| Autor: |
Nikitina LE; General and Organic Chemistry Department, Kazan State Medical University, 420012 Kazan, Russia.; Institute of Fundamental Medicine and Biology, Kazan Federal University, 420008 Kazan, Russia., Bocharov PS; G.A. Krestov Institute of Solution Chemistry of the Russian Academy of Sciences, 153045 Ivanovo, Russia., Ksenofontov AA; G.A. Krestov Institute of Solution Chemistry of the Russian Academy of Sciences, 153045 Ivanovo, Russia.; Department of Inorganic Chemistry, Ivanovo State University of Chemistry and Technology, 153045 Ivanovo, Russia., Antina EV; G.A. Krestov Institute of Solution Chemistry of the Russian Academy of Sciences, 153045 Ivanovo, Russia., Gilfanov IR; Institute of Fundamental Medicine and Biology, Kazan Federal University, 420008 Kazan, Russia.; Varnishes and Paints Coatings Department, Kazan National Research Technological University, 420015 Kazan, Russia., Pavelyev RS; Institute of Fundamental Medicine and Biology, Kazan Federal University, 420008 Kazan, Russia., Ostolopovskaya OV; General and Organic Chemistry Department, Kazan State Medical University, 420012 Kazan, Russia.; Institute of Fundamental Medicine and Biology, Kazan Federal University, 420008 Kazan, Russia., Fedyunina IV; General and Organic Chemistry Department, Kazan State Medical University, 420012 Kazan, Russia., Azizova ZR; General and Organic Chemistry Department, Kazan State Medical University, 420012 Kazan, Russia., Pestova SV; Medical Chemistry Laboratory, Institute of Chemistry, Komi Scientific Centre, Ural Branch of Russian Academy of Sciences, 167000 Syktyvkar, Russia., Izmest'ev ES; Medical Chemistry Laboratory, Institute of Chemistry, Komi Scientific Centre, Ural Branch of Russian Academy of Sciences, 167000 Syktyvkar, Russia., Rubtsova SA; Medical Chemistry Laboratory, Institute of Chemistry, Komi Scientific Centre, Ural Branch of Russian Academy of Sciences, 167000 Syktyvkar, Russia., Boichuk SV; Institute of Fundamental Medicine and Biology, Kazan Federal University, 420008 Kazan, Russia.; Department of Pathology, Kazan State Medical University, 420012 Kazan, Russia.; Department of Radiotherapy and Radiology, Russian Medical Academy of Continuous Professional Education, 125993 Moscow, Russia., Galembikova AR; Department of Pathology, Kazan State Medical University, 420012 Kazan, Russia., Smolyarchuk EA; Department of Pharmacology, Sechenov First Moscow State Medical University (Sechenov University), 125993 Moscow, Russia., Mustafin IG; Biochemistry Department, Kazan State Medical University, 420012 Kazan, Russia., Kayumov AR; Institute of Fundamental Medicine and Biology, Kazan Federal University, 420008 Kazan, Russia., Samorodov AV; Department of Pharmacology, Bashkir State Medical University, 450008 Ufa, Russia. |
| Abstrakt: |
Natural monoterpenes and their derivatives are widely considered the effective ingredients for the design and production of novel biologically active compounds. In this study, by using the molecular docking technique, we examined the effects of two series of "sulfide-sulfoxide-sulfone" thioterpenoids containing different (e.g., bornane and pinane) monoterpene skeletons on the platelet's aggregation. Our data revealed that all the synthesized compounds exhibit inhibitory activities on platelet aggregation. For example, compound 1 effectively inhibited platelet activation and demonstrated direct binding with CD61 integrin, a well-known platelet GPIIb-IIIa receptor on platelets. We further examined the antiaggregant activity of the most active compound, 1 , in vivo and compared its activity with that of acetylsalicylic acid and an oral GPIIb-IIIa blocker, orbofiban. We found that compound 1 demonstrates antiaggregant activity in rats when administered per os and its activity was comparable with that of acetylsalicylic acid and orbofiban. Moreover, similarly, tirofiban, a well-known GPIIb-IIIa blocker, compound 1 , effectively decreased the expression of P-selectin to the values similar to those of the intact platelets. Collectively, here, we show, for the first time, the potent antiaggregant activity of compound 1 both in vitro and in vivo due to its ability to bind with the GPIIb-IIIa receptor on platelets. |
