Synthesis and effects of 3-methylthiopropanoyl thiolesters of lipoic acid, methional metabolite mimics.
6S,8S-Bis(3-methylthiopropanoyl) thiolesters of lipoic acid were synthesized with the carboxyl moiety of lipoate modified as methyl or water soluble choline esters. Evaluation on different cell lines in culture showed that they possessed modest antiproliferative activity. However, the 6-fold decrease in IC50 (from 270 to 45 microM) observed with the water soluble 6S,8S-bis(3-methylthiopropenoyl) thiolester dehydro derivative on a human epithelial prostate cancer cell line (DU145) argues in favor of 3-methylthiopropanoyl metabolites as endogenous growth regulatory (apoptogenic) compounds derived from methionine.
Courvoisier
Celine
C
LCO1, UMR 5181 (cpe) UCB Lyon 1, 43 bd du 11 nov 1918, 69622 Villeurbanne cedex, France.
Paret
Marie Julie
MJ
Chantepie
Jacqueline
J
Goré
Jacques
J
Fournet
Guy
G
Quash
Gerard
G
D000447:Aldehydes / Q000737:chemistry* / Q000378:metabolism; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D004952:Esters / Q000138:chemical synthesis* / Q000494:pharmacology; D006801:Humans; D020128:Inhibitory Concentration 50; D008297:Male; D008715:Methionine / Q000737:chemistry; D018716:Molecular Mimicry; D011422:Propionates / Q000737:chemistry*; D011471:Prostatic Neoplasms / Q000473:pathology; D013438:Sulfhydryl Compounds / Q000737:chemistry; D008063:Thioctic Acid / Q000138:chemical synthesis* / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000447:Aldehydes; D000970:Antineoplastic Agents; D004952:Esters; D011422:Propionates; D013438:Sulfhydryl Compounds; C008390:methional; C017526:3-methylthiopropionate; D008063:Thioctic Acid; D008715:Methionine