Grand Valley State University, Chemistry, Allendale, MI 49401
β-lactams are the most widely prescribed class of antibiotics. However, their continued utility is threatened by the expression of β-lactamase enzymes, which hydrolyze the defining lactam ring of these antibiotics, rendering them useless. Current clinical inhibitors for these enzymes also contain a lactam ring, allowing resistance to develop rapidly. Inhibitors that do not resemble β-lactams would require bacteria to develop novel resistance mechanisms. Previous research identified a novel, non-β-lactam inhibitor for the class C β-lactamase AmpC (3-[(4-chloroanilino)sulfonyl]thiophene-2-carboxylic acid; KI 26 mM). In an effort to improve the binding affinity of this inhibitor, a series of sulfonylthiophene carboxylic acid derivatives with varying carbon chain spacer lengths were synthesized and tested for inhibition of AmpC.
[Abstract (DOC)]