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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[1]	Nuccil M, Marr KA. Emerging fungal diseases[J]. Clin Infect Dis, 2005, 41(4):521-526.[2] Boschman CR, Bodnar UR, Tornatore MA, et al. Thirteen-year evolution of azole resistance in yeast isolates and prevalence of resistant strains carried by cancer patients at a large medical center[J]. Antimicrob Agents Chemother, 1998, 42(4):734-738.[3] 冷萍,郭秀丽,娄红祥.真菌耐药的分子机制及新型抗真菌药物[J].生理科学进展, 2005, 36(4):325-328.[4] Koltin Y, Hitchcock CA. Progress in the search for new triazole antifungal agents[J]. Curr Opin Chem Biol, 1997, 1(2):176-182.[5] Gallis HA, Drew RH, Pickard WW. Amphotericin B:30 years of clinical experience[J]. Rev Infect Dis,1990, 12(2):308-329.[6] Gallis HA. Amphotercin B:a commentary on its role as an antifungal agent and as a comparative agent in clinical trials[J]. Clin Infect Dis, 1996, 22(Suppl 2):S145-S147.[7] Li LJ, Ding H, Wang BG, et al. Synthesis and evaluation of novel azoles as potent antifungal agents[J]. Bioorg Med Chem Lett, 2014, 24(1):192-194.[8] National Committee for Clinical Laboratory Standards, Reference Method for Broth Dilution Antifungal Susceptibility Testing of Yeasts Approved standard[S]. Document M27-A2, National Committee for Clinical Laboratory Standards, Wayne, PA, 2002.[9] Chai XY, Zhang J, Hu HG, et al.Design, synthesis, and biological evaluation of novel triazole derivatives as inhibitors of cytochrome P45014α-demethylase[J]. Eur J Med Chem, 2009, 44(5):1913-1920.
[2]	Chai XY, Zhang J, Yu SC, et al. Design, synthesis, and biological evaluation of novel 1-(1H-1,2,4-triazole-1-yl)-2- (2,4-difluorophenyl)-3-substituted benzylamino-2-propanols[J]. Bioorg Med Chem Lett, 2009, 19(6):1811-1814.
[3]	Chai XY, Zhang J, Cao YB, et al.Design, synthesis and molecular docking studies of novel triazole as antifungal agent[J]. Eur J Med Chem, 2011, 46(7):3167-3176.
[4]	Chai XY, Yang G, Zhang J, et al. Synthesis and biological evaluation of triazole derivatives as potential antifungal agent[J]. Chem Biol Drug Des, 2012, 80(3):382-387.
[5]	Yu SC, Chai XY, Wang YW, et al. Triazole derivatives with improved in vitro antifungal activity over azole drugs[J]. Drug Des Devel Ther, 2014, 8:383-390.
[6]	Zou Y, Yu SC, Li RW, et al. Synthesis, antifungal activities and molecular docking studies of novel 2-(2,4-difluorophenyl) -2-hydroxy-3-(1H-1,2,4-triazol-1-yl)propyl dithiocarbamates[J]. Eur J Med Chem, 2014, 74(4):366-374.

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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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