Synthetic Optimization and Antibacterial Activity of Novel Benzodioxepine-Biphenyl Amide Derivatives

The biosynthesis of fatty acids is an important metabolic pathway in bacterial organisms. Previous studies have highlighted the synthesis of antimicrobial compounds anchored in the benzodioxepin scaffold and known for their pronounced antibacterial properties. Based on this fundamental knowledge, a series of eight innovative benzodioxepin-biphenyl amide derivatives were carefully designed and synthesized in the current research work. This was achieved through a sophisticated optimization of the synthetic methods. The scope of this study extends to a rigorous evaluation of the antibacterial properties and biocompatibility of the above-mentioned new derivatives. In particular, compound E4 proved to be an extremely effective antimicrobial agent. In addition to a detailed elucidation of the crystalline architecture of compound E4, a thorough docking study was also carried out to investigate the interactions with the enzyme FabH.