Design, synthesis, and in vitro antiplatelet aggregation activities of taiwanin C

Abstract

Total synthesis of taiwanin C was realised efficiently in a global yield of 52%. Taiwanin C in aggregation assays inhibited platelet aggregation in a concentration-dependent manner with an IC₅₀ of 0.46 μM after exposure of human platelet to AA. Similarly, to AA, taiwanin C inhibited significantly TRAP-6-induced platelet aggregation with IC₅₀ of 0.56 μM. Molecular docking studies were carried out using the molecular target the COX-1, COX-2 and PAR-1 proteins. These studies suggest that taiwanin inhibits COX-1 more strongly than COX-2. Taiwanin C showed better antiplatelet action in the presence of TRAP-6 than indomethacin and molecular docking studies suggest different mechanisms of action for the two compounds on PAR-1. These results demonstrate that taiwanin C acts very efficiently in two different signaling pathways of platelet aggregation. Although preliminary, these results indicate that taiwanin C has potential for further studies on its use for the development of new antiplatelet.

Graphical Abstract

Keywords:

• PAR-1
• COX-1
• human platelet
• arylnaphthalene lignan

Disclosure statement

No potential conflict of interest was reported by the authors

Additional information

Funding

This study was financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior – Brasil (CAPES) Finance Code 001. R.L.T.P. and R.P.O. Thank grants 2018/00544-4 São Paulo Research Foundation (FAPESP) for the financial support. R.L.T.P. also thanks the National Council for Scientific and Technological Development (CNPq, grant 308622/2017-0 and 313660/2020-4) for the financial support.