Development of Thiazolidinones as Fungal Carbonic Anhydrase Inhibitors

Guezel-Akdemir Ö., Carradori S., Grande R., Demir-Yazici K., Angeli A., Supuran C. T., ...More

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, vol.21, no.8, 2020 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 21 Issue: 8
  • Publication Date: 2020
  • Doi Number: 10.3390/ijms21082960
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, CAB Abstracts, EMBASE, MEDLINE, Veterinary Science Database, Directory of Open Access Journals
  • Keywords: 4-thiazolidinones, antifungal activity, molecular modelling studies, carbonic anhydrases, lanosterol 14 alpha-demethylase, CYP51a1, CgNce103, YEAST CANDIDA-GLABRATA, BETA-CLASS ENZYME, CRYPTOCOCCUS-NEOFORMANS, ETA-CLASS, ALPHA, BACTERIAL, ALBICANS, GAMMA, DERIVATIVES, AGENTS
  • Istanbul University Affiliated: Yes


In our efforts to find new and selective thiazolidinone-based anti-Candida agents, we synthesized and tested 26 thiazolidinones against several Candida spp. and Gram-positive and Gram-negative bacteria. The compounds showed selective antifungal activity with potency similar to fluconazole and clotrimazole, while lacking strong antibacterial activity. Molecular docking and molecular dynamics studies were performed on Candida CYP51a1 and carbonic anhydrase (CA) enzymes to further suggest putative targets that could mediate the antifungal effects of these compounds. Finally, the compounds were tested in enzyme inhibition assays to assess their putative mechanism of action and showed promising K-I values in the 0.1-10 mu M range against the Candida glabrata beta-CA enzyme CgNce103.