Abstract

Chalcone is a naturally derived compound which has well-known for its antimicrobial potency. Different factors reduced the efficiency of drug derivatives effective drugs always remain in demand. In this present work, bioisosteric replacement of carboxyl group is described in 1a–h, 2a–h, 3a–h and 4a–h) via microwave-assisted synthesis with excellent yields (46.76–94.59%). The antimicrobial evaluation against S. aureus depicted excellent inhibition of 1b, 1h and 3a–h with higher inhibition zones (11–18 mm) compared to that of ampicillin (11 mm). The structure-activity relationship was supported by molecular docking studies of 1b and 3h on S. aureus 4-pql protein with the binding affinity of −6.7 and −7.8 kcal/mol respectively. The DFT studies depicted the energy gap (ΔE) values 4.12 eV and 4.48 eV for compounds 1b and 3h, respectively. The presence of electron-withdrawing group (EWG) of fluorine substituent on the pyrazoline network has increased the antimicrobial activity as compared to chalcone derivatives. This study is profitable to medicinal industries in designing new drugs that benefit mankind.

摘要

查尔酮是一种天然衍生的化合物，以其抗菌效力而闻名。不同因素降低了药物衍生物的效率，有效药物始终保持需求旺盛。在目前的工作中，通过微波辅助合成在1a-h、2a-h、3a-h和4a-h中描述了羧基的生物等排置换，产率高达 46.76-94.59%。针对金黄色葡萄球菌的抗菌评估表明，与氨苄青霉素（11 mm）相比，1b、1h和3a-h具有更高的抑菌圈（11-18 mm），具有出色的抑制作用。结构 - 活性关系得到分子对接研究的支持在金黄色葡萄球菌4-pql蛋白上的1b和3h，结合亲和力分别为-6.7和-7.8 kcal/mol。DFT 研究描述了化合物1b和3h的能隙 (ΔE) 值分别为 4.12 eV 和 4.48 eV 。与查尔酮衍生物相比，吡唑啉网络上氟取代基的吸电子基团 (EWG) 的存在提高了抗菌活性。这项研究有助于医药行业设计造福人类的新药。