Development of a screening assay for the in vitro evaluation of thromboxane A2 synthase inhibitors.
Inhibitors of thromboxane A2 (TxA2) synthase are regarded as potentially useful agents in the treatment of cardiovascular diseases and in the prevention of tumour cell metastases. We report here a novel in vitro assay for the evaluation of TxA2 synthase inhibitors. For the determination of inhibitory activity, malondialdehyde (MDA) formation by TxA2 synthase in whole blood was utilized. After reaction with thiobarbituric acid MDA was quantified spectrofluorimetrically. The blank value was obtained by incubation with a selective TxA2 synthase inhibitor. For the screening of compounds the simple MDA assay represents an alternative to the rather expensive and time consuming radioimmunoassay, HPLC and TLC methods. Only for compounds which have been shown to be good inhibitors in the MDA assay should a radioimmunoassay for selective inhibition of TxA2 synthase be performed.
Ledergerber
D
D
Fachrichtung 12.1 Pharmazeutische Chemie, Universität des Saarlandes, Saarbrücken, Germany.
Hartmann
R W
RW
D001792:Blood Platelets / Q000201:enzymology; D015232:Dinoprostone / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D004791:Enzyme Inhibitors / Q000097:blood* / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D008315:Malondialdehyde / Q000032:analysis / Q000378:metabolism; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors* / Q000097:blood
D004791:Enzyme Inhibitors; D007093:Imidazoles; C029166:dazoxiben; D008315:Malondialdehyde; D013930:Thromboxane-A Synthase; D015232:Dinoprostone