Inhibition of leukotriene and thromboxane biosynthesis by a 9-(4-chlorophenyl) analogue of arachidonic acid.
The synthesis of 9-(4-chlorophenyl)-7,7-dimethyl-5(Z), 8-nonadienoic acid (7) and its methyl ester 6, and their effects on arachidonic acid metabolism in vitro are described. The IC50 values of 19.6 and 20.6 microM were observed for inhibition of leukotriene synthesis in human granulocytes for 6 and 7, respectively. Additionally, the compounds inhibited thromboxane B2 (TxB2) synthesis, with respective IC50 values of 6.1 and 20 microM, while producing pronounced 3-8-fold increases in PGE2 synthesis in human mononuclear cells. Increased PGE2 synthesis may have reflected shunting of free arachidonic acid substrate at the thromboxane synthetase and endoperoxide E isomerase branchpoint of arachidonic acid metabolism.
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D015232:Dinoprostone; D005231:Fatty Acids, Unsaturated / Q000096:biosynthesis* / Q000494:pharmacology*; D006098:Granulocytes / Q000187:drug effects / Q000378:metabolism; D006168:Guinea Pigs; D006801:Humans; D066298:In Vitro Techniques; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D016859:Lipoxygenase Inhibitors; D008168:Lung / Q000187:drug effects; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D011458:Prostaglandins E / Q000096:biosynthesis; D013929:Thromboxane B2 / Q000096:biosynthesis
D001095:Arachidonic Acids; D005231:Fatty Acids, Unsaturated; D016859:Lipoxygenase Inhibitors; D011458:Prostaglandins E; C055648:9-(4-chlorophenyl)-7,7-dimethyl-5,8-nonadienoic acid; C055649:9-(4-chlorophenyl) 7,7-dimethyl-5,8-nonadienoic acid methyl ester; D016718:Arachidonic Acid; D013929:Thromboxane B2; D015232:Dinoprostone