Synthesis, antimicrobial activity, and molecular docking study of 1,3-oxazines derivatives

Computational methods have become integral in various stages of drug development, from initial hit discovery through lead optimization and beyond. Among these methods, molecular docking stands out as the most extensively employed technique in computer-aided drug design. In this study, the biological activity and molecular docking of the synthesized derivatives were investigated for the first time. An effective one-pot four- component method was studied for the synthesis of (5-hydroxy-2,4-dipheny-2H-benzo[e][1,3]oxazin-3(4H)- yl)(phenyl)methanone derivatives by condensation reaction of Resorcinol with various aromatic aldehydes, carboxylic acids and ammonia. The synthesized compounds underwent testing for their antimicrobial effectiveness against both Gram-positive and Gram-negative bacteria, and were benchmarked against standard drugs like ciprofloxacin. Results indicated that the synthesized compounds exhibited moderate to potent antibacterial properties, a finding further supported by molecular modeling conducted in this study, also, this series of synthesized derivatives of 1,3-oxazines have a significant effect on Gram-negative bacteria compared to Gram-positive bacteria. The computational findings suggested that inhibiting DNA gyrase could achieve antibacterial activity. DNA gyrase in bacteria is a well-established and validated target for developing new antibacterial compounds. Pharmacophore analysis revealed that features such as hydrogen bond acceptors, hydrogen bond donors, and hydrophobicity contribute to this inhibition. However, these computer simulations represent just the beginning stages for initiating new projects aimed at developing antimicrobial molecules.