| Literature DB >> 25629446 |
Renee Bouley1, Malika Kumarasiri, Zhihong Peng, Lisandro H Otero, Wei Song, Mark A Suckow, Valerie A Schroeder, William R Wolter, Elena Lastochkin, Nuno T Antunes, Hualiang Pi, Sergei Vakulenko, Juan A Hermoso, Mayland Chang, Shahriar Mobashery.
Abstract
In the face of the clinical challenge posed by resistant bacteria, the present needs for novel classes of antibiotics are genuine. In silico docking and screening, followed by chemical synthesis of a library of quinazolinones, led to the discovery of (E)-3-(3-carboxyphenyl)-2-(4-cyanostyryl)quinazolin-4(3H)-one (compound 2) as an antibiotic effective in vivo against methicillin-resistant Staphylococcus aureus (MRSA). This antibiotic impairs cell-wall biosynthesis as documented by functional assays, showing binding of 2 to penicillin-binding protein (PBP) 2a. We document that the antibiotic also inhibits PBP1 of S. aureus, indicating a broad targeting of structurally similar PBPs by this antibiotic. This class of antibiotics holds promise in fighting MRSA infections.Entities:
Mesh：
Substances：
Year: 2015 PMID： 25629446 PMCID： PMC4607046 DOI： 10.1021/jacs.5b00056
Source DB: PubMed Journal: J Am Chem Soc ISSN： 0002-7863 Impact factor: 15.419