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

Fung Yi Chan, Ning Sun, Marco A.C. Neves, Polo Chun Hung Lam, Wai Hong Chung, Lai King Wong, Ho Yin Chow, Dik Lung Ma, Pak Ho Chan, Yun Chung Leung, Tak Hang Chan, Ruben Abagyan, Kwok Yin Wong

Research output: Journal article publicationJournal articleAcademic researchpeer-review

54 Citations (Scopus)

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 IC50and 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.
Original languageEnglish
Pages (from-to)2131-2140
Number of pages10
JournalJournal of Chemical Information and Modeling
Volume53
Issue number8
DOIs
Publication statusPublished - 26 Aug 2013

ASJC Scopus subject areas

  • Chemistry(all)
  • Chemical Engineering(all)
  • Computer Science Applications
  • Library and Information Sciences

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