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Article Dans Une Revue Journal of Enzyme Inhibition and Medicinal Chemistry Année : 2020

Biological exploration of a novel 1,2,4-triazole-indole hybrid molecule as antifungal agent

Résumé

(2-(2,4-Dichlorophenyl)-3-(1H-indol-1-yl)-1-(1,2,4-1H-triazol-1-yl)propan-2-ol (8 g), a new 1,2,4-triazole-indole hybrid molecule, showed a broad-spectrum activity against Candida, particularly against low fluconazole-susceptible species. Its activity was higher than fluconazole and similar to voriconazole on C. glabrata (MIC90 = 0.25, 64 and 1 µg/mL, respectively), C. krusei (MIC90 = 0.125, 64 and 0.125 µg/mL, respectively) and C. albicans (MIC90 = 0.5, 8 and 0.25 µg/mL, respectively). The action mechanisms of 8 g were also identified as inhibition of ergosterol biosynthesis and phospholipase A2-like activity. At concentration as low as 4 ng/mL, 8g inhibited ergosterol production by 82% and induced production of 14a-methyl sterols, that is comparable to the results obtained with fluconazole at higher concentration. 8 g demonstrated moderate inhibitory effect on phospholipase A2-like activity being a putative virulence factor. Due to a low MRC5 cytotoxicity, this compound presents a high therapeutic index. These results pointed out that 8 g is a new lead antifungal candidate with potent ergosterol biosynthesis inhibition.

Dates et versions

hal-02455791 , version 1 (26-01-2020)

Identifiants

Citer

Fabrice Pagniez, Nicolas Lebouvier, Young Min Na, Isabelle Ourliac-Garnier, Carine Picot, et al.. Biological exploration of a novel 1,2,4-triazole-indole hybrid molecule as antifungal agent. Journal of Enzyme Inhibition and Medicinal Chemistry, 2020, 35 (1), pp.398-403. ⟨10.1080/14756366.2019.1705292⟩. ⟨hal-02455791⟩
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