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Synthesis of novel ciprofloxacin-avibactam conjugates for the development of second-generation non-β-lactam-β-lactamase inhibitors

DIR@IMTECH: CSIR-Institute of Microbial Technology

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Title Synthesis of novel ciprofloxacin-avibactam conjugates for the development of second-generation non-β-lactam-β-lactamase inhibitors
 
Creator Kumar, Rahul
Pathania, Vikas
Kumar, Shashi
Kumar, Mahender
Nandanwar, Hemraj
Maurya, Sushil K
 
Subject QR Microbiology
 
Description To overcome the antibiotic resistance challenge, we synthesized a novel class of conjugates based on ciprofloxacin and avibactam, covalently linked by diverse amino acids. In vitro studies of these conjugates have shown improved antibacterial efficacy of avibactam when used alone against some ESKAPE pathogens, i.e., S. aureus, E. coli, and A. baumannii. Further, ceftazidime was screened in combination with all conjugates and found to be less synergistically effective than avibactam-ceftazidime co-dosing against K. pneumoniae and E. coli bacterial strains. Subsequently, the top-ranked active conjugates were investigated against the commercially available β-lactamase-II (Penicillinase from Bacillus cereus) through in vitro studies. These studies elucidated two conjugates i.e, 9 (IC50 = 1.69±0.35 nM) and 24b (IC50 = 57.37±5.39 nM), which have higher inhibition profile than avibactam (IC50 = 141.08±12.20 nM). These outcomes allude to avibactam integration with ciprofloxacin is a novel and fruitful approach to discovering clinically valuable next-generation non-β-lactam-β-lactamase inhibitors.
 
Publisher Elsevier Science
 
Date 2023-05-15
 
Type Article
PeerReviewed
 
Relation https://https://www.sciencedirect.com/science/article/pii/S0960894X23001865?via%3Dihub
http://crdd.osdd.net/open/3090/
 
Identifier Kumar, Rahul and Pathania, Vikas and Kumar, Shashi and Kumar, Mahender and Nandanwar, Hemraj and Maurya, Sushil K (2023) Synthesis of novel ciprofloxacin-avibactam conjugates for the development of second-generation non-β-lactam-β-lactamase inhibitors. Bioorganic & Medicinal Chemistry Letters , 88.