| Structural highlights
Publication Abstract from PubMed
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.
Discovery of Antibiotic (E)-3-(3-Carboxyphenyl)-2-(4-cyanostyryl)quinazolin-4(3H)-one.,Bouley R, Kumarasiri M, Peng Z, Otero LH, Song W, Suckow MA, Schroeder VA, Wolter WR, Lastochkin E, Antunes NT, Pi H, Vakulenko S, Hermoso JA, Chang M, Mobashery S J Am Chem Soc. 2015 Feb 11;137(5):1738-41. doi: 10.1021/jacs.5b00056. Epub 2015, Feb 2. PMID:25629446[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Bouley R, Kumarasiri M, Peng Z, Otero LH, Song W, Suckow MA, Schroeder VA, Wolter WR, Lastochkin E, Antunes NT, Pi H, Vakulenko S, Hermoso JA, Chang M, Mobashery S. Discovery of Antibiotic (E)-3-(3-Carboxyphenyl)-2-(4-cyanostyryl)quinazolin-4(3H)-one. J Am Chem Soc. 2015 Feb 11;137(5):1738-41. doi: 10.1021/jacs.5b00056. Epub 2015, Feb 2. PMID:25629446 doi:http://dx.doi.org/10.1021/jacs.5b00056
|
