title: Synthesis and biological evaluation of new naphthalene substituted thiosemicarbazone derivatives as potent antifungal and anticancer agents.
abstract: New thiosemicarbazone derivatives (1-10) were obtained via the reaction of 4-(naphthalen-1-yl)thiosemicarbazide with fluoro-substituted aromatic aldehydes. The synthesized compounds were evaluated for their in vitro antifungal effects against pathogenic yeasts and molds using broth microdilution assay. Ames and umuC assays were carried out to determine the genotoxicity of the most effective antifungal derivatives. Furthermore, all compounds were evaluated for their cytotoxic effects on A549 human lung adenocarcinoma and NIH/3T3 mouse embryonic fibroblast cell lines using XTT test. Among these derivatives, 4-(naphthalen-1-yl)-1-(2,3-difluorobenzylidene)thiosemicarbazide (1) and 4-(naphthalen-1-yl)-1-(2,5-difluorobenzylidene)thiosemicarbazide (3) can be identified as the most promising antifungal derivatives due to their notable inhibitory effects on Candida species and no cytotoxicity against NIH/3T3 mouse embryonic fibroblast cell line. According to Ames and umuC assays, compounds 1 and 3 were classified as non-mutagenic compounds. On the other hand, 4-(naphthalen-1-yl)-1-(2,4-difluorobenzylidene)thiosemicarbazide (2) can be considered as the most promising anticancer agent against A549 cell line owing to its notable inhibitory effect on A549 cells with an IC50 value of 31.25 μg/mL when compared with cisplatin (IC50 = 16.28 μg/mL) and no cytotoxicity against NIH/3T3 cells.
authors.affiliation: Anadolu University, Faculty of Pharmacy, Department of Pharmaceutical Chemistry, 26470 Eskişehir, Turkey.
authors.forename: Mehlika Dilek
authors.initials: MD
authors.lastname: Altıntop
authors.affiliation: Anadolu University, Faculty of Pharmacy, Department of Pharmaceutical Toxicology, 26470 Eskişehir, Turkey.
authors.forename: Özlem
authors.initials: Ö
authors.lastname: Atlı
authors.affiliation: Anadolu University, Faculty of Pharmacy, Department of Pharmaceutical Toxicology, 26470 Eskişehir, Turkey.
authors.forename: Sinem
authors.initials: S
authors.lastname: Ilgın
authors.affiliation: Anadolu University, Faculty of Science, Department of Biology, 26470 Eskişehir, Turkey.
authors.forename: Rasime
authors.initials: R
authors.lastname: Demirel
authors.affiliation: Anadolu University, Faculty of Pharmacy, Department of Pharmaceutical Chemistry, 26470 Eskişehir, Turkey.
authors.forename: Ahmet
authors.initials: A
authors.lastname: Özdemir
authors.affiliation: Anadolu University, Faculty of Pharmacy, Department of Pharmaceutical Chemistry, 26470 Eskişehir, Turkey. Electronic address: zakaplan@anadolu.edu.tr.
authors.forename: Zafer Asım
authors.initials: ZA
authors.lastname: Kaplancıklı
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002175:Candida / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D051379:Mice; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D041681:NIH 3T3 Cells; D009281:Naphthalenes / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013882:Thiosemicarbazones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000935:Antifungal Agents; D000970:Antineoplastic Agents; D009281:Naphthalenes; D013882:Thiosemicarbazones; C031721:naphthalene
keywords: Antifungal activity; Cytotoxicity; Fluorine; Genotoxicity; Naphthalene; Thiosemicarbazone