2024-03-28T22:23:29Zhttp://digital.csic.es/dspace-oai/requestoai:digital.csic.es:10261/1306112021-11-22T13:12:17Zcom_10261_34com_10261_5col_10261_287
Discovery of antibiotic (E)-3-(3-carboxyphenyl)-2-(4-cyanostyryl)quinazolin-4(3 H)-one
Bouley, R.
Kumarasiri, M.
Peng, Z.
Otero, L. H.
Song, W.
Suckow, M.A.
Schroeder, V.A.
Wolter, W.R.
Lastochkin, E.
Antunes, N.T.
Pi, H.
Vakulenko, S.
Hermoso, Juan A.
Chang, M.
Mobashery, S.
© 2015 American Chemical Society. 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.
Peer Reviewed
2016-03-30T13:48:09Z
2016-03-30T13:48:09Z
2015
2016-03-30T13:48:12Z
artículo
http://purl.org/coar/resource_type/c_6501
doi: 10.1021/jacs.5b00056
issn: 1520-5126
Journal of the American Chemical Society 137: 1738- 1741 (2015)
http://hdl.handle.net/10261/130611
10.1021/jacs.5b00056
25629446
Sí
none
American Chemical Society