Çavuşoğlu Betül Kaya, Yurttaş Leyla, Cantürk Zerrin
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, Eskisehir, Turkey.
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, Eskisehir, Turkey.
Eur J Med Chem. 2018 Jan 20;144:255-261. doi: 10.1016/j.ejmech.2017.12.020. Epub 2017 Dec 7.
In search of potent and safe antifungal agents, herein, we report the synthesis, characterization and biological activities of triazole-oxadiazole compounds. The structural verification of the molecules was carried out by H NMR, C NMR and mass spectral data. The in vitro antifungal and apoptotic activity were investigated against C. albicans, C. parapsilosis, C. krusei and C. glabrata. The compounds namely N-(4-nitrophenyl)-2-[(5-(2-((4-methyl-4H-1,2,4-triazol-3-yl)thio)ethyl)-1,3,4-oxadiazol-2-yl)thio]acetamide (4e) and N-(6-fluorobenzothiazol-2-yl)-2-[(5-(2-((4-methyl-4H-1,2,4-triazol-3-yl)thio)ethyl)-1,3,4-oxadiazol-2-yl)thio]acetamide (4i) were detected as the most potent compounds against C. albicans and C. glabrata (MIC = 62.5 μg/mL). According to studies on their mechanism of action, it was confirmed that compound 4i has apoptotic effect on four Candida via Annexin V-PI with flow cytometry. The MTT assay revealed that all compounds were determined to be non-toxic against healthy cells in the tested concentrations.
为寻找高效且安全的抗真菌剂，在此，我们报告三唑-恶二唑化合物的合成、表征及生物活性。通过氢核磁共振（H NMR）、碳核磁共振（C NMR）和质谱数据对分子进行结构验证。研究了这些化合物对白色念珠菌、近平滑念珠菌、克柔念珠菌和光滑念珠菌的体外抗真菌及凋亡活性。化合物N-(4-硝基苯基)-2-[(5-(2-((4-甲基-4H-1,2,4-三唑-3-基)硫代)乙基)-1,3,4-恶二唑-2-基)硫代]乙酰胺（4e）和N-(6-氟苯并噻唑-2-基)-2-[(5-(2-((4-甲基-4H-1,2,4-三唑-3-基)硫代)乙基)-1,3,4-恶二唑-2-基)硫代]乙酰胺（4i）被检测为对白色念珠菌和光滑念珠菌最有效的化合物（最低抑菌浓度（MIC）=62.5μg/mL）。根据对其作用机制的研究，通过流式细胞术用膜联蛋白V-碘化丙啶（Annexin V-PI）证实化合物4i对四种念珠菌具有凋亡作用。MTT法显示所有化合物在测试浓度下对健康细胞均无毒性。
