Artículos de revistas
Discovery of antibiotic (E)-3-(3-carboxyphenyl)-2-(4-cyanostyryl)quinazolin-4(3H)-one
Fecha
2015-02Registro en:
Bouley, Renee; Kumarasiri, Malika; Peng, Zhihong; Otero, Lisandro Horacio; Song, Wei; et al.; Discovery of antibiotic (E)-3-(3-carboxyphenyl)-2-(4-cyanostyryl)quinazolin-4(3H)-one; American Chemical Society; Journal Of The American Chemical Society; 137; 5; 2-2015; 1738-1741
1520-5126
Autor
Bouley, Renee
Kumarasiri, Malika
Peng, Zhihong
Otero, Lisandro Horacio
Song, Wei
Suckow, Mark A.
Schroeder, Valerie A.
Wolter, William R.
Lastochkin, Elena
Antunes, Nuno T.
Pi, Hualiang
Vakulenko, Sergei
Hermoso, Juan Antonio
Chang, Mayland
Mobashery, Shahriar
Resumen
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.