Probing the benzofuroquinolinium derivative as a potent antibacterial agent through the inhibition of FtsZ activity

• Published in: Journal of pharmacological sciences Vol. 138; no. 1; pp. 83 - 85
• Main Authors: Sun, Ning, Ban, Li, Li, Ming, Fang, Zhiyuan, Li, Xiaomei, Yao, Wenxia, Pan, Jinghui, Lu, Yujing, Liu, Zhihua, Wong, Wing-Leung
• Format: Journal Article
• Language: English
• Published: Japan Elsevier B.V 01.09.2018; Elsevier
• Subjects: Anti-Bacterial Agents - pharmacology; Antibacterial activity; Bacterial Proteins - metabolism; Bacterial resistance; Benzofurans - pharmacology; Cell Division - drug effects; Cytoskeletal Proteins - metabolism; Drug Resistance, Bacterial; FtsZ inhibitor; Glycogen Debranching Enzyme System - metabolism; Gram-Negative Bacteria - cytology; Gram-Negative Bacteria - drug effects; Gram-Negative Bacteria - genetics; Gram-Negative Bacteria - metabolism; Gram-Positive Bacteria - cytology; Gram-Positive Bacteria - drug effects; Gram-Positive Bacteria - genetics; Gram-Positive Bacteria - metabolism; Lactams - pharmacology; Methicillin-Resistant Staphylococcus aureus - drug effects; Polymerization - drug effects; Quinolinium Compounds - pharmacology; Antibacterial activity; Bacterial resistance; FtsZ inhibitor
• ISSN: 1347-8613; 1347-8648
• DOI: 10.1016/j.jphs.2018.09.001

A benzofuroquinolinium derivative that exhibits excellent cell division inhibitory effect was discovered through cell-based screening approach. This compound possesses potent antimicrobial activity against both Gram-positive and Gram-negative bacteria including the drug-resistant strains. In addition, this compound is able to restore MRSA susceptibility to beta-lactam antibiotics. The biochemical results suggest that the compound inhibits bacterial cell division through the disruption of GTPase activity and the polymerization of FtsZ, which is probably the mechanism of antibacterial activity.