In Vitro and In Silico Evaluations of the Antileishmanial Activities of New Benzimidazole-Triazole Derivatives
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Date
2023
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Abstract
Benzimidazole and triazole rings are important pharmacophores, known to exhibit various pharmacological activities in drug discovery. In this study, it was purposed to synthesize new benzimidazole-triazole derivatives and evaluate their antileishmanial activities. The targeted compounds (5a–5h) were obtained after five chemical reaction steps. The structures of the compounds were confirmed by spectral data. The possible in vitro antileishmanial activities of the synthesized compounds were evaluated against the Leishmania tropica strain. Further, molecular docking and dynamics were performed to identify the probable mechanism of activity of the test compounds. The findings revealed that compounds 5a, 5d, 5e, 5f, and 5h inhibited the growth of Leishmania tropica to various extents and had significant anti-leishmanial activities, even if some orders were higher than the reference drug Amphotericin B. On the other hand, compounds 5b, 5c, and 5g were found to be ineffective. Additionally, the results of in silico studies have presented the existence of some interactions between the compounds and the active site of sterol 14-alpha-demethylase, a biosynthetic enzyme that plays a critical role in the growth of the parasite. Therefore, it can be suggested that if the results obtained from this study are confirmed with in vivo findings, it may be possible to obtain some new anti-leishmanial drug candidates. © 2023 by the authors.
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3 (4 (1H benzimidazol 2 yl)phenyl) 5 (2 (3,4 dihydoxyphenyl) 4 methyl 2oxo ethylthio) 4H 1,2,4 triazole , 3 (4 (1H benzimidazol 2 yl)phenyl) 5 (2 (3,4 dihydroxyphenyl) 4 ethyl 2 oxo ethylthio) 4H 1,2,4 triazole , 3 (4 (1H benzimidazol 2 yl)phenyl) 5 (2 (4 bromophenyl) 4 ethyl 2 oxo ethylthio) 4H 1,2,4 triazole , 3 (4 (1H benzimidazol 2 yl)phenyl) 5 (2 (4 bromophenyl) 4 methyl 2 oxo ethylthio) 4H 1,2,4 triazole , 3 (4 (1H benzimidazol 2 yl)phenyl) 5 (2 (4 cyanophenyl) 4 ethyl 2 oxo ethylthio) 4H 1,2,4 triazole , 3 (4 (1H benzimidazol 2 yl)phenyl) 5 (2 (4 methylphenyl) 4 ethyl 2 oxo ethylthio) 4H 1,2,4 triazole , 3 (4 (1H benzimidazol 2 yl)phenyl) 5 (2 (4 methylphenyl) 4 methyl 2 oxo ethylthio) 4H 1,2, 4 triazole , 3 (4 (1H benzimidazol 2 yl)phenyl) 5 (2(4 cyanophenyl) 4 methyl 2 oxo ethylthio) 4H 1,2,4 triazole , 3 (4 (1H benzimidazol 2 yl)phenyl) 5 mercapto 2 (4 (4 methyl/ethyl) 4H 1,2,4 triazole , amphotericin B , benzimidazole , benzimidazole derivative , methyl 4 (1H benz[d]imidazol 2 yl) benzoate , methyl 4 (1H benz[d]imidazol 2 yl) benzohydrazide , N methyl ethyl 2 [4 (1H-benzimidazol 2 yl)benzoyl]hydrazine 1 carbothioamide , sterol 14alpha demethylase , triazole , triazole derivative , unclassified drug , amino acid sequence , antileishmanial activity , Article , carbon nuclear magnetic resonance , chemical reaction , controlled study , enzyme active site , Fourier transform infrared spectroscopy , hydrogen bond , IC50 , in vitro study , Leishmania tropica , liquid chromatography-mass spectrometry , molecular docking , molecular dynamics , nonhuman , parasite isolation , parasite viability , physical chemistry , proton nuclear magnetic resonance , XTT assay