Document Type

Journal Article

Authors

Fung-Yi Chan, Department of Applied Biology and Chemical Technology, State Key Laboratory of Chirosciences, Hong Kong Polytechnic University
Ning Sun, Department of Applied Biology and Chemical Technology, State Key Laboratory of Chirosciences, Hong Kong Polytechnic University
Marco A. C. Neves, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, MC 0747
Polo Chun-Hung Lam, Molsoft L.L.C
Wai-Hong Chung, Department of Applied Biology and Chemical Technology, State Key Laboratory of Chirosciences, Hong Kong Polytechnic University
Lai-King Wong, Department of Applied Biology and Chemical Technology, State Key Laboratory of Chirosciences, Hong Kong Polytechnic University
Ho-Yin Chow, Department of Applied Biology and Chemical Technology, State Key Laboratory of Chirosciences, Hong Kong Polytechnic University
Dik-Lung Ma, Department of Applied Biology and Chemical Technology, State Key Laboratory of Chirosciences, Hong Kong Polytechnic University
Pak-Ho Chan, Department of Applied Biology and Chemical Technology, State Key Laboratory of Chirosciences, Hong Kong Polytechnic University
Yun-Chung Leung, Department of Applied Biology and Chemical Technology, State Key Laboratory of Chirosciences, Hong Kong Polytechnic University
Tak-Hang Chan, Department of Applied Biology and Chemical Technology, State Key Laboratory of Chirosciences, Hong Kong Polytechnic University
Ruben Abagyan, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, MC 0747
Kwok-Yin Wong, Department of Applied Biology and Chemical Technology, State Key Laboratory of Chirosciences, Hong Kong Polytechnic University

Department/Unit

Department of Chemistry

Title

Identification of a new class of ftsz inhibitors by structure-based design and in vitro screening

Language

English

Abstract

The Filamenting temperature-sensitive mutant Z (FtsZ), an essential GTPase in bacterial cell division, is highly conserved among Gram-positive and Gram-negative bacteria and thus considered an attractive target to treat antibiotic-resistant bacterial infections. In this study, a new class of FtsZ inhibitors bearing the pyrimidine-quinuclidine scaffold was identified from structure-based virtual screening of natural product libraries. Iterative rounds of in silico studies and biological evaluation established the preliminary structure-activity relationships of the new compounds. Potent FtsZ inhibitors with low micromolar IC50 and antibacterial activity against S. aureus and E. coli were found. These findings support the use of virtual screening and structure-based design for the rational development of new antibacterial agents with innovative mechanisms of action. © 2013 American Chemical Society.

Publication Date

2013

Source Publication Title

Journal of Chemical Information and Modeling

Volume

53

Issue

8

Start Page

2131

End Page

2140

Publisher

American Chemical Society

DOI

10.1021/ci400203f

Link to Publisher's Edition

http://dx.doi.org/10.1021/ci400203f

ISSN (print)

15499596

ISSN (electronic)

1549960X

This document is currently not available here.

Share

COinS