Synthesis, X-ray, Hirshfeld Surface Analysis, Antibacterial Activity, and Computational Investigations of New Benzimidazo[1,2-c]quinazolines and Indolo[2,3-b]quinoxalines

Novel benzimidazo[1,2-c]quinazoline and indolo[2,3-b]quinoxaline derivatives were synthesized and characterized using ¹H and ¹³C NMR, LC-MS, and single-crystal X-ray diffraction techniques. A detailed analysis of the surface properties, intermolecular interactions, crystal packing characteristics, and antibacterial activity is given. The observed results reveal subtle differences in the Hirshfeld surface characteristics of these compounds, indicating variations in crystal packing and molecular recognition properties. The evaluation of antibacterial activity demonstrated that the synthesized compounds have promising broad-spectrum efficacy against both Gram-positive and Gram-negative bacteria. Molecular docking analysis reveals strong binding interactions, emphasizing the potency of benzimidazo[1,2-c]quinazoline and indolo[2,3-b]quinoxaline derivatives to act as an antimicrobial agent. Moreover, quinazoline derivatives' superior absorption and permeability properties suggest enhanced oral bioavailability compared to ampicillin despite considerations of increased lipophilicity and potential drug interactions. These compounds' balanced physicochemical properties and favorable drug-likeness scores indicate their potential as promising drug candidates, particularly for conditions requiring improved tissue penetration. Molecular dynamics simulations support the structural features, highlighting stable binding site occupation and strong off-diagonal interactions, further underscoring its potential in drug design and development.