Benzopyranones with retro-amide side chains as (inhibitory) beta-lactamase substrates

Bioorganic & Medicinal Chemistry Letters
S A AdediranR F Pratt

Abstract

3-(N-Benzylcarbamoyl)-7-carboxy-3, 4-dihydro-2H-1-benzo-pyran-2-one and its 8-carboxy analogue have been synthesized and evaluated as potential (inhibitory) substrates of beta-lactam-recognizing enzymes. These compounds are bicyclic delta-lactones with retro-amide (with respect to classical beta-lactams) side chains. They were found to be comparably effective as substrates of typical class A, C and D beta-lactamases as analogous benzopyranones bearing 'normal' amide side chains. The new 8-carboxy derivative, however, formed a much more (1000-fold) tightly-bound acyl-enzyme with a class C beta-lactamase than did its 'normal' analogue, and thus provides a structural lead to new inhibitors of this class of beta-lactamase.

References

Mar 26, 1999·Bioorganic & Medicinal Chemistry Letters·S A AdediranM Wakselman
May 30, 2001·Bioorganic & Medicinal Chemistry·S A AdediranM Wakselman
Oct 25, 2001·The Journal of Organic Chemistry·D. CabaretM. Wakselman
Jun 5, 2003·Biochemistry·D CabaretM Wakselman

❮ Previous
Next ❯

Citations

Sep 21, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Jan ZitkoMartin Doležal

❮ Previous
Next ❯

Related Concepts

Related Feeds

Beta-lactamase Inhibitors (ASM)

Beta-lactamase inhibitors are a class of antibiotics that inhibit beta-lactamases, a family of enzymes involved in bacterial resistance to beta-lactam antibiotics. Here is the latest research.

Beta-lactamase Inhibitors

Beta-lactamase inhibitors are a class of antibiotics that inhibit beta-lactamases, a family of enzymes involved in bacterial resistance to beta-lactam antibiotics. Here is the latest research.