Treatment of nosocomial and community acquired Staphylococcus aureus infections has become more challenging due to the egression of multi-drug resistance. This has spurred the need for rapid development of new therapeutic agents which can effectively negate the resistance mechanisms. In our current work, several new 4-oxoquinazolin-3(4H)-yl)benzoic acid and benzamide derivatives were synthesized and examined for their antimicrobial activity against ESKAP pathogen panel and pathogenic mycobacteria. In the primary screening, compounds 4a, 4b, 6′a, 6′b, 6′h, 6′i and 6′j were found to demonstrate selective and potent inhibitory activity against Staphylococcus aureus (MICs = 0.25–0.5 µg/mL). When tested against Vero cells, all the compounds were found to be non toxic possessing favourable selectivity index (SI > 10), which encouraged us for carrying out further studies. Compound 6′a (SI > 40) was tested against a number of multiple clinical strains of multi-drug resistant S. aureus and was found to exhibit potent activity, irrespective of the resistant status of the strain. Besides, compound 6′a also exhibited concentration dependent bactericidal activity and synergized with the FDA approved drugs tested. The interesting results obtained suggest the potential utility of the newly synthesized compounds for treatment of multidrug resistant S. aureus infections.

由于多种药物耐药性的出现，医院和社区获得性金黄色葡萄球菌感染的治疗变得更具挑战性。这刺激了对快速开发可有效消除耐药机制的新治疗剂的需求。在我们目前的工作中，合成了几种新的4-氧代喹唑啉-3（4 H）-基）苯甲酸和苯甲酰胺衍生物，并检查了它们对ESKAP病原体组和病原性分枝杆菌的抗菌活性。在初步筛选中，化合物4a，4b，6'a，6'b，6'h，6'i和6'j被发现对金黄色葡萄球菌具有选择性和有效的抑制活性（MIC = 0.25–0.5  µg / mL）。当针对Vero细胞进行测试时，发现所有化合物都是无毒的，具有良好的选择性指数（SI> 10），这鼓励我们开展进一步的研究。针对多种具有多重耐药性的金黄色葡萄球菌的多种临床菌株测试了化合物6'a（SI> 40），发现该化合物表现出有效的活性，而与菌株的耐药状态无关。此外，化合物6'a还表现出浓度依赖性的杀菌活性，并与FDA批准的测试药物协同作用。获得的有趣结果表明，新合成的化合物可用于治疗多药耐药的金黄色葡萄球菌感染。