On the inhibitory potency of imidazole and its derivatives on thromboxane synthetase

• Published in: Biochemical and biophysical research communications Vol. 80; no. 1; pp. 236 - 242
• Main Authors: Tai, Hsin-Hsiung, Yuan, Barbara
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 13.01.1978
• Subjects: Animals; Blood Platelets - enzymology; Imidazoles - pharmacology; Kinetics; Lung - enzymology; Microsomes - enzymology; Oxidoreductases - antagonists & inhibitors; Prostaglandins - biosynthesis; Radioimmunoassay; Sheep; Structure-Activity Relationship; Thromboxane-A Synthase - antagonists & inhibitors
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/0006-291X(78)91128-2

The relative inhibitory potency of imidazole and derivatives on thromboxane synthetase from human platelets was found to be increased by substitution of the 1-position and abolished in other positions. The potency of 1-substituted imidazoles was increased as the side chain became more hydrophobic. Among the imidazole derivatives tested 1-nonyl-imidazole and 1-(2-isopropyl phenyl)-imidazole showed the highest potency with I 50 in the range of 10 −8 M. Inhibition by imidazole and its derivatives appeared to be very specific for thromboxane synthetase since other enzymes in prostaglandin endoperoxide metabolism were not affected. Kinetic studies indicated that inhibition was competitive with respect to prostaglandin endoperoxide substrate.