title: New Benzimidazole-1,2,4-Triazole Hybrid Compounds: Synthesis, Anticandidal Activity and Cytotoxicity Evaluation.
abstract: Owing to the growing need for antifungal agents, we synthesized a new series 2-((5-(4-(5-substituted-1H-benzimidazol-2-yl)phenyl)-4-substituted-4H-1,2,4-triazol-3-yl)thio)-1-(substitutedphenyl)ethan-1-one derivatives, which were tested againstCandidaspecies. The synthesized compounds were characterized and elucidated by FT-IR, ¹H-NMR,13C-NMR and HR-MS spectroscopies. The synthesized compounds were screened in vitro anticandidal activity againstCandidaspecies by broth microdiluation methods. In vitro cytotoxic effects of the final compounds were determined by MTT assay. Microbiological studies revealed that compounds5m,5o,5r,5t,5y,5ab, and5adpossess a good antifungal profile. Compounds5wwas the most active derivative and showed comparable antifungal activity to those of reference drugs ketoconazole and fluconazole. Cytotoxicity evaluation of compounds5m,5o,5r,5w,5y,5aband5adshowed that compounds5wand5adwere the least cytotoxic agents. Effects of these two compounds against ergosterol biosynthesis were observed by LC-MS-MS method, which is based on quantification of ergosterol level inC. albicans. Compounds5wand5dinhibited ergosterol biosynthesis concentration dependently. A fluorescence microscopy study was performed to visualize effect of compound5wagainstC. albicansat cellular level. It was determined that compound5whas a membrane damaging effect, which may be related with inhibition of biosynthesis of ergosterol.
authors.affiliation: Department of Pharmaceutical Microbiology, Faculty of Pharmacy, Anadolu University, Eskişehir 26470, Turkey. hulyakaraca@anadolu.edu.tr.
authors.forename: Hülya
authors.initials: H
authors.lastname: Karaca Gençer
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, Eskişehir 26470, Turkey. uacar@anadolu.edu.tr.|Doping and Narcotic Compounds Analysis Laboratory, Faculty of Pharmacy, Anadolu University, Eskişehir 26470, Turkey. uacar@anadolu.edu.tr.
authors.forename: Ulviye
authors.initials: U
authors.lastname: Acar Çevik
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, Eskişehir 26470, Turkey. serkanlevent@anadolu.edu.tr.|Doping and Narcotic Compounds Analysis Laboratory, Faculty of Pharmacy, Anadolu University, Eskişehir 26470, Turkey. serkanlevent@anadolu.edu.tr.
authors.forename: Serkan
authors.initials: S
authors.lastname: Levent
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, Eskişehir 26470, Turkey. bnsaglik@anadolu.edu.tr.|Doping and Narcotic Compounds Analysis Laboratory, Faculty of Pharmacy, Anadolu University, Eskişehir 26470, Turkey. bnsaglik@anadolu.edu.tr.
authors.forename: Begüm Nurpelin
authors.initials: BN
authors.lastname: Sağlık
authors.affiliation: Department of Pharmaceutical Toxicology, Faculty of Pharmacy, Anadolu University, Eskişehir 26470, Turkey. busrakorkut@anadolu.edu.tr.
authors.forename: Büşra
authors.initials: B
authors.lastname: Korkut
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, Eskişehir 26470, Turkey. yozkay@anadolu.edu.tr.|Doping and Narcotic Compounds Analysis Laboratory, Faculty of Pharmacy, Anadolu University, Eskişehir 26470, Turkey. yozkay@anadolu.edu.tr.
authors.forename: Yusuf
authors.initials: Y
authors.lastname: Özkay
authors.affiliation: Department of Pharmaceutical Toxicology, Faculty of Pharmacy, Anadolu University, Eskişehir 26470, Turkey. silgin@anadolu.edu.tr.
authors.forename: Sinem
authors.initials: S
authors.lastname: Ilgın
authors.affiliation: Doping and Narcotic Compounds Analysis Laboratory, Faculty of Pharmacy, Anadolu University, Eskişehir 26470, Turkey. yozturk@anadolu.edu.tr.|Department of Pharmacology, Faculty of Pharmacy, Anadolu University, Eskişehir 26470, Turkey. yozturk@anadolu.edu.tr.
authors.forename: Yusuf
authors.initials: Y
authors.lastname: Öztürk
mesh_terms: D000818:Animals; D001562:Benzimidazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002175:Candida / Q000187:drug effects* / Q000378:metabolism; D004875:Ergosterol / Q000378:metabolism; D015394:Molecular Structure; D013329:Structure-Activity Relationship
chemical_list: D001562:Benzimidazoles; D004875:Ergosterol
keywords: 1,2,4-triazole; NIH/3T3; antifungal activity; cytotoxicity; ergosterol