Design, Synthesis Molecular Docking Study and Antifungal Activity Evaluation of New Benzimidazole-Triazole Derivatives †
1
Department of Pharmaceutical Toxicology, Faculty of Pharmacy, Anadolu University, 26470 Eskişehir, Turkey
2
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, 26470 Eskişehir, Turkey
3
Doping and Narcotic Compounds Analysis Laboratory, Faculty of Pharmacy, Anadolu University, 26470 Eskişehir, Turkey
*
Author to whom correspondence should be addressed.
†
Presented at the 1st Molecules Medicinal Chemistry Symposium, Barcelona, Spain, 8 September 2017.
Proceedings 2017, 1(6), 647; https://doi.org/10.3390/proceedings1060647
Published: 19 October 2017
(This article belongs to the Proceedings of Proceedings of the 1st Molecules Medicinal Chemistry Symposium, Barcelona, Spain)
Lanosterol 14α-demethylase (CYP51) is an essential enzyme in the fungal life cycle and also an important target for antifungal drug development. Selective inhibition of the enzyme would cause depletion of ergosterol and accumulation of lanosterol and result in the growth inhibition of the fungal cell [1].
In this study, a series of benzimidazole derivatives containing a triazole ring that are structurally related to the famous antifungal azole pharmacophore were synthesized and their structures were characterized by spectral (IR, 1H-NMR, 13C-NMR, and MS spectra) analyses. Compounds 5i and 5s showed the most promising antifungal activity with a MIC50 value of 0.39 ug/mL against Candida species. Molecular docking studies were performed to investigate the mode of action towards the fungal lanosterol 14α-demethylase. ADME studies were carried out and a connection between activities and physicochemical properties of the target compounds was determined. The effect of the active compounds against ergosterol biosynthesis was observed by the LC-MS-MS method.
Acknowledgments
This study was financially supported by Anadolu University Scientific Projects Fund, Project No: 1705S312.
Author Contributions
Y.O. conceived and designed the experiments; U.A.Ç. performed the synthesis, analysis studies, activity tests and docking studies; B.K. and O.A. performed the toxicity tests; B.K., U.A.Ç., Y.O. and O.A. wrote the paper.
Conflicts of Interest
The authors declare no conflict of interest.
References
- Morrison, A.M.S.; Goldstone, J.V.; Lamb, D.C.; Kubota, A.; Lemaire, B.; Stegeman, J.J. Identification, modeling and ligand affinity of early deuterostome CYP51s, and functional characterization of recombinant zebrafish sterol 14α-demethylase. Biochim. Biophys. Acta 2014, 1840, 1825–1836. [Google Scholar] [CrossRef] [PubMed]
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MDPI and ACS Style
Korkut, B.; Çevik, U.A.; Özkay, Y.; Atlı, Ö. Design, Synthesis Molecular Docking Study and Antifungal Activity Evaluation of New Benzimidazole-Triazole Derivatives. Proceedings 2017, 1, 647. https://doi.org/10.3390/proceedings1060647
AMA Style
Korkut B, Çevik UA, Özkay Y, Atlı Ö. Design, Synthesis Molecular Docking Study and Antifungal Activity Evaluation of New Benzimidazole-Triazole Derivatives. Proceedings. 2017; 1(6):647. https://doi.org/10.3390/proceedings1060647
Chicago/Turabian StyleKorkut, Büşra, Ulviye Acar Çevik, Yusuf Özkay, and Özlem Atlı. 2017. "Design, Synthesis Molecular Docking Study and Antifungal Activity Evaluation of New Benzimidazole-Triazole Derivatives" Proceedings 1, no. 6: 647. https://doi.org/10.3390/proceedings1060647
