Evaluation of penicillin-based inhibitors of the class A and B β-lactamases from Bacillus anthracis

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• 作者：Beharry ; Zanna ; Chen ; Hansong ; Gadhachanda ; Venkat R. ; Buynak ; John D. ; Palzkill ; Timothy
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：2004
• 出版时间：January 16, 2004
• 年：2004
• 卷：313
• 期：3
• 页码：541-545
• 全文大小：150 K

文摘

Bacillus anthracis contains a class A (Bla1) and class B (Bla2) β-lactamase, which confer resistance to β-lactam antibiotics when expressed in Escherichia coli. In an effort to find new β-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 K_i