Effect of side-chain substitution of a CH2 group by sulfur on the antimicrobial activity of natural penicillins and cephalosporins.

Abstract
The S-carboxymethyl-D-cysteine side-chain analogs of cephalosporin C and deacetoxycephalosporin C were found to have markedly increased in vitro activity against Gram-positive and Gram-negative bacteria compared to the natural antibiotics. The S-carboxymethyl-L-cysteine analogs were less active than the S-carboxymethyl-D-cysteine analogs but against most organisms tested, still more active than the natural compounds. The effect of replacement of CH2 with S was less dramatic in the case of penicillin N and isopenicillin N. The S-carboxymethyl-D-cysteine analog of deacetoxycephalosporin C was found to be orally available in rats.