Clotting activity of camphene derivatives

Abstract

Aim. To study of the influence of new synthetized sulfur-containing derivatives of camphene on the thrombocytes aggregating ability and clotting activity of human blood plasma in vitro. Methods. Sulfides and sulphones of camphene were synthesized by thiols electrophilic addition reaction. The structures of the synthetized compounds were clarified by using of 1H and 13C nuclear magnetic resonance, chromato-mass spectrometry and X-ray analysis. Clotting activity of the synthetized compounds was assessed by studying the spontaneous platelet aggregation and plasma coagulating activity of the venous blood of patients with ischemic heart disease. The induced platelets aggregation was studied on plasma obtained from healthy donors. Results. The synthetized compounds demonstrated anti-aggregating and anti-coagulating activity: they inhibited spontaneous and induced thrombocyte aggregation as well as reduced coagulating ability of human plasma. Both camphene sulphone and mainly camphene sulfide (in contrast with acetylsalicylic acid and clopidogrel) totally inhibited thrombocytes aggregation induced by adrenaline, adenosine diphosphate, collagen and arachidonic acid, and decreased the influence of ristocetin. Anticoagulant activity of the synthetized substances is associated to their potential to inhibit thrombocyte activation and to reduce the catalyst activity of phospholipid surface participating in coagulating complexes and clotting factors formation. Conclusion. Low toxicity of terpenoids together with discovered anticoagulant activity of sulfur-containing derivatives of camphene revealing the promising potential of these drugs for further development of novel medical treatments for treating and prevention of different types of thrombophilia.