Synthesis and biological activity of hydroxylated derivatives of linoleic acid and conjugated linoleic acids.
Allylic hydroxylated derivatives of the C18 unsaturated fatty acids were prepared from linoleic acid (LA) and conjugated linoleic acids (CLAs). The reaction of LA methyl ester with selenium dioxide (SeO(2)) gave mono-hydroxylated derivatives, 13-hydroxy-9Z,11E-octadecadienoic acid, 13-hydroxy-9E,11E-octadecadienoic acid, 9-hydroxy-10E,12Z-octadecadienoic acid and 9-hydroxy-10E,12E-octadecadienoic acid methyl esters. In contrast, the reaction of CLA methyl ester with SeO(2) gave di-hydroxylated derivatives as novel products including, erythro-12,13-dihydroxy-10E-octadecenoic acid, erythro-11,12-dihydroxy-9E-octadecenoic acid, erythro-10,11-dihydroxy-12E-octadecenoic acid and erythro-9,10-dihydroxy-11E-octadecenoic acid methyl esters. These products were purified by normal-phase short column vacuum chromatography followed by high-performance liquid chromatography (HPLC). Their chemical structures were characterized by liquid chromatography-mass spectrometry (LC-MS) and nuclear magnetic resonance spectroscopy (NMR). The allylic hydroxylated derivatives of LA and CLA exhibited moderate in vitro cytotoxicity against a panel of human cancer cell lines including chronic myelogenous leukemia K562, myeloma RPMI8226, hepatocellular carcinoma HepG2 and breast adenocarcinoma MCF-7 cells (IC(50) 10-75 microM). The allylic hydroxylated derivatives of LA and CLA also showed toxicity to brine shrimp with LD(50) values in the range of 2.30-13.8 microM. However these compounds showed insignificant toxicity to honeybee at doses up to 100 microg/bee.
Li
Zhen
Z
School of Biotechnology, Southern Medical University, Guangzhou, Guangdong Province 510515, PR China.
Tran
Van H
VH
Duke
Rujee K
RK
Ng
Michelle C H
MC
Yang
Depo
D
Duke
Colin C
CC
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001156:Artemia / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D006900:Hydroxylation; D007928:Lethal Dose 50; D019787:Linoleic Acid / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D044243:Linoleic Acids, Conjugated / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D018036:Selenium Compounds / Q000737:chemistry; D064588:Selenium Oxides
D000970:Antineoplastic Agents; D044243:Linoleic Acids, Conjugated; D018036:Selenium Compounds; D064588:Selenium Oxides; D019787:Linoleic Acid