Please use this identifier to cite or link to this item: http://hdl.handle.net/10397/81554
Title: First-in-class inhibitors targeting the interaction between bacterial RNA polymerase and sigma initiation factor affect the viability and toxin release of streptococcus pneumoniae
Authors: Ye, J 
Chu, AJ
Lin, L
Yang, X
Ma, C 
Keywords: Antimicrobial discovery
Inhibitor
RNA polymerase
Sigma factor
Transcription
Issue Date: 2019
Publisher: Molecular Diversity Preservation International (MDPI)
Source: Molecules, 2019, v. 24, no. 16, 2902 How to cite?
Journal: Molecules 
Abstract: Novel antimicrobial classes are in desperate need for clinical management of infections caused by increasingly prevalent multi-drug resistant pathogens. The protein-protein interaction between bacterial RNA polymerase (RNAP) and the housekeeping sigma initiation factor is essential to transcription and bacterial viability. It also presents a potential target for antimicrobial discovery, for which a hit compound (C3) was previously identified from a pharmacophore modelbased in silico screen. In this study, the hit compound was experimentally assessed with some rationally designed derivatives for the antimicrobial activities, in particular against Streptococcus pneumoniae and other pathogens. One compound, C3-005, shows dramatically improved activity against pneumococci compared to C3. C3-005 also attenuates S. pneumoniae toxin production more strongly than existing classes of antibiotics tested. Here we demonstrate a newly validated antimicrobial agent to address an overlooked target in the hit-to-lead process, which may pave the way for further antimicrobial development.
URI: http://hdl.handle.net/10397/81554
ISSN: 1420-3049
DOI: 10.3390/molecules24162902
Rights: © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
The following publication Ye J, Chu AJ, Lin L, Yang X, Ma C. First-In-Class Inhibitors Targeting the Interaction between Bacterial RNA Polymerase and Sigma Initiation Factor Affect the Viability and Toxin Release of Streptococcus pneumoniae. Molecules. 2019; 24(16):2902, is available at https://doi.org/10.3390/molecules24162902
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