Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad, 500 037, Telangana, India.
Division of Microbiology, CSIR-Central Drug Research Institute, Sitapur Road, Sector 10, Janakipuram Extension, Lucknow, 226031, Uttar Pradesh, India; AcSIR, Ghaziabad, Sector 19, Kamla Nehru Nagar, Ghaziabad, 201002, Uttar Pradesh, India.
Eur J Med Chem. 2021 Feb 15;212:112996. doi: 10.1016/j.ejmech.2020.112996. Epub 2020 Nov 6.
Owing to the rapid rise in antibiotic resistance, infectious diseases have become serious threat to public health. There is an urgent need to develop new antimicrobial agents with diverse chemical structures and novel mechanisms of action to overcome the resistance. In recent years, Quinazoline-benzimidazole hybrids have emerged as a new class of antimicrobial agents active against S. aureus and M. tuberculosis. In the current study, we designed and synthesized fifteen new Quinazoline-benzimidazole hybrids and evaluated them for their antimicrobial activity against S. aureus ATCC 29213 and M. tuberculosis H37Rv. These studies led to the identification of nine potent antibacterial agents 8a, 8b, 8c, 8d, 8f, 8g, 8h, 8i and 10c with MICs in the range of 4-64 μg/mL. Further, these selected compounds were found to possess potent antibacterial potential against a panel of drug-resistant clinical isolates which include methicillin and vancomycin-resistant S. aureus. The selected compounds were found to be less toxic to Vero cells (CC = 40-≥200 μg/mL) and demonstrated a favourable selectivity index. Based on the encouraging results obtained these new benzimidazol-2-yl quinazoline derivatives have emerged as promising antimicrobial agents for the treatment of MDR- S. aureus and Mycobacterial infections.
由于抗生素耐药性的迅速上升，传染病已成为严重威胁公众健康的因素。因此，迫切需要开发具有不同化学结构和新颖作用机制的新型抗菌药物，以克服耐药性。近年来，喹唑啉-苯并咪唑杂合体已成为一类新的抗菌药物，对金黄色葡萄球菌和结核分枝杆菌具有活性。在本研究中，我们设计并合成了十五种新的喹唑啉-苯并咪唑杂合体，并评估了它们对金黄色葡萄球菌 ATCC 29213 和结核分枝杆菌 H37Rv 的抗菌活性。这些研究确定了 9 种具有潜在抗菌活性的化合物 8a、8b、8c、8d、8f、8g、8h、8i 和 10c，其 MIC 范围为 4-64μg/mL。此外，这些选定的化合物对包括耐甲氧西林和万古霉素的金黄色葡萄球菌在内的一系列耐药临床分离株具有强大的抗菌潜力。这些选定的化合物对 Vero 细胞的毒性较低（CC=40-≥200μg/mL），并具有良好的选择性指数。基于所获得的令人鼓舞的结果，这些新型苯并咪唑-2-基喹唑啉衍生物已成为治疗耐多药金黄色葡萄球菌和分枝杆菌感染的有前途的抗菌药物。
