How Structure–Function Relationships of 1,4‐Naphthoquinones Combat Antimicrobial Resistance in Multidrug‐Resistant (MDR) Pathogens

Abstract Antimicrobial resistance (AMR) is one of the top ten health‐related threats worldwide. Among several antimicrobial agents, naphthoquinones (NQs) of plant/chemical origin possess enormous structural and functional diversity and are effective against multidrug‐resistant (MDR) pathogens. 1,4‐NQs possess alkyl, hydroxyl, halide, and metal groups as side chains on their double‐ring structure, predominantly at the C‐2, C‐3, C‐5, and C‐8 positions. Among 1,4‐NQs, hydroxyl groups at either C‐2 or C‐5 exhibit significant antibacterial activity against Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter spp. (ESKAPE) and MDR categories. 1,4‐NQs exhibit antibacterial activities like plasmids curing, reactive oxygen species generation, efflux pumps inhibition, anti‐DNA gyrase activity, membrane permeabilization, and biofilm inhibition. This review emphasizes the structure‐function relationships of 1,4‐NQs against ESKAPE and MDR pathogens based on a literature review of studies published in the last 15 years. Overall, 1,4‐NQs have great potential for counteracting the antimicrobial resistance of MDR pathogens.