Mechanistic insight and in-vitro validation of ampicillin/scoparone-functionalized ZnO nanoparticles as antioxidant, and antimicrobial therapeutics against antimicrobial-resistant Escherichia coli.

Antimicrobial resistance (AMR) poses a significant threat to the global health sector. Zinc oxide nanoparticles (ZnO NPs) were synthesized with aqueous crude extract of Azadirachta indica, and the phytochemical compositions determined using Gas chromatography coupled to mass spectroscopy (GC-MS). They were further characterized using advanced spectroscopes and microscopes. The results showed arrays of ZnO NPs nanorods with maximal absorption wavelengths of 320 nm. The GC-MS revealed the presence of twenty volatile phytochemicals associated with the synthesized ZnO NPs. Among the volatile compounds, in silico study revealed Scoparone as the most bioactive compound. The ZnO NPs were separately functionalized with Scoparone-rich portion of the extract (ZnO NPs-S), and Ampicillin (ZnO NPs-amp). Subsequently, the nanoparticles were assessed for their antioxidants, and in vitro antimicrobial properties on antimicrobial-resistant Escherichia coli. In vitro study assessed the colony counts (cfu) of the E. coli in the presence of the antimicrobials; dehydrogenase inhibitory properties of ZnO NPs-S, ZnONPs-amp, extract of A. indica, and Ampicillin (standard drug). At the concentration of 500 μm/mL, 57.89 % and 89.74 % of the enzyme activities were inhibited by ZnO NPs-S, and ZnONPs-amp respectively. In silico study revealed Scoparone component of ZnO NPs-S as the most viable competitor of nicotinamide adenine dinucleotide (NAD) for E. coli malate and histidinol dehydrogenases binding pockets. Antioxidant analysis revealed that ZnO NPs exhibited poor antioxidant potential. Conclusively, ZnO NPs-S exhibited good antimicrobial properties against antimicrobial-resistant E. coli, and was enhanced through conjugation with Ampicillin. For further studies, toxicological and in vivo assessment are recommended.