Abstract

We previously synthesized a series of quinoline-2-carbaldehyde hydrazone derivatives and evaluated their antioxidant activities. In this study, the antimicrobial activities of these quinoline-2-carbaldehyde hydrazone derivatives were evaluated antimicrobial activity by the microdilution method, and there cytotoxic effect was investigated in MCF-7 and A549 cells by MTT assay. When the activity results were examined, although the antimicrobial activity of quinoline derivatives were equal or better than standard drugs in general, compound 4 (2 µg/mL) and 8 (1 µg/mL) against E. faecalis and 5 (8 µg/mL) against P. aeruginosa are the most effective derivatives of the series. Besides, disk diffusion test was applied to these three compounds, and significant zone formation was observed at 8 (7 mm) compared to vancomycin (9 mm). Compounds showed no antiproliferative in A549 and MCF-7 cell lines, and compound 4, 5, and 8, which showed the most effective antimicrobial activity, were examined in healthy cells (Beas-2b) and no effect on cell viability was found. To understand the mechanism of this action of these compounds against E. faecalis, molecular docking studies were performed on 15 different proteins, and it was concluded that the compounds interacted with FabH and not enough with other protein structures. The theoretical ADME profiles of compounds comply with Lipinski and other limiting rules. Also, some theoretical quantum parameters (HOMO-LUMO) of compounds, and both MEP analysis and geometric optimization analysis of 8 were calculated with 6–311 G (d,p) base set and DFT/B3LYP theory, and the results were shown.

摘要

我们之前合成了一系列 quinoline-2-carbaldehyde hydrazone 衍生物并评估了它们的抗氧化活性。本研究采用微量稀释法评价这些喹啉-2-甲醛腙衍生物的抗菌活性，并通过MTT法研究MCF-7和A549细胞的细胞毒作用。检验活性结果时，虽然喹啉衍生物的抗菌活性总体上与标准药物相当或优于标准药物，但化合物4 (2 µg/mL) 和8 (1 µg/mL) 对粪肠球菌和5 (8 µg /mL) mL) 抗铜绿假单胞菌是该系列中最有效的衍生物。此外，对这三种化合物进行了圆盘扩散试验，与万古霉素（9 mm）相比，在8 （7 mm）处观察到明显的区域形成。化合物在 A549 和 MCF-7 细胞系中没有显示出抗增殖作用，在健康细胞 (Beas-2b) 中检测了显示出最有效抗菌活性的化合物4、5和8 ，未发现对细胞活力的影响。了解这些化合物对粪肠球菌的这种作用机制, 对 15 种不同的蛋白质进行了分子对接研究，得出的结论是这些化合物与 FabH 相互作用而与其他蛋白质结构相互作用不足。化合物的理论 ADME 曲线符合 Lipinski 和其他限制规则。此外，利用6-311 G（d，p）基组和DFT / B3LYP理论计算了化合物的一些理论量子参数（HOMO-LUMO），以及8的MEP分析和几何优化分析，并显示了结果。