Emerging Chemical Strategies to Combat Antibiotic-Resistant Bacteria: A Multidisciplinary Systematic Review

Abstract

The rapid emergence of antibiotic-resistant bacteria poses a major threat to global healthcare, reducing the effectiveness of conventional antimicrobial therapies and demanding urgent innovation in drug discovery. This systematic review evaluates emerging strategies developed between 2020 and 2026 to combat antimicrobial resistance (AMR), focusing on synthetic medicinal chemistry, nanotechnology, natural products, and artificial intelligence (AI)-assisted drug design. Following PRISMA guidelines, 38 high-impact studies from Scopus, PubMed, Web of Science, and ScienceDirect were analyzed. The findings indicate that β-lactam adjuvants, quinoline-chalcone hybrids, sulfonamide derivatives, silver nanoparticles, and liposomal formulations exhibit strong activity against multidrug-resistant ESKAPE pathogens. Natural alkaloids and flavonoids also demonstrated antimicrobial potential through membrane disruption and efflux pump inhibition, while AI-based molecular docking accelerated lead compound identification. Overall, integrated chemistry-driven and computational approaches offer promising solutions for developing sustainable next-generation antimicrobial therapies against AMR.

Keywords: Antimicrobial resistance; medicinal chemistry; heterocyclic compounds; nanoparticles; natural products; QSAR; drug discovery