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BioMed Research International
Volume 2016 (2016), Article ID 8587164, 8 pages
http://dx.doi.org/10.1155/2016/8587164
Research Article

A Naphthalenic Derivative ND-1 Inhibits Thrombus Formation by Interfering the Binding of Fibrinogen to Integrin αIIbβ3

1School of Life Science & Technology, China Pharmaceutical University, 24 Tong Jia Street, Nanjing 210009, China
2School of Pharmacy, China Pharmaceutical University, 24 Tong Jia Street, Nanjing 210009, China
3Department of Cancer Biology, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA
4State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tong Jia Street, Nanjing 210009, China

Received 1 September 2016; Revised 28 October 2016; Accepted 10 November 2016

Academic Editor: Jane Hanrahan

Copyright © 2016 Xue Ding et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Integrin αIIbβ3 plays a crucial role in the process of platelet aggregation. Three integrin αIIbβ3 antagonists (abciximab, eptifibatide, and tirofiban) have been approved by FDA for clinical use. Unfortunately, they all showed severe side effects such as thrombocytopenia and bleeding risk. Thus, researches on the development of more effective and safer antiplatelet agents are needed. In this manuscript we reported a novel naphthalenic derivative compound ND-1 with potent antithrombotic effect and lower bleeding risk. ND-1 inhibited ADP-, collagen-, thrombin-, and U46619-induced platelet aggregation with IC50 values of 1.29, 14.46, 12.84, and 40.24 μM, respectively. Mechanism studies indicated that ND-1 inhibited the binding of fibrinogen to integrin αIIbβ3 in a dose-dependent manner with an IC50 value of 3.12 μM. ND-1 inhibited P-selectin expression induced by ADP, collagen, thrombin, and U46619 on the surface of platelets. Additionally, this compound reduced platelets spreading to the immobilized fibrinogen. In vivo, ND-1 potently decreased thrombus formation in an arteriovenous shunt thrombosis model in rats and slightly prolonged bleeding time in a tail cutting model in mice. Taken together, our results reveal that ND-1 is a novel antagonist of αIIbβ3 with strong antithrombotic effect and lower bleeding risk.