RESUMO
According to the current understanding, the hyperactivation of platelets may lead to increased intravascular coagulation and thrombosis. Today a relevant issue is the search for new anti-thrombotic agents that are able to modulate the activity of platelet receptors, thus, influence the processes of activation and aggregation of platelets. The aim of this study was to investigate the effects of newly synthesized thiosulfonate derivatives on platelet aggregation. The activity of the compounds was tested in vitro using platelet-rich plasma. As a result of the screening test, structural formulas of four agents with high antiaggregative activity were established. These compounds inhibited ADP- and collagen-induced platelet aggregation in a dose-dependent manner. Two of these compounds were shown to be more effective inhibitors of aggregation induced by ADP (IC50 - 8-10 µM), as well as collagen (IC50 - 1.5-2.0 µM).
Assuntos
Plaquetas/efeitos dos fármacos , Inibidores da Agregação Plaquetária/síntese química , Agregação Plaquetária/efeitos dos fármacos , Ácidos Tiossulfônicos/síntese química , Animais , Células Cultivadas , Relação Dose-Resposta a Droga , Descoberta de Drogas , Ésteres , Estrutura Molecular , Inibidores da Agregação Plaquetária/química , Inibidores da Agregação Plaquetária/farmacologia , Plasma Rico em Plaquetas/citologia , Coelhos , Relação Estrutura-Atividade , Ácidos Tiossulfônicos/química , Ácidos Tiossulfônicos/farmacologiaRESUMO
The influence of novel biologically active substance potassium 4-toluenethiosulfonate in concentration of 4 x 10(-5) M on the changes of electrophysiological parameters of embryonic cells in early development of fish (Misgurnus fossilis L.) was investigated including the changes of membrane potential (TMP) and enzyme activity of plasmatic membranes of loach embryos during the period of synchronous division of blastomers in the early period of development. The evaluation of influence of these matters was studied and aperiodic changes of the level of TMP were shown. The diminishing of amplitude in every period by 7/12 mV and diminishing of growth of maximal values of vibrations of TMP by 39 mV in comparison to control was noticed. It was related to inhibition of some biosynthetic processes and results in the decline of activity of membrane enzyme (Na+, K(+)-ATPase) by 75.5 +/- 4.1% and 78.4 +/- 10.4% both at the action of high (4 x 10(-3) M) and low (4 x 10(-9) M) concentrations, accordingly, at first hours of development with subsequent renewal of its activity to the level of control only for the actions of low concentration.
