Sulfur-Containing Monoterpenoids as Potential Antithrombotic Drugs: Research in the Molecular Mechanism of Coagulation Activity Using Pinanyl Sulfoxide as an Example

Liliya E Nikitina; Sergei V Kiselev; Valeriya A Startseva; Andrei V Bodrov; Zulfiya R Azizova; Olga T Shipina; Inna V Fedyunina; Sergei V Boichuk; Olga A Lodochnikova; Vladimir V Klochkov; Leisan F Galiullina; Aliya V Khaliullina

doi:10.3389/fphar.2018.00116

Sulfur-Containing Monoterpenoids as Potential Antithrombotic Drugs: Research in the Molecular Mechanism of Coagulation Activity Using Pinanyl Sulfoxide as an Example

Front Pharmacol. 2018 Feb 19:9:116. doi: 10.3389/fphar.2018.00116. eCollection 2018.

Affiliations

¹ Department of General and Organic Chemistry, Kazan State Medical University, Kazan, Russia.
² Medical Physics Department, Institute of Physics, Kazan Federal University, Kazan, Russia.
³ Department of Chemistry and Technology of Macromolecular Compounds, Kazan National Research Technological University, Kazan, Russia.
⁴ A.E. Arbuzov Institute of Organic and Physical Chemistry, Kazan Scientific Center, Russian Academy of Sciences, Kazan, Russia.

Abstract

In this article we present the synthesis of enantiomerically pure sulfoxide and study the influence of this compound on hemostasis. Detailed NMR studies and molecular dynamics simulations using sodium dodecyl sulfate (SDS) membrane models indicated that the bicyclic fragment of sulfoxide was embedded into the SDS micelle whereas the -SO(CH₂)₂OH fragment remained on the surface of the micelle and was in contact with the solvent. We also found that the pro-coagulative activity of sulfoxide was due to its ability to inhibit platelet activation and inhibited the catalytic activity of phospholipid surface which was involved in formation of coagulation clotting factor complexes.

Keywords: coagulation activity; molecular mechanism of coagulation activity; platelets aggregation; sulfoxides; terpenes.