Synthesis and evaluation of new quinazoline-benzimidazole hybrids as potent anti-microbial agents against multidrug resistant Staphylococcus aureus and Mycobacterium tuberculosis

• Published in: European journal of medicinal chemistry 2021-02, Vol.212, p.112996, Article 112996
• Main Authors: Malasala, Satyaveni, Ahmad, Md Naiyaz, Akunuri, Ravikumar, Shukla, Manjulika, Kaul, Grace, Dasgupta, Arunava, Madhavi, Y.V., Chopra, Sidharth, Nanduri, Srinivas
• Format: Article
• Language: English
• Subjects: anti-bacterial agents; Anti-Bacterial Agents - chemical synthesis; Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - pharmacology; Benzimidazole; Benzimidazoles - chemistry; Benzimidazoles - pharmacology; Cytotoxicity; Dose-Response Relationship, Drug; Microbial Sensitivity Tests; Molecular Structure; MRSA; Mycobacterium tuberculosis - drug effects; Quinazoline; Quinazolines - chemistry; Quinazolines - pharmacology; Resistance; Staphylococcus aureus - drug effects; Structure-Activity Relationship; Tuberculosis
• ISSN: 0223-5234; 1768-3254
• DOI: 10.1016/j.ejmech.2020.112996

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 (CC50 = 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. [Display omitted] •New quinazoline-benzimidazole hybrids identified as antimicrobial agents.•Compounds 8b, 8c, 8d, 8g, 8h, 8i and 10a displayed selective and potent inhibitory activity against S. aureus.•Compounds 8a, 8b, 8f, 8g, and 10c exhibited potent inhibitory activity against different strains of M. tuberculosis.•The selected compounds were found to show less cytotoxicity towards Vero cells with favorable selectivity index.•Possess potent inhibitory activity against MDR strains of S. aureus including VRSA.