In this work, iodinated furopyrazines are examined as new antibacterial agents that target penicillin-binding proteins (PBPs) in Bacillus subtilis and Escherichia coli. With negligible haemolysis and low minimum inhibitory concentrations, the compounds exhibit satisfactory antibacterial action. Stable binding to PBPs is confirmed by molecular docking and dynamics simulations, confirming their promise as potent antibacterial scaffolds for additional drug development.

Abstract

Given the growing burden of multidrug-resistant (MDR) pathogens, particularly Escherichia coli resistance to almost all antibiotics included in the Indian Priority Pathogen List (IPPL), which has been categorized as critical, it is necessary to strengthen the discovery of structurally unique and biologically potent agents. Within this framework, furopyrazines provide an attractive scaffold for constructing antibacterial agents due to their bicarbocyclic structure, which enables favorable pharmacodynamic interactions with vital bacterial targets. The favorable balance between excellent antibacterial efficacy and satisfactory biocompatibility of our lead compound, 6 h, was displayed by MIC and hemolysis tests. The in-silico docking studies revealed the possible mechanism of action in which compound 6 h indicated excellent binding affinity against the bacterial PBP (penicillin-binding protein), such as 7BN9 and 6G9S. The interaction comprised of important interacting residues (AGR A46, ASP A38, and TRP A370) demonstrated its bactericidal potential against bacterial cell wall biosynthesis. Further studies will involve pharmacokinetic profiling, wider testing against MDR clinical isolates according to antimicrobial spectrum and exploring structure–activity relationship (SAR) towards enhancing efficacy while minimizing cytotoxicity. In general, these findings add to progress made in the worldwide battle to create new antibiotics with activity that can bypass existing resistance profiles.