Dual-acting β-Aminothiochromones: Design, synthesis, and evaluation as antimicrobial and anti-angiogenic agents

Abstract

The quest for novel antimicrobials is critical due to emerging resistance by new microorganism strains. In these circumstances, we designed and synthesized a series of β-aminothiochromones by employing an aziridines ring-opening strategy to discover antimicrobial agents that are effective against multidrug-resistant (MDR) bacteria. Structures of the compounds [3(a-m) and 3a(a-o)] were well characterized and confirmed by the spectroscopic, analytical and single crystal X-ray analysis. Further, we conducted the in vitro antimicrobial assessment studies against selected Gram-positive, and Gram-negative bacterial strains and two fungal strains. In preliminary screening, all synthesized compounds exhibited moderate activity compared to tested standard drugs Ampicillin, Ciprofloxacin and Fluconazole wherein, 3 m and 3ae displayed higher anti-microbial activities. In addition, these analogues exhibited anti-angiogenic properties on HepG2 cells. The in-silico studies on promising hits, 3 m and 3ae on proteins DNA gyrase and Topoisomerase IV indicate that these hybrids possess better binding energy in comparison with standard drugs. Thus, based on in vitro and silico studies, the newly synthesized compounds appear to be potential scaffolds for antimicrobial and anti-angiogenic drug discovery initiatives.

Keywords: ADME prediction; Aminothiochromones; Anti-Angiogenic; Antimicrobial; Molecular docking study.