RESUMO
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.
Assuntos
Ácido Araquidônico/farmacologia , Plaquetas/metabolismo , Inibidores de Ciclo-Oxigenase/farmacologia , Cetonas/farmacologia , Malondialdeído/sangue , Compostos de Sulfidrila/farmacologia , Ácido Araquidônico/antagonistas & inibidores , Aspirina/farmacologia , Plaquetas/efeitos dos fármacos , Cristalografia por Raios X , Inibidores de Ciclo-Oxigenase/síntese química , Inibidores de Ciclo-Oxigenase/química , Humanos , Técnicas In Vitro , Cetonas/síntese química , Cetonas/química , Cinética , Modelos Moleculares , Estrutura Molecular , Compostos de Sulfidrila/síntese química , Compostos de Sulfidrila/químicaRESUMO
Some new aryl thiopyranylidene ketones and benzylidene indanones with various substituents on the benzene ring were synthesized and their inhibitory activities in vitro on human platelet aggregation were assayed. The 2-[(2,5-dimethoxyphenyl)methylene] indan-1-one is the most potent inhibitor (about seventeen times more active than aspirin, against arachidonic acid, and twenty four times against collagen).
Assuntos
Indanos/síntese química , Indenos/síntese química , Inibidores da Agregação Plaquetária/síntese química , Piranos/síntese química , Fenômenos Químicos , Química , Humanos , Técnicas In Vitro , Indanos/farmacologia , Cetonas/síntese química , Cetonas/farmacologia , Inibidores da Agregação Plaquetária/farmacologia , Piranos/farmacologiaRESUMO
New 3,4-dihydro-2-arylidene-1-(2H)-naphthalenones derivatives were synthesized and their inhibitory effects in vitro on the arachidonic acid-induced platelet aggregation were evaluated. The 3,4-dihydro-2-[(2,5-dimethoxyphenyl)methylene]-1-(2H)-naphthalenone++ + exhibits the most potent antiaggregating activity; compared with aspirin this compound is three times more active. Its crystal structure has been determined.
