Please use this identifier to cite or link to this item: http://hdl.handle.net/10397/16174
Title: Rational design of berberine-based FtsZ inhibitors with broad-spectrum antibacterial activity
Authors: Sun, N 
Chan, FY 
Lu, YJ 
Neves, MAC
Lui, HK 
Wang, Y 
Chow, KY 
Chan, KF 
Yan, SC 
Leung, YC 
Abagyan, R
Chan, TH 
Wong, KY 
Issue Date: 2014
Publisher: Public Library of Science
Source: PLoS one, 2014, v. 9, no. 5, e97514 How to cite?
Journal: PLoS one 
Abstract: Inhibition of the functional activity of Filamenting temperature-sensitive mutant Z (FtsZ) protein, an essential and highly conserved bacterial cytokinesis protein, is a promising approach for the development of a new class of antibacterial agents. Berberine, a benzylisoquinoline alkaloid widely used in traditional Chinese and native American medicines for its antimicrobial properties, has been recently reported to inhibit FtsZ. Using a combination of in silico structure-based design and in vitro biological assays, 9-phenoxyalkyl berberine derivatives were identified as potent FtsZ inhibitors. Compared to the parent compound berberine, the derivatives showed a significant enhancement of antibacterial activity against clinically relevant bacteria, and an improved potency against the GTPase activity and polymerization of FtsZ. The most potent compound 2 strongly inhibited the proliferation of Gram-positive bacteria, including methicillin-resistant S. aureus and vancomycin-resistant E. faecium, with MIC values between 2 and 4 μg/mL, and was active against the Gram-negative E. coli and K. pneumoniae, with MIC values of 32 and 64 mg/mL respectively. The compound perturbed the formation of cytokinetic Z-ring in E. coli. Also, the compound interfered with in vitro polymerization of S. aureus FtsZ. Taken together, the chemical modification of berberine with 9-phenoxyalkyl substituent groups greatly improved the antibacterial activity via targeting FtsZ.
URI: http://hdl.handle.net/10397/16174
EISSN: 1932-6203
DOI: 10.1371/journal.pone.0097514
Rights: © 2014 Sun et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
The following publication Sun N, Chan FY, Lu YJ, Neves MAC, Lui HK, et al. (2014) Rational Design of Berberine-Based FtsZ Inhibitors with Broad-Spectrum Antibacterial Activity, PLOS ONE 9(5): e97514 is available at https://doi.org/10.1371/journal.pone.0097514
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