Open AccessNovel perspective substances with selective anti-aggregant action
Author(s) -
С. В. Киселев,
Киселёв Сергей Васильевич,
Л. Е. Никитина,
Никитина Лилия Евгеньевна,
М. М. Воронцова,
Воронцова Марина Минтдиновна,
R G Turaev,
Тураев Рамиль Габдельхакович
Publication year - 2013
Publication title -
kazanskij medicinskij žurnal
Language(s) - English
Resource type - Journals
eISSN - 2587-9359
pISSN - 0368-4814
DOI - 10.17816/kmj1923
Subject(s) - chemistry , partial thromboplastin time , hemostasis , coagulation , medicine
Aim. To study the influence of new sulfur-containing derivatives of β-pinene on the platelet aggregation ability and coagulant activity of human serum in vitro.Methods. A series of sulfides and sulfoxides have been synthesized based on β-pinene. Sulfides have been synthesized by the electrophilic addition reaction of thiols to the double bond of β-pinene in the presence of ZnCl2. Sulfides were oxidized to sulfoxides by such oxidizing agents as sodium periodate, meta-Chloroperoxybenzoic acid, selenium dioxide with hydrogen peroxide and sulfuryl chloride in combination with ethyl alcohol. The best result was achieved by asymmetric oxidation method using the Ti(O-i-Pr)4/(R)-mandelic acid /t-BuOOH oxidation system. Structure of synthesized compounds was ascertained by1Н and13С nuclear magnetic resonance, chromatomass spectrometry and X-ray structural analysis. Clotting activity of synthesized substances was evaluated by platelets aggregating rates and standard surface-dependent coagulation tests. Venous blood from patients with ischemic heart disease and evident changes in hemostasis system were used to determine spontaneous platelets aggregation and serum clotting activity. The induced platelets aggregation was studied on serum obtained from healthy donors.Results. The basic substance (β-pinene) did not influence the hemostasis system status in patients with ischemic heart disease. The substances synthesized on its basis have shown high anti-aggregatory activity: spontaneous velocity and aggregation coefficient reduced significantly and even reached normal values in some cases. Besides, they reduced the serum clotting activity, normalized activated partial thromboplastin time, prothrombin time international normalized ratio. However, the activity of thrombin was not influenced. The most water-soluble sulfoxide showed the most activity and almost completely inhibited spontaneous and collagen-induced and arachidonic acid-induced platelet aggregation, as well as better reduced the serum clotting activity in patients with ischemic heart disease compared to other synthesized substances.Conclusion. Taking into account low toxicity of thioterpenoids, the novel substances can be described as potentially promising drugs for medical treatment and prevention of thrombophilia and as agents for blood stabilization.