Designing Natural Product Hybrids Bearing Triple Antiplatelet Profile and Evaluating Their Human Plasma Stability

  • Antonis Tsiailanis
  • Maria Tsoumani
  • Evgenios K. Stylos
  • Maria V. Chatziathanasiadou
  • Tahsin F. Kellici
  • Thomas Mavromoustakos
  • Alexandros D. Tselepis
  • Andreas G. Tzakos
Part of the Methods in Molecular Biology book series (MIMB, volume 1824)


Cardiovascular diseases (CVDs) are becoming major contributors to the burden of disease due to genetic and environmental factors. Despite current standard oral care, cardiovascular risk remains relatively high. A triple antiplatelet therapy with a cyclooxygenase-1 (COX-1) inhibitor, a P2Y12 receptor antagonist, and a protease-activated receptor-1 (PAR-1) antagonist has been established in the secondary prevention of atherothrombosis in patients with acute myocardial infraction and in those with peripheral artery disease. However, due to the combinatorial use of three different drugs, patients receiving this triple therapy are exposed to enhanced risk of bleeding. Conforming to polypharmacology principles, the discovery of a single compound that can simultaneously block the three platelet activation pathways (PAR-1, P2Y12, and COX-1) is of importance. Natural products have served as an inexhaustible source of bioactive compounds presenting a diverse pharmaceutical profile, including anti-inflammatory, antioxidant, anticancer, and antithrombotic activity. Indeed, principal component analysis indicated that natural products have the potential to inhibit the three aforementioned pathways, though existed reports refer to single inhibition mechanism on specific receptor(s) implicated in platelet activation. We thus set out to explore possibilities that take advantage of this potential of natural products and shape the basis to produce novel compounds that could simultaneously target PAR-1, P2Y12, and COX-1 platelet activation pathways. Polyunsaturated fatty acids (PUFAs) have multiple effects leading to improvements in blood pressure and cardiac function and arterial compliance. A promising approach to achieve the desirable goal is the bioconjugation of natural products with PUFAs. Herein, we describe the principles that should be followed to develop molecular hybrids bearing triple antiplatelet activity profile.

Key words

Triple antiplatelet activity Flavonoids Liquid chromatography Plasma stability LC-MS Polyunsaturated fatty acids 


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Antonis Tsiailanis
    • 1
  • Maria Tsoumani
    • 2
  • Evgenios K. Stylos
    • 1
    • 3
  • Maria V. Chatziathanasiadou
    • 1
  • Tahsin F. Kellici
    • 4
  • Thomas Mavromoustakos
    • 4
  • Alexandros D. Tselepis
    • 2
  • Andreas G. Tzakos
    • 1
  1. 1.Section of Organic Chemistry and Biochemistry, Department of ChemistryUniversity of IoanninaIoanninaGreece
  2. 2.Atherothrombosis Research Centre/Laboratory of Biochemistry, Department of ChemistryUniversity of IoanninaIoanninaGreece
  3. 3.Biotechnology Laboratory, Department of Biological Applications and TechnologyUniversity of IoanninaIoanninaGreece
  4. 4.Division of Organic Chemistry, Department of ChemistryNational and Kapodistrian University of Athens, Panepistimiopolis ZografouAthensGreece

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