Callistus I Iheme, Asika Kenneth E, Ugwor Emmanuel I, Ogbonna Chukwuka U, Uzoka Ugonna H, Nwabueze Obinna S, Ezirim Amanda U, Nkwoada Amarachi U, Oguzie Chima K, Okoli Uzoamaka A, Mejeha Obioma K, Ekuma Uchechukwu O, Doris I Ukairo, Chiegboka Nneamaka A, Alisi Chinwe S, Ogbulie Judeanthony N
Department of Forensic Science, Federal University of Technology Owerri (FUTO), Nigeria; Department of Biochemistry, FUTO, Nigeria.
Department of Biochemistry, FUTO, Nigeria.
Bioorg Chem. 2025 Aug;163:108764. doi: 10.1016/j.bioorg.2025.108764. Epub 2025 Jul 16.
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.
抗菌耐药性（AMR）对全球卫生部门构成重大威胁。用印楝水粗提物合成了氧化锌纳米颗粒（ZnO NPs），并使用气相色谱-质谱联用（GC-MS）测定其植物化学成分。使用先进的光谱仪和显微镜对它们进行了进一步表征。结果显示了一系列ZnO NPs纳米棒，其最大吸收波长为320 nm。GC-MS显示合成的ZnO NPs中存在20种挥发性植物化学物质。在挥发性化合物中，计算机模拟研究表明滨蒿内酯是最具生物活性的化合物。ZnO NPs分别用提取物中富含滨蒿内酯的部分（ZnO NPs-S）和氨苄青霉素（ZnO NPs-amp）进行功能化。随后，评估了这些纳米颗粒的抗氧化剂以及对耐抗菌性大肠杆菌的体外抗菌性能。体外研究评估了在抗菌剂存在下大肠杆菌的菌落计数（cfu）；ZnO NPs-S、ZnONPs-amp、印楝提取物和氨苄青霉素（标准药物）的脱氢酶抑制特性。在500μm/mL的浓度下，ZnO NPs-S和ZnONPs-amp分别抑制了57.89%和89.74%的酶活性。计算机模拟研究表明，ZnO NPs-S的滨蒿内酯成分是大肠杆菌苹果酸脱氢酶和组氨酸醇脱氢酶结合口袋中烟酰胺腺嘌呤二核苷酸（NAD）最具竞争力的配体。抗氧化剂分析表明，ZnO NPs的抗氧化潜力较差。总之，ZnO NPs-S对耐抗菌性大肠杆菌表现出良好的抗菌性能，并且通过与氨苄青霉素结合得到增强。建议进一步进行毒理学和体内评估研究。
