Abstract
Natural living cell membrane phospholipids undergo rapid and continuous turnover that provides essential signalling pathways controlling cell survival. Derived from (lyso)phosphatidylcholine, alkylphopspholipids (APL) were synthesized as metabolically stable analogues 50 years ago. The nature of the chemical structure of APLs allows them to be inserted into membranes easily and partition into the membrane bilayers according to the degree of unsaturation of phospholipid alkyl chains. In an effort to overcome the severe side effects of existing anti‐tumour drugs, novel APLs with variations in alkyl side chain length, glycerol backbone, ester versus ether bonds, and different polar headgroups were developed to combine high anti‐proliferative capacity with reduced cytotoxicity. The platelet activating factor (PAF) is a natural alkylphospholipid. Substituting the sn‐2 position of platelet activating factor with an ether linked C2 spacer coupled to inositol created Inositol‐C2‐PAF. The effects of Inositol‐C2‐PAF can be divided into short‐term and long‐term effects. Short‐term effects include the inhibition of phosphorylation events, resulting in inhibition of cell proliferation and reduced cell migration. Long‐term effects of Inositol‐C2‐PAF, which are characterised by changes in gene expression, include up‐regulation of biological processes linked to cell differentiation or system development.Inspired by the natural phospholipid platelet activating factor (PAF) derivatives are shown, that intercalate in plasma membranes and at sub‐toxic concentrations disturb plasma membrane microdomain composition and/or intracellular responses.
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