Regioselective synthesis, structural and bioactivity of acetylated 1,5-benzodiazepin-2-one derivatives — X-ray crystallography, DFT and molecular docking approaches

Abstract

Benzodiazepines, a well-studied class of seven-membered aromatic heterocycles containing two nitrogen atoms, have shown great promise as therapeutic agents. Efficient protocols have been developed to synthesize a variety of functionalized benzodiazepines. This study focuses on the synthesis of three derivatives of 1,5-benzodiazepin-2-one through regioselective acetylation using acetyl chloride under various conditions. One of the derivatives was characterized for its molecular and crystal structure using X-ray crystallography, Hirshfeld surfaces, and density functional theory computations (at wB97X-D/aug-cc-pVTZ level). The synthesized compounds were then subjected to in vitro evaluation to assess their antibacterial and antifungal activities against multiple strains. Additionally, their antioxidant and anti-inflammatory properties were examined. The results showed different levels of inhibitory effects on the growth of microorganisms, with all compounds displaying moderate to significant biological activities. Furthermore, molecular docking simulations were conducted to investigate the binding interactions of the compounds with bacterial and fungal targets. This research enhances our understanding of the chemistry of benzodiazepine derivatives and further highlights their therapeutic potential.