Istanbul University, Department of Pharmaceutical Chemistry, Faculty of Pharmacy, 34116 Istanbul, Turkey.
Dipartimento di Farmacia, "G. d'Annunzio" University of Chieti-Pescara, Via dei vestini 31, 66100 Chieti, Italy.
Int J Mol Sci. 2020 Apr 22;21(8):2960. doi: 10.3390/ijms21082960.
In our efforts to find new and selective thiazolidinone-based anti- agents, we synthesized and tested 26 thiazolidinones against several 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 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 values in the 0.1-10 µM range against the β-CA enzyme CgNce103.
在寻找新型、选择性噻唑烷酮类抗真菌剂的过程中，我们合成并测试了 26 种噻唑烷酮类化合物，以评估它们对多种 属真菌、革兰氏阳性菌和革兰氏阴性菌的抑制活性。结果表明，这些化合物具有与氟康唑和克霉唑相当的抗真菌活性，而对革兰氏阳性菌和革兰氏阴性菌的抑制活性较弱。我们进一步对 CYP51a1 和碳酸酐酶（CA）进行了分子对接和分子动力学研究，以探讨这些化合物发挥抗真菌作用的潜在靶标。最后，我们通过酶抑制实验评估了这些化合物的作用机制，结果显示它们对 CgNce103 具有良好的抑制作用，其半数抑制浓度（IC50）值在 0.1-10 μM 范围内。
