Synthesis and biological evaluation of new naphthalene substituted thiosemicarbazone derivatives as potent antifungal and anticancer agents

ALTINTOP M. D., ATLI EKLİOĞLU Ö., ILGIN S., DEMİREL R., ÖZDEMİR A., KAPLANCIKLI Z. A.

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, cilt.108, ss.406-414, 2016 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 108
  • Basım Tarihi: 2016
  • Doi Numarası: 10.1016/j.ejmech.2015.11.041
  • Dergi Adı: EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Index Chemicus (IC)
  • Sayfa Sayıları: ss.406-414
  • Anahtar Kelimeler: Thiosemicarbazone, Naphthalene, Fluorine, Antifungal activity, Cytotoxicity, Genotoxicity, SCHIFF-BASES, MEDICINAL CHEMISTRY, IRON CHELATORS, MANNICH-BASES, IN-VITRO, FLUORINE, IDENTIFICATION, ANTIBACTERIAL, CYTOTOXICITY, DISCOVERY
  • Bilecik Şeyh Edebali Üniversitesi Adresli: Hayır

Özet

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 KIT 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 anti fungal 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-yI)-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 mu g/mL when compared with cisplatin (IC50 = 16.28 mu g/mL) and no cytotoxicity against NIH/3T3 cells. (C) 2015 Elsevier Masson SAS. All rights reserved.