2017.01.006

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Objective To design and synthesize novel triazole antifungal derivatives with 1,3,4-oxadiazole side chain for the study of antifungal activities. Methods Fourteen title compounds were synthesized via acylation, aminolysis reaction, cyclization, nucleophilic substitution, etc. All the compounds were characterized by ¹H NMR, MS spectra. The in vitro antifungal activities were evaluated against six human pathogenic fungi through the micro-broth dilution method. Results The title compounds exhibited strong antifungal activities against all the tested fungi, especially against Candida albicans. Compounds 10d , 10i , 10l , and 10n were found to be the most effective, with a minimum inhibitory concentration(MIC₈₀) of 0.003 9 μg/ml.They are 16-fold more potent than ICZ (MIC₈₀ 0.062 5 μg/ml) and 64-fold more potent than FCZ (MIC₈₀ 0.25 μg/ml). Conclusion The 1,3,4-oxadiazole side chain could affect the antifungal activities. That could be due to the proper incorporation between the 1,3,4-oxadiazole substituted phenyl ring with the target enzyme.

Synthesis and antifungal activity of the novel azole compounds

1. Department of Organic Chemistry, School of Pharmacy, Second Military Medical University, Shanghai 200433, China

2. Department of Organic Chemistry, School of Pharmacy, Second Military Medical University, Shanghai 200433, China;Cadet Company 10 th, Student Brigade, Second Military Medical University, Shanghai 200433, China

Received Date: 2016-11-10

Rev Recd Date: 2016-12-21

Key words:

azole /
1,3,4-oxadiazole /
synthesis

Abstract: Objective To design and synthesize novel triazole antifungal derivatives with 1,3,4-oxadiazole side chain for the study of antifungal activities. Methods Fourteen title compounds were synthesized via acylation, aminolysis reaction, cyclization, nucleophilic substitution, etc. All the compounds were characterized by ¹H NMR, MS spectra. The in vitro antifungal activities were evaluated against six human pathogenic fungi through the micro-broth dilution method. Results The title compounds exhibited strong antifungal activities against all the tested fungi, especially against Candida albicans. Compounds 10d , 10i , 10l , and 10n were found to be the most effective, with a minimum inhibitory concentration(MIC₈₀) of 0.003 9 μg/ml.They are 16-fold more potent than ICZ (MIC₈₀ 0.062 5 μg/ml) and 64-fold more potent than FCZ (MIC₈₀ 0.25 μg/ml). Conclusion The 1,3,4-oxadiazole side chain could affect the antifungal activities. That could be due to the proper incorporation between the 1,3,4-oxadiazole substituted phenyl ring with the target enzyme.

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Synthesis and antifungal activity of the novel azole compounds

doi: 10.3969/j.issn.1006-0111.2017.01.006

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