Thioterpenoids as Potential Antithrombotic Drugs: Molecular Docking, Antiaggregant, Anticoagulant and Antioxidant Activities

Biomolecules. 2022 Oct 30;12(11):1599. doi: 10.3390/biom12111599.

Abstract

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.

Keywords: P2Y12 receptor; S-containing monoterpenoids; antiaggregant and anticoagulant activities; antioxidant activity; molecular docking; oxidative hemolysis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anticoagulants / pharmacology
  • Antioxidants* / chemistry
  • Antioxidants* / pharmacology
  • Fibrinolytic Agents* / pharmacology
  • Molecular Docking Simulation
  • Sulfides / chemistry
  • Sulfones / chemistry
  • Sulfoxides / chemistry

Substances

  • Antioxidants
  • Fibrinolytic Agents
  • Anticoagulants
  • Sulfoxides
  • Sulfones
  • Sulfides

Grants and funding

The study of biological activity was conducted with the financial support of the state assignment of IB FRC Komi SC UB RAS (project no. 122040600022-1) and the Russian Science Foundation (grant N 20-64-47014). The synthetic part was conducted with the financial support of Kazan State Medical University (grant N 1/22-4).