Evaluation of penicillin-based inhibitors of the class A and B beta-lactamases from Bacillus anthracis.
Biochem Biophys Res Commun
; 313(3): 541-5, 2004 Jan 16.
Article
en En
| MEDLINE
| ID: mdl-14697223
ABSTRACT
Bacillus anthracis contains a class A (Bla1) and class B (Bla2) beta-lactamase, which confer resistance to beta-lactam antibiotics when expressed in Escherichia coli. In an effort to find new beta-lactamase inhibitors, several penicillin derivatives have been evaluated including experimental compounds incorporating a 6-mercaptomethyl group or a 6-pyridylmethylidene group, along with clavulanate and tazobactam, as inhibitors against Bla1 and Bla2. The 6-mercaptomethyl-substituted penicillins showed much greater activity against the zinc-containing Bla2 than Bla1. The compound that incorporated a 6-pyridylmethylidene substituent and a catecholic substituent at the 2' position was the most effective inhibitor of Bla1 with Ki=0.057 microM. Inhibitors containing iron-chelating functional groups have previously been shown to work in combination with antibiotics to inhibit growth of antibiotic-resistant bacteria expressing beta-lactamase. The development of similar compounds, incorporating these types of substituents, may help overcome resistance to currently used antibiotics.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Penicilinas
/
Bacillus anthracis
/
Beta-Lactamasas
/
Ácido Penicilánico
/
Antibacterianos
Idioma:
En
Revista:
Biochem Biophys Res Commun
Año:
2004
Tipo del documento:
Article
País de afiliación:
Estados Unidos