Inhibition of thromboxane synthesis and platelet aggregation by pyridine and its derivatives.
Pyridine inhibited the conversion of PG endoperoxide to TXA2 catalyzed by TX synthetase from human platelet and swine lung microsomes. The inhibitory potency of pyridine is abolished by derivatizing pyridine at the 2-position but is increased by introducing hydrophobic substituents at 3- or 4-positions, with 3-substituted pyridines being the most potent inhibitors. Inhibition by pyridine and its derivatives was also selective, since other enzymes in the arachidonic acid cascade were not significantly affected. Pyridine and the active derivatives also inhibited human platelet aggregation induced by arachidonic acid or ADP.
D000818:Animals; D001792:Blood Platelets / Q000201:enzymology*; D006801:Humans; D007700:Kinetics; D008168:Lung / Q000201:enzymology*; D008861:Microsomes / Q000201:enzymology*; D010088:Oxidoreductases / Q000037:antagonists & inhibitors*; D010974:Platelet Aggregation / Q000187:drug effects*; D011725:Pyridines / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013552:Swine; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors*
D011725:Pyridines; D010088:Oxidoreductases; D013930:Thromboxane-A Synthase