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 KI values in the 0.1–10 µM range against the Candida glabrata β-CA enzyme CgNce103.
Development of thiazolidinones as fungal carbonic anhydrase inhibitors / Guzel-Akdemir O.; Carradori S.; Grande R.; Demir-Yazici K.; Angeli A.; Supuran C.T.; Akdemir A.. - In: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES. - ISSN 1661-6596. - ELETTRONICO. - 21:(2020), pp. 2960.2960-2960.2960. [10.3390/ijms21082960]
Development of thiazolidinones as fungal carbonic anhydrase inhibitors
Angeli A.;Supuran C. T.;
2020
Abstract
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 KI values in the 0.1–10 µM range against the Candida glabrata β-CA enzyme CgNce103.I documenti in FLORE sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.