Thioterpenoids as Potential Antithrombotic Drugs: Molecular Docking, Antiaggregant, Anticoagulant and Antioxidant Activities
Alexander A. Ksenofontov,
Pavel S. Bocharov,
Elena V. Antina,
Oksana G. Shevchenko,
Aleksandr V. Samorodov,
Ilmir R. Gilfanov,
Roman S. Pavelyev,
Olga V. Ostolopovskaya,
Valeriya A. Startseva,
Inna V. Fedyunina,
Zulfiya R. Azizova,
Salavat I. Gaysin,
Svetlana V. Pestova,
Evgeniy S. Izmest’ev,
Svetlana A. Rubtsova,
Mohammed A. Khelkhal,
Liliya E. Nikitina
Affiliations
Alexander A. Ksenofontov
G.A. Krestov Institute of Solution Chemistry of the Russian Academy of Sciences, 1 Akademicheskaya Street, 153045 Ivanovo, Russia
Pavel S. Bocharov
G.A. Krestov Institute of Solution Chemistry of the Russian Academy of Sciences, 1 Akademicheskaya Street, 153045 Ivanovo, Russia
Elena V. Antina
G.A. Krestov Institute of Solution Chemistry of the Russian Academy of Sciences, 1 Akademicheskaya Street, 153045 Ivanovo, Russia
Oksana G. Shevchenko
Center of Collective Usage «Molecular Biology», Institute of Biology, Komi Science Centre, Ural Branch of Russian Academy of Sciences, 28 Kommunisticheskaya Street, 167982 Syktyvkar, Russia
Aleksandr V. Samorodov
Biologically Active Terpenoids Laboratory, Institute of Fundamental Medicine and Biology, Kazan Federal University, 18 Kremlevskaya Street, 420008 Kazan, Russia
Ilmir R. Gilfanov
Biologically Active Terpenoids Laboratory, Institute of Fundamental Medicine and Biology, Kazan Federal University, 18 Kremlevskaya Street, 420008 Kazan, Russia
Roman S. Pavelyev
Biologically Active Terpenoids Laboratory, Institute of Fundamental Medicine and Biology, Kazan Federal University, 18 Kremlevskaya Street, 420008 Kazan, Russia
Olga V. Ostolopovskaya
Biologically Active Terpenoids Laboratory, Institute of Fundamental Medicine and Biology, Kazan Federal University, 18 Kremlevskaya Street, 420008 Kazan, Russia
Valeriya A. Startseva
Biologically Active Terpenoids Laboratory, Institute of Fundamental Medicine and Biology, Kazan Federal University, 18 Kremlevskaya Street, 420008 Kazan, Russia
Inna V. Fedyunina
Biologically Active Terpenoids Laboratory, Institute of Fundamental Medicine and Biology, Kazan Federal University, 18 Kremlevskaya Street, 420008 Kazan, Russia
Zulfiya R. Azizova
Biologically Active Terpenoids Laboratory, Institute of Fundamental Medicine and Biology, Kazan Federal University, 18 Kremlevskaya Street, 420008 Kazan, Russia
Salavat I. Gaysin
General and Organic Chemistry Department, Kazan State Medical University, 49 Butlerova Street, 420012 Kazan, Russia
Svetlana V. Pestova
Medical Chemistry Laboratory, Institute of Chemistry, Komi Scientific Centre, Ural Branch of Russian Academy of Sciences, 48 Pervomaiskaya Street, 167000 Syktyvkar, Russia
Evgeniy S. Izmest’ev
Medical Chemistry Laboratory, Institute of Chemistry, Komi Scientific Centre, Ural Branch of Russian Academy of Sciences, 48 Pervomaiskaya Street, 167000 Syktyvkar, Russia
Svetlana A. Rubtsova
Medical Chemistry Laboratory, Institute of Chemistry, Komi Scientific Centre, Ural Branch of Russian Academy of Sciences, 48 Pervomaiskaya Street, 167000 Syktyvkar, Russia
Mohammed A. Khelkhal
Biologically Active Terpenoids Laboratory, Institute of Fundamental Medicine and Biology, Kazan Federal University, 18 Kremlevskaya Street, 420008 Kazan, Russia
Liliya E. Nikitina
Biologically Active Terpenoids Laboratory, Institute of Fundamental Medicine and Biology, Kazan Federal University, 18 Kremlevskaya Street, 420008 Kazan, Russia
Natural monoterpenes and their derivatives are widely considered as effective ingredients for the design and production of new biologically active compounds with high antioxidant, antimicrobial and anti-protozoa properties. In this study, we synthesized two series of thiotherpenoids “sulfide-sulfoxide-sulfone”, with different bicyclic monoterpene skeleton (bornane and pinane) structures. The effect of the obtained compounds on platelet aggregation was investigated by using the molecular docking technique. The obtained data revealed that all the synthesized compounds may act as potential inhibitors of platelet aggregation. Moreover, the studied sulfides have shown high antioxidant activity as revealed by lipid peroxidation (LPO) process inhibition in a non-cellular substrate containing animal lipids. The sulfides were able to inhibit erythrocyte oxidative hemolysis, to reduce the accumulation of secondary LPO products in cells and to prevent the oxidation of native oxyhemoglobin. Additionally, the corresponding sulfones and sulfoxides exhibited insignificant antioxidant activity. However, the sulfides were found to exhibit significant antiaggregant and anticoagulant effects. These findings suggest as well that the sulfides could serve as a leader compound for future research and possible practical applications.
