Abstract
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•A new approach using computational prediction of binding sites & modelling studies, spirobenzimidazo analogues were developed.•Green synthesis of spirobenzimidazo-quinazolines was achieved using Sulphamic Acid as an efficient catalyst.•Evaluation of the pharmacokinetic profile of the titled compounds using basic quantum chemical descriptors.•Anti-bacterial activity, Minimum Inhibitory Concentration, Biofilm inhibition activity have been evaluated.•Statistically significant 3D-QSAR models were generated to recognize crucial protein-ligand interactions.
DNA gyrase and Topoisomerase IV are promising antibacterial drug targets as they regulate bacterial DNA replication and topology. In a quest for novel DNA topoisomerase inhibitors, a multidisciplinary approach was adopted that involves computational prediction of binding sites and molecular modelling followed by green synthesis and biological evaluation of antibacterial activity of spirobenzimidazo quinazolines derivatives. Using basic quantum chemistry principles, we evaluated spirobenzimidazo quinazolines derivatives with their pharmacokinetic profiles. Based on the results of the aforesaid in-silico studies, we synthesized a series of titled compounds using green synthetic methodology that were validated as potential antimicrobial agents. Quantum chemoinformatics based predicted activity for the synthesized compounds 9b, 9c, and 9j was concomitant with biological evaluation of broadspectrum antibacterial activity. Biological evaluation revealed that inhibition of biofilm formation was due to their potential antibacterial activity. We believe that the novel spirobenzimidazo quinazolines have the potential to be alternatives to aminocoumarins and classical quinazolines upon detailed target specific biological studies.