Inhibitory effect of aryl thienyl-ketones and -thioketones on arachidonic acid-induced malondialdehyde formation in human platelets: biological data and molecular modelling.
A series of anti-thrombotic aryl thienyl-ketones and -thioketones was assayed in vitro for their inhibitory effect on malondialdehyde (MDA) production induced by arachidonic acid in human platelets. For several compounds MDA formation was strongly inhibited indicating that the anti-platelet target was situated on the cyclooxygenase pathway. A comparison between the inhibition constant Ki and the IC50 values revealed competitive inhibition kinetics. The molecular structure of one active compound was analysed by X-ray diffraction and theoretical calculations to provide information on its electronic and lipophilic properties.
Nuhrich
A
A
Laboratoire de Pharmacie Chimique et Chimie Thérapeutique, URA 605 CNRS, Faculté des Sciences Pharmaceutiques, Université de Bordeaux II, France.
Varache-Beranger
M
M
Carpy
A
A
Montagut
M
M
Devaux
G
G
D016718:Arachidonic Acid / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D001241:Aspirin / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D018360:Crystallography, X-Ray; D016861:Cyclooxygenase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D007659:Ketones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D007700:Kinetics; D008315:Malondialdehyde / Q000097:blood*; D008958:Models, Molecular; D015394:Molecular Structure; D013438:Sulfhydryl Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
D016861:Cyclooxygenase Inhibitors; D007659:Ketones; D013438:Sulfhydryl Compounds; D016718:Arachidonic Acid; D008315:Malondialdehyde; D001241:Aspirin