Advancements in the Development of Inhibitors Targeting New Delhi Metallo‑β‑lactamase‑1 (NDM‑1) in Gram‑Negative Bacteria: A Systematic Review to Combat Antimicrobial Resistance

Purpose of the Study This research project investigates the development of inhibitors targeting New Delhi Metallo‑β‑lactamase‑1 (NDM‑1), a key enzyme responsible for conferring resistance to β‑lactam antibiotics in Gram‑negative bacteria. NDM‑1 has become a global public health concern due to its ability to inactivate carbapenems, which are often considered last‑resort antibiotics. Scope and Methodology • Systematic Literature Review: Collecting and analyzing peer‑reviewed studies, patents, and clinical trial data. • Comparative Analysis: Assessing inhibitors by structural class (thiols, hydroxamates, boronic acids, cyclic peptides, etc.), mechanism of action, and efficacy in vitro/in vivo. • SAR/QSAR Integration: Applying structure–activity relationships and quantitative models to interpret substituent effects and guide rational drug design. • Clinical Relevance: Evaluating inhibitors tested against multidrug‑resistant Gram‑negative pathogens such as Klebsiella pneumoniae, Escherichia coli, and Acinetobacter baumannii. Expected Outcomes • Comprehensive Knowledge Base: A consolidated resource summarizing all major advancements in NDM‑1 inhibitor development. • Lead Candidate Identification: Highlighting molecules with strong inhibitory activity and favorable pharmacological profiles. • Strategic Roadmap: Recommendations for future research directions, including hybrid QSAR approaches and synergistic drug combinations.