Synthesis and evaluation of analogues of S-adenosyl-L-methionine, as inhibitors of the E. coli cyclopropane fatty acid synthase

Christine Guérard; Maud Bréard; Fabienne Courtois; Thierry Drujon; Olivier Ploux

doi:10.1016/j.bmcl.2004.01.051

Synthesis and evaluation of analogues of S-adenosyl-L-methionine, as inhibitors of the E. coli cyclopropane fatty acid synthase

Bioorg Med Chem Lett. 2004 Apr 5;14(7):1661-4. doi: 10.1016/j.bmcl.2004.01.051.

Authors

Christine Guérard¹, Maud Bréard, Fabienne Courtois, Thierry Drujon, Olivier Ploux

Affiliation

¹ UMR 7613 CNRS, Université Pierre et Marie Curie, 4 place Jussieu, F-75252 Paris cedex 05, France.

PMID: 15026045
DOI: 10.1016/j.bmcl.2004.01.051

Abstract

Analogues of S-adenosyl-L-methionine were synthesized and evaluated as inhibitors of the purified E. coli cyclopropane fatty acid synthase, a model for M. tuberculosis cyclopropane synthases that are potential targets for antituberculous drugs. Our results show that the presence of the adenosine moiety, in the inhibitor, is required for strong binding, but that the sulfonium charge is less important. The best inhibitors found were S-adenosyl-l-homocysteine and its sulfoxides.

MeSH terms

Drug Evaluation, Preclinical / methods
Enzyme Inhibitors / chemical synthesis*
Enzyme Inhibitors / metabolism
Enzyme Inhibitors / pharmacology
Escherichia coli Proteins / antagonists & inhibitors*
Escherichia coli Proteins / metabolism
Methyltransferases / antagonists & inhibitors*
Methyltransferases / metabolism
S-Adenosylmethionine / chemical synthesis*
S-Adenosylmethionine / metabolism
S-Adenosylmethionine / pharmacology

Substances

Enzyme Inhibitors
Escherichia coli Proteins
S-Adenosylmethionine
Methyltransferases
cyclopropane synthetase