Exocarpic acid inhibits mycolic acid biosynthesis in Mycobacterium tuberculosis.
Exocarpic acid (13 E-octadecene-9,11-diynoic acid) from Exocarpos latifolius R.Br. (Santalaceae) was previously shown to have specific antimycobacterial activity. Microarray data suggested inhibition of fatty acid metabolism as a potential mode of action. Experiments designed to elucidate the mechanism of action showed that exocarpic acid was effective at inhibition of mycolic acid biosynthesis and did not act by dissipating the proton gradient in treated M. tuberculosis. Amide derivatives of exocarpic acid displayed similar properties to exocarpic acid, while other polyacetylenic fatty acids varied in their effects on mycolic acid biosynthesis.
Koch
Michael
M
Department of Pharmacology and Toxicology, University of Utah, Salt Lake City, Utah 84112, USA.
Bugni
Tim S
TS
Sondossi
Mohammad
M
Ireland
Chris M
CM
Barrows
Louis R
LR
D000995:Antitubercular Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D053280:Diynes / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D005231:Fatty Acids, Unsaturated / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000378:metabolism; D009171:Mycolic Acids / Q000378:metabolism*; D029630:Santalaceae / Q000737:chemistry
D000995:Antitubercular Agents; D053280:Diynes; D005231:Fatty Acids, Unsaturated; D009171:Mycolic Acids; C547032:exocarpic acid