金黄色葡萄球菌
抗菌剂
体内
微生物学
化学
生物膜
耐甲氧西林金黄色葡萄球菌
抗生素
离体
抗菌活性
万古霉素
细菌
组合化学
体外
生物
生物化学
遗传学
生物技术
作者
Kajal Chaudhary,Bhumika Agrahari,Barnali Biswas,Niranjan D. Chatterjee,Ayushi Chaudhary,Awanish Kumar,Himanshu Sonkar,Sumedha Dewan,D. K. Saxena,Abdul Akhir,Nidhi Malhotra,Sidharth Chopra,Santosh K. Misra,Saravanan Matheswaran,Ranvir Singh
标识
DOI:10.1002/adhm.202400378
摘要
Abstract In the pursuit to combat stubborn bacterial infections, particularly those stemming from gram‐positive bacteria, our study is an attempt to craft a precision‐driven platform characterized by unparalleled selectivity, specificity, and synergistic antimicrobial mechanisms. Leveraging remarkable potential of metalloantibiotics in antimicrobial applications, herein, we rationally design, synthesize, and characterize a new library of Pyridine‐2,6‐dicarboxamide ligands and their corresponding transition metal Cu(II)/Zn(II) complexes. The lead compound L 11 demonstrate robust antibacterial properties against Staphylococcus aureus (MIC = 2‐16 µg/mL), methicillin and vancomycin‐resistant S. aureus (MIC = 2‐4 µg/mL) and exhibit superior antibacterial activity when compared to FDA‐approved vancomycin, the drug of last resort. Additionally, the compound exhibited notable antimicrobial efficacy against resistant enterococcus strains (MIC = 2‐8 µg/mL). To unravel mechanistic profile, advanced imaging techniques including SEM and AFM were harnessed, collectively suggesting a mechanistic pathway involving cell wall disruption. Live/dead fluorescence studies further confirm efficacy of L 11 and its complexes against S. aureus membranes. Our translational exploration extends to a rat model, indicating promising In‐vivo therapeutic potential. Thus, our comprehensive research initiative has capabilities to transcends the confines of our laboratory, heralding a pivotal step toward combatting antibiotic‐resistant pathogens and advancing the frontiers of metalloantibiotics based therapy with a profound clinical implication. This article is protected by copyright. All rights reserved
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