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 language | English |
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Pages (from-to) | 2131-2140 |
Number of pages | 10 |
Journal | Journal of Chemical Information and Modeling |
Volume | 53 |
Issue number | 8 |
DOIs | |
Publication status | Published - 26 Aug 2013 |
ASJC Scopus subject areas
- General Chemistry
- General Chemical Engineering
- Computer Science Applications
- Library and Information Sciences