Semisynthesis of alpha-methyl-gamma-lactones and in vitro evaluation of their activity on protein farnesyltransferase.
The semisynthesis of xanthanolide derivatives is reported from xanthinin and 4-epi-isoxanthanol, two sesquiterpene lactones isolated from the crude chloroformic extract of the leaves of Xanthium macrocarpum DC. (Asteraceae) by liquid/liquid chromatography. In vitro evaluation of their protein farnesyltransferase (PFTase) inhibitory activity has been investigated. In contrast to other biological activities of xanthanolides, PFTase inhibition is not associated with the presence of the potentially toxic alpha-methylene-gamma-lactone function.
Pinel
Benoit
B
IFR 149 QUASAV, Laboratoire SONAS, UFR des Sciences Pharmaceutiques et Ingénierie de la Santé, Angers, France.
Dubois
Joëlle
J
Séraphin
Denis
D
Richomme
Pascal
P
D019883:Alkyl and Aryl Transferases / Q000037:antagonists & inhibitors*; D002725:Chloroform / Q000737:chemistry*; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000473:pathology; D057075:Enzyme Assays; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D045325:HCT116 Cells; D006801:Humans; D007783:Lactones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D010936:Plant Extracts / Q000737:chemistry*; D018515:Plant Leaves / Q000737:chemistry*; D012717:Sesquiterpenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D012997:Solvents / Q000737:chemistry; D031210:Xanthium / Q000737:chemistry*
D004791:Enzyme Inhibitors; D007783:Lactones; D010936:Plant Extracts; D012717:Sesquiterpenes; D012997:Solvents; D002725:Chloroform; D019883:Alkyl and Aryl Transferases; C064911:p21(ras) farnesyl-protein transferase