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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

PAF-agonistic and -antagonistic behaviour of new synthetic ether phospholipids. II. Relationships between chemical structure and inhibition of PAF-induced human platelet activation.

A series of 30 newly synthesised racemic ether phospholipids was evaluated for PAF-antagonistic action on human blood platelets in vitro. The chemical structure of these compounds was derived from the 1-O-hexadecyl-2-O-ethyl-glycero-3-phosphoric acid 4-(N,N-dimethylamino)pyridinium ethylester which was recently characterised as a PAF-specific antagonist. Anti-PAF effects were demonstrated by means of an aggregation and a binding assay. The inhibition was concentration-dependent and of competitive type. KB-values for inhibiting platelet aggregation in plasma were greater than or equal to 0.3 mumol/l. The most effective antagonists were 3-10 times more effective in comparison with the ginkgolide BN 52021. Structure-activity relationship studies showed the 4-dimethylaminopyridine moiety in the 3 position to be the ultimate structural requirement for expressing PAF-antagonistic activity. Moreover, a short-chain substituent in the 2 position and a distinct distance between the phosphate group and the onium center were found to be essential for high PAF-antagonistic activity.[1]


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