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Synthesis of diacylglycerol analogues as potential second-messenger antagonists and inhibitors of protein kinase C. 1992
J C Briggs, and
A H Haines, and
R J Taylor, and
A P Dawson, and
I Gibson, and
J Hook, and
A Lloyd, and
S Meiners
School of Chemical Sciences, University of East Anglia, Norwich, United Kingdom.
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.
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