Synthesis, Anticandidal Activity and Molecular Docking Study of Some New Imidazole Derivatives

Abstract

first_page settings Order Article Reprints Font Type: Arial Georgia Verdana Font Size: Aa Aa Aa Line Spacing:    Column Width:    Background: Open AccessAbstract Synthesis, Anticandidal Activity and Molecular Docking Study of Some New Imidazole Derivatives † by Begüm Nurpelin Sağlık 1,2,*, Ayşen Işık 1, Ulviye Acar Çevik 1,2, Yusuf Özkay 1,2 and Serkan Levent 1,2 1 Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, 26470 Eskişehir, Turkey 2 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), 656; https://doi.org/10.3390/proceedings1060656 Published: 19 October 2017 (This article belongs to the Proceedings of Proceedings of the 1st Molecules Medicinal Chemistry Symposium, Barcelona, Spain) Download Download PDF Download PDF with Cover Download XML Versions Notes The azole pharmacophore is still regarded as a viable lead structure for the synthesis of more effective antifungal agents [1,2,3]. In this study, new 2-substituted-N-[4-(1H-imidazole-1-yl) phenyl] acetamide (5a–5g, 6a–6n) derivatives were synthesized and the antifungal activities of these compounds were evaluated. The synthesized compounds consisted of two novel series of imidazole derivatives containing dithiocarbamate (5a–5g) and (benz) azolethiol (6a–6n) side chains that are structurally related to the famous antifungal azole pharmacophore. Their structures were characterized by spectral (IR, 1H NMR, 13C NMR, and MS spectra) analyses. The synthesized compounds were screened for in vitro antifungal activity against pathogenic strains of fungi. Theoretical ADME predictions were calculated for final compounds. A molecular docking study of the most active compound with target ‘lanosterol 14α-demethylase’ (CYP51) [4] was performed to unravel the mode of antifungal action.Compound 5e, which features imidazole and 4-methoxybenzyl piperazine scaffolds, showed the most promising antifungal activity with a MIC50 value of 0.78 ug/mL against Candida krusei. The effect of the compound 5e against ergosterol biosynthesis was observed by the LC-MS-MS method, which is based on quantification of the ergosterol level in C. krusei. Significant interactions were also observed between compound 5e and 14-α-sterol demethylase. In addition to good antifungal activity, all compounds in the series exhibited a good predicted pharmacokinetics profile. AcknowledgmentsThis study was financially supported by Anadolu University Scientific Projects Fund, Project No.: 1705S312.Author ContributionsY.Ö. conceived and designed the experiments; A.I. and U.A.C. performed the synthesis; S.L. performed analysis studies; B.N.S. performed activity tests; B.N.S. performed docking studies; B.N.S., A.I., U.A.C., Y.Ö. and S.L. wrote the paper.Conflicts of InterestThe authors declare no conflict of interest.ReferencesWhite, T.C.; Marr, K.A.; Bowden, R.A. Clinical, cellular, and molecular factors that contribute to antifungal drug resistance. Clin. Microbiol. Rev. 1998, 11, 382–402. [Google Scholar] [CrossRef] [PubMed]Shah, J.J.; Khedkar, V.; Coutinho, E.C.; Mohanraj, K. Design, synthesis and evaluation of benzotriazole derivatives as novel antifungal agents. Bioorg. Med. Chem. Lett. 2015, 25, 3730–3737. [Google Scholar] [CrossRef] [PubMed]Wani, M.Y.; Ahmad, A.; Shiekh, R.A.; Al-Ghamdi, K.J.; Sobral, A.J. 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Proceedings 2017, 1, 656. https://doi.org/10.3390/proceedings1060656 AMA Style Sağlık BN, Işık A, Çevik UA, Özkay Y, Levent S. Synthesis, Anticandidal Activity and Molecular Docking Study of Some New Imidazole Derivatives. Proceedings. 2017; 1(6):656. https://doi.org/10.3390/proceedings1060656 Chicago/Turabian Style Sağlık, Begüm Nurpelin, Ayşen Işık, Ulviye Acar Çevik, Yusuf Özkay, and Serkan Levent. 2017. "Synthesis, Anticandidal Activity and Molecular Docking Study of Some New Imidazole Derivatives" Proceedings 1, no. 6: 656. https://doi.org/10.3390/proceedings1060656 Find Other Styles Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here. Article Metrics No No Article Access Statistics Multiple requests from the same IP address are counted as one view.