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Journal of Chemistry
Volume 2017, Article ID 9387102, 15 pages
https://doi.org/10.1155/2017/9387102
Research Article

Synthesis, Molecular Docking Studies, and Antifungal Activity Evaluation of New Benzimidazole-Triazoles as Potential Lanosterol 14α-Demethylase Inhibitors

1Department of Analytical Chemistry, Faculty of Pharmacy, Anadolu University, 26470 Eskişehir, Turkey
2Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, 26470 Eskişehir, Turkey
3Doping and Narcotic Compounds Analysis Laboratory, Faculty of Pharmacy, Anadolu University, 26470 Eskişehir, Turkey
4Department of Pharmaceutical Toxicology, Faculty of Pharmacy, Anadolu University, 26470 Eskişehir, Turkey
5Department of Environmental Engineering, Faculty of Engineering, Anadolu University, Eskişehir, Turkey

Correspondence should be addressed to Yusuf Özkay; rt.ude.ulodana@yakzoy

Received 8 August 2017; Accepted 9 October 2017; Published 12 December 2017

Academic Editor: Gabriel Navarrete-Vazquez

Copyright © 2017 Nafiz Öncü Can et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Due to anticandidal importance of azole compounds, a new series of benzimidazole-triazole derivatives (5a–5s) were designed and synthesized as ergosterol inhibitors. The chemical structures of the target compounds were characterized by spectroscopic methods. The final compounds were screened for antifungal activity against Candida glabrata (ATCC 90030), Candida krusei (ATCC 6258), Candida parapsilosis (ATCC 22019), and Candida albicans (ATCC 24433). Compounds 5i and 5s exhibited significant inhibitory activity against Candida strains with MIC50 values ranging from 0.78 to 1.56 μg/mL. Cytotoxicity results revealed that IC50 values of compounds 5i and 5s against NIH/3T3 are significantly higher than their MIC50 values. Effect of the compounds 5i and 5s against ergosterol biosynthesis was determined by LC-MS-MS analysis. Both compounds caused a significant decrease in the ergosterol level. The molecular docking studies were performed to investigate the interaction modes between the compounds and active site of lanosterol 14-α-demethylase (CYP51), which is as a target enzyme for anticandidal azoles. Theoretical ADME predictions were also calculated for final compounds.