Antibiotic resistance evolves naturally through random mutation. Resistance to antimicrobials is an urgent public health crisis that requires coordinated global action. Among the bacteria, ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) bacteria are a significant cause of multidrug-resistant infections. The challenge is that no alternative molecular platform has been identified to discover abundant antimicrobial hit compounds. In 21st century antimicrobial resistance (AMR) is one of the biggest risks to people health, which is caused by mutations in bacteria that reduce the efficacy of antibiotics used to treat diseases. If AMR continue to develop unchecked, according to a UK government-commissioned, by the year 2050, AMR might kill 10 million people annually. Although some disagree with these forecasts, the World health organization (WHO) and numerous other organizations and professionals consider the AMR epidemic to be a critical issue that must be addressed through a worldwide coordinated action plan.
One of the most significant medical advancements of the 19th century was the development of antibiotics, which redefined the field of medicine and drastically improved the lifespan. However, antibiotics in clinical use have a limited lifespan before obliteration due to the ineludibly re- emergence of resistance. A major challenge in combating antimicrobial resistance is the lack of new antibiotics being discovered.

In this work, a mild one-step synthesis of 2-benzylidene-3-oxobutanamide and its analogs was synthesized, which permits the introduction of an α, β-unsaturated ketone moiety. In-vitro screening, nine analogs exhibited mid-to-high antibacterial activity against WHO-priority drug-resistant pathogens. Potent compounds showed low toxicity to cultured human embryonic kidney cells and hemolysis assay. These findings suggest that these small molecules with excellent high diversity have the potential to combat antibacterial resistance.
List of Publication:
1. Sood A and Kesavan, V. (2023). “Synthesis and antibacterial activity of 2-benzylidene-3-oxobutanmide derivatives against resistant pathogens”, RSC Med. Chem., 14, 1817-1826.
https://doi.org/10.1039/D3MD00051F