Abstract

The increasing resistance to antimicrobial drugs has instigated the crucial need for the discovery of novel compounds with different modes of action that could target both sensitive and resistant strains. For this purpose, we developed some new chalcone analogs. Herein, a novel series of hybrid biphenyl chalcones (17-24), which have organohalogens in their B ring, were synthesized and examined for their antimicrobial effect. The position of the substituent on ring B was changed to find the effect of the substitution on antimicrobial activity. Compounds 18, 19, and 24 showed better antibacterial and antifungal activity when compared other compounds. Also, molecular docking studies on ATP binding site of S. aureus DNA gyrase for antibacterial targets were performed to elucidate the mechanism of antibacterial activity of synthesized compounds. Three of the most active compounds could be considered as lead compounds for the development of more new potent agents.

摘要

对抗菌药物的耐药性日益增加，迫切需要发现具有不同作用模式的新型化合物，这些化合物可以针对敏感菌株和耐药菌株。为此，我们开发了一些新的查尔酮类似物。在此，合成了一系列新的杂合联苯查耳酮 ( 17-24 )，其 B 环中含有有机卤素，并对其抗菌效果进行了检测。改变环 B 上取代基的位置以发现取代对抗菌活性的影响。与其他化合物相比，化合物18、19和24显示出更好的抗菌和抗真菌活性。此外，对 ATP 结合位点的分子对接研究对抗菌靶点的金黄色葡萄球菌DNA 促旋酶进行了研究，以阐明合成化合物的抗菌活性机制。三种最活跃的化合物可被视为开发更有效的新药物的先导化合物。