Synthesis, antibacterial screening and computational studies of quinazoline-4 (3H)-one-triazole conjugates.

• Full structure elucidation of all compounds using 2D-NMR (HMBC, HSQC, COSY) techniques and other spectral evidence. • Antibacterial screening of compounds against both gram-positive and gram-negative strains. • Most active conjugate exhibited superior activity to ampicillin against klebsiella pneumoniae. • Target identification using pharmacophore modelling and docking simulations. A novel series of quinazoline-4 (3H)-one-tagged triazole conjugates were synthesised using the copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) methodology. All synthesized compounds were structurally elucidated with the help of 2D-NMR (HMBC, HSQC, COSY) techniques and other spectral evidence. The in vitro antibacterial activities of these compounds were evaluated and compared with commercial drugs ciprofloxacin, ampicillin, and levofloxacin. Four compounds (4a, 4d , 4g , and 4i) of the series exhibited potent activity and selectivity against the gram-negative bacterial strains. Amongst these, 4i emerged as the most active conjugate with almost 12-fold superior activity to ampicillin against Klebsiella pneumoniae (gram-negative), one of the most challenging multidrug-resistant strains worldwide. Structure-activity relationship (SAR) analysis further revealed that the incorporation of a triazole ring incredibly increased the antibacterial activity of quinazoline Schiff bases towards the gram-negative bacteria. Moreover, the para -positioning of strong electron-donating (–OCH 3) and electron-withdrawing (-NO 2) groups at the phenyl ring of the triazole ring positively influenced the antibacterial activity, whereas the meta -substitution generally decreased the antibacterial activity of the conjugates. Furthermore, molecular docking studies were conducted to explore the binding characteristics of these compounds in the binding site of DNA gyrase (Staphylocouccus aureus). [ABSTRACT FROM AUTHOR]