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
ISSN: 1932-6203
DOI: 10.1371/journal.pone.0097514
Appears in Collections:Journal/Magazine Article

Access
View full-text via PolyU eLinks SFX Query
Show full item record

SCOPUSTM   
Citations

14
Last Week
0
Last month
0
Citations as of Apr 22, 2017

WEB OF SCIENCETM
Citations

12
Last Week
0
Last month
0
Citations as of Apr 18, 2017

Page view(s)

42
Last Week
7
Last month
Checked on Apr 23, 2017

Google ScholarTM

Check

Altmetric



Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.