Abstract

In the current era, an ever-emerging threat of multidrug-resistant (MDR) pathogens pose serious health challenges to mankind. Researchers are uninterruptedly putting their efforts to design and develop alternative, innovative strategies to tackle the antibiotic resistance displayed by varied pathogens. Among several naturally derived and chemically synthesized compounds, quinones have achieved a distinct position to defeat microbial pathogens. This review unleashes the structural diversity and promising biological activities of naphthoquinones (NQs) and their derivatives documented in the past two decades. Further, realizing their functional potentialities, researchers were encouraged to approach NQs as lead molecules. We have retrieved information that is dedicated on biological applications (antibacterial, antifungal, antiparasitic) of NQs. The multiple roles of NQs offer them a promising armory to combat microbial pathogens including MDR and the ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp.) group. In bacteria, NQs may exhibit their function in the following ways (1) plasmid curing, (2) inhibiting efflux pumps (EPs), (3) generating reactive oxygen species (ROS), (4) the inhibition of topoisomerase activity. Sparse but meticulous literature suggests the mechanistic roles of NQs. We have highlighted the possible mechanisms of NQs and how the targeted drug synthesis can be achieved via molecular docking analysis. This bioinformatics-oriented approach will explicitly lead to the development of effective and most potent drugs against targeted pathogens. The mechanistic approaches of emerging molecules like NQs might prove a milestone to defeat the battle against microbial pathogens.

Highlights

  • Antibiotics represent world-class, assured molecules that have captured a gigantic share in the global market to combat ever-rising and prevalent infections

  • This study revealed the minimum inhibitory concentration (MIC) of shikonin to be 7.8 to 31.2 μg/mL

  • This study revealed that the introduction of a substituted amide group, acid chlorides, in one of the compounds shows superior antibacterial properties as compared with its parent compound

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Summary

Introduction

Antibiotics represent world-class, assured molecules that have captured a gigantic share in the global market to combat ever-rising and prevalent infections. Hydrogen, hydroxyl,and methyl, nitrogen, biological activities ofand quinones are primarily on the position chemical have been reported for aattached broad range ofdependent applications in potential pharmacology [19]. 3rd position with different chemical group derivatives isolated from plant sources including lawsone, juglone, plumbagin, shikonin literature is evident on. This research group assessed the resistance-modulating potential of antibiotics using plumbagin at its subinhibitory concentration of 4 μg/mL This assessment demonstrated a range of MICs for ciprofloxacin (0.25 to 2 μg/mL), amoxicillin (0.25 to 256 μg/mL), ampicillin (0.25 to 256 μg/mL), and ketoconazole (no activity) against test pathogens. Among Gram-negative bacteria, Pseudomonas spp. and E. coli have been frequently tested to determine the antibacterial potency of NQs (Figure 2) Just like those of a natural origin, chemically derivatized 1,4-NQs are widely investigated for antimicrobial potential. Of (A): naturally derived and (B): chemically synthesized 1,4-naphthoquinones

Structure–Activity Relationship and Bioinformatics Approach
Possible Mechanistic Roles of Napthoquinones
Efficiency to Cure Plasmids from Bacteria
Inhibition of Topoisomerase Enzyme
Antifungal Potential of Naphthoquinones
Antiparasitic Potential of Naphthoquinones
Future Prospects
Findings
Conclusions
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