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.

Synergistic and Additive Effects of Menadione in Combination with Antibiotics on Multidrug‐Resistant Staphylococcus aureus: Insights from Structure‐Function Analysis of Naphthoquinones

“…Naphthoquinones possess functional groups predominantly at positions C‐2, C‐3, C‐5, and C‐8 [40] . Addition or removal of specific groups to/from these positions can lead to structural variations.…”

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Staphylococcus aureus biofilm: Formulation, regulatory, and emerging natural products-derived therapeutics

“…Among various antimicrobial agents, naphthoquinones and their derivatives have received great attention due to their exceptional structural diversity and varied biological properties [ 127 ]. 1,4-Naphthoquinone (1,4-NQ) at a concentration of 10 μg/mL was found to inhibit the S. aureus biofilm formation by 55 %, where the microbial motility was reduced.…”

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