Benzofuran-Isoxazole Hybrids: Synthesis, Antimicrobial Activity and Dual Target Docking Studies

Abstract

In this study, five novel heterocyclic molecular hybrids (4a-e) were synthesized by combining benzofuran and isoxazole motifs. Thesecompounds were synthesized via a multistep process starting with 5-chlorosalicylaldehyde. The structures of the synthesized compounds were characterized by IR, 1H NMR and mass spectrometry. Computational tools were employed to predict properties, including antitubercular and antibacterial traits, drug-likeness, bioactivity scores, toxicity and potential molecular targets. In addition to these predictions, in vitro bioactivities were assessed and conducted Schrödinger docking simulations to determine binding affinities to Mycobacterium tuberculosis enoyl-ACP reductase and Escherichia coli topoisomerase IV. Antitubercular efficacy was determined via the MABA method, while antibacterial effectiveness was tested against both Gram-positive and Gram-negative bacteria. The obtained results highlighted the promise of these benzofuranyl-isoxazole hybrids, making them strong contenders for further lead optimization, with the goal of developing more potent and safer pharmaceutical agents.