Conclusions

Antimicrobial resistance is one of the biggest challenges facing modern healthcare systems. β-lactamases, specifically NDM-1, significantly compromise the clinical efficacy of β-lactam antibiotics. To date, there are no clinically available NDM-1 inhibitors. Captopril has emerged as a validated lead scaffold to design novel derivatives, in particular, the activity is frequently retained in derivatives bearing the mercaptopropionamide motif, highlighting the essential role of the thiol-zinc binding group. Structural optimization strategies, including modification of ring geometry, enhancement of hydrophobic interactions, and fluorination, have demonstrated promising in vitro inhibitory activity. However, translation into clinically viable agents remains limited. The continued development of captopril-inspired derivatives will require better assay standardization alongside integrated structural optimization and biological validation to facilitate their advancement as effective NDM-1 inhibitors.