Abstract

In this study, a total of 17 piece 2,5-disubstituted benzoxazole derivatives were synthesized, 2 of which were not original, their antimicrobial activities were determined using microdilution method and their in vitro cytotoxic activities were investigated on MCF-7 and A549 cells by MTT test. When the activity results are examined, although the antibacterial effects of benzoxazole derivatives are weaker than standard drugs; 3N13 and 3N19 against Candida albicans isolate showed the closest activity to fluconazole with MIC: 16 µg/ml. The cytotoxicity test was measured at a concentration of 100 µM and a 24-h incubation period. The results showed that the compounds had weak activities against two cell lines. Molecular docking studies of synthesized compounds were performed on sterol 14α-demethylase protein (CYP51) and protein-ligand interactions of 3N13, the most effective derivative against C. albicans isolate, were showed (PDB: 5TZ1). Estimated ADME profiles of compounds were calculated and also 3N13’s were calculated HUMO-LUMO energies, molecular electrostatic potential analysis, and geometric optimization parameters with 6-311 G+ (d,p) base set using DFT/B3LYP theory, and the results were displayed.

摘要

本研究共合成了17个2,5-二取代苯并恶唑衍生物，其中2个非原创，采用微量稀释法测定其抗菌活性，并采用微量稀释法测定其对MCF-7和A549细胞的体外细胞毒活性。 MTT 测试。考察活性结果时，虽然苯并恶唑衍生物的抗菌作用弱于标准药物；3N13和3N19针对白色念珠菌分离物表现出与氟康唑最接近的活性，MIC：16 µg/ml。在 100 µM 的浓度和 24 小时的潜伏期下测量细胞毒性试验。结果表明，这些化合物对两种细胞系的活性较弱。合成化合物的分子对接研究对甾醇 14α-去甲基化酶蛋白 (CYP51) 进行了研究，并显示了3N13的蛋白质-配体相互作用，这是对白色念珠菌分离物最有效的衍生物(PDB: 5TZ1)。使用 DFT/B3LYP 理论计算了化合物的估计 ADME 曲线，还计算了3N13的 HUMO-LUMO 能量、分子静电势分析和几何优化参数，其中 6-311 G+ (d,p) 碱基组，结果为显示。