Novel hybrids-based quinazolinone: Synthesis, characterization, in vitro and in silico antibacterial investigations

Quinazoline-4(3H)-one derivatives constitute a promising class of heterocyclic skeletons with broad pharmacological potential due to their ability to interact with various biological targets such as protein kinases, receptors, and enzymes. In this study, a series of new quinazoline-4(3H)-one-acetamide hybrids was synthesized by N-alkylation reaction, combining these pharmacophores known for their potent bioactivities. The structures of the synthesized compounds were confirmed by infrared spectroscopy (IR), nuclear magnetic resonance (NMR), and high-resolution mass spectrometry (HRMS). The antibacterial activity of the hybrids was evaluated in vitro against five pathogenic bacterial strains: Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Salmonella enterica, and Bacillus subtilis. Several of the synthesized hybrids demonstrated promising antibacterial effects, with compounds 3b, 3h, and 3f exhibiting the most significant activity. In silico studies, including molecular docking simulations, ADMET predictions, and molecular dynamics simulations, corroborated these results by revealing strong binding affinities and favorable pharmacokinetic profiles. Overall, the results suggest that the synthesized quinazolinone-acetamide hybrids, particularly compounds 3b, 3h, and 3f, show potential as effective antibacterial agents.