Synthesis and biological evaluation of ether-linked derivatives of phosphatidylinositol.
The synthesis of two novel glycero-3-phosphoinositol ether lipid analogues, rac-1-O-octadecyl-2-O-methylglycero-3-phospho-myo-inositol 6 (an ether lipid analogue of rac-1-O-octadecyl-2-O-methylglycero-3-phosphocholine; ET-18-OMe) and rac-1-O-octadecyl-2-O-acetylglycero-3-phospho-myo-inositol 11 (an ether lipid analogue of platelet-activating factor), is described. The two target compounds and the synthetic intermediates were evaluated for inhibition of HL60, BG1, and BG3 human malignant cells in vitro and inhibition of protein kinase C. Tumor inhibitory activity was found for compounds 6 and 11 in all systems but not for their synthetic intermediates. However, compounds 6 and 11 as well as the synthetic intermediates 5 and 13, but not 9, exhibited protein kinase C inhibitory activity.
Ishaq
K S
KS
School of Pharmacy, Division of Medicinal Chemistry and Natural Products, University of North Carolina, Chapel Hill 27599.
Capobianco
M
M
Piantadosi
C
C
Noseda
A
A
Daniel
L W
LW
Modest
E J
EJ
D055598:Chemical Phenomena; D002621:Chemistry; D006801:Humans; D010716:Phosphatidylinositols / Q000138:chemical synthesis* / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D014407:Tumor Cells, Cultured / Q000187:drug effects*
D010716:Phosphatidylinositols; D011493:Protein Kinase C