Synthesis of diacylglycerol analogues as potential second-messenger antagonists and inhibitors of protein kinase C.
A series of analogues of diacylglycerol has been prepared and tested as inhibitors of protein kinase C (PKC). The diketone analogues, 10-hydroxymethyl-8,13-eicosanedione (24), 10-acetoxymethyl-8,13-eicosanedione (25), and 10-methoxymethyl-8,13-eicosanedione (26) each inhibited PKC activated by 2-O-acetyl-1-O-oleoylglycerol. Compound 24 was the most effective inhibitor of the growth of MR4 and HT29 cells in culture, and 26 was more effective than 24 against HL60 cells.
Briggs
J C
JC
School of Chemical Sciences, University of East Anglia, Norwich, United Kingdom.
Haines
A H
AH
Taylor
R J
RJ
Dawson
A P
AP
Gibson
I
I
Hook
J
J
Lloyd
A
A
Meiners
S
S
D000818:Animals; D001681:Biological Assay; D004075:Diglycerides / Q000138:chemical synthesis*; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D015394:Molecular Structure; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D051381:Rats; D015290:Second Messenger Systems / Q000502:physiology*; D013237:Stereoisomerism; D014407:Tumor Cells, Cultured
D004075:Diglycerides; D011493:Protein Kinase C