A novel naphthalimide derivative reduces platelet activation and thrombus formation via suppressing GPVI

Tzenge Lien Shih, Kuan Hung Lin, Ray Jade Chen, Ting Yu Chen, Wei Ting Kao, Jen Wei Liu, Hsueh Hsiao Wang, Hsien Yu Peng, Yu Yo Sun, Wan Jung Lu*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

5 Scopus citations


Naphthalimide derivatives have multiple biological activities, including antitumour and anti-inflammatory activities. We previously synthesized several naphthalimide derivatives; of them, compound 5 was found to exert the strongest inhibitory effect on human DNA topoisomerase II activity. However, the effects of naphthalimide derivatives on platelet activation have not yet been investigated. Therefore, the mechanism underlying the antiplatelet activity of compound 5 was determined in this study. The data revealed that compound 5 (5–10 μM) inhibited collagen- and convulxin- but not thrombin- or U46619-mediated platelet aggregation, suggesting that compound 5 is more sensitive to the inhibition of glycoprotein VI (GPVI) signalling. Indeed, compound 5 could inhibit the phosphorylation of signalling molecules downstream of GPVI, followed by the inhibition of calcium mobilization, granule release and GPIIb/IIIa activation. Moreover, compound 5 prevented pulmonary embolism and prolonged the occlusion time, but tended to prolong the bleeding time, indicating that it can prevent thrombus formation but may increase bleeding risk. This study is the first to demonstrate that the naphthalimide derivative compound 5 exerts antiplatelet and antithrombotic effects. Future studies should modify compound 5 to synthesize more potent and efficient antiplatelet agents while minimizing bleeding risk, which may offer a therapeutic potential for cardiovascular diseases.

Original languageEnglish
Pages (from-to)9434-9446
Number of pages13
JournalJournal of Cellular and Molecular Medicine
Issue number19
StatePublished - 10 2021
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2021 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.


  • antiplatelet activity
  • bleeding risk
  • collagen
  • naphthalimide derivatives
  • platelet activation
  • thrombus formation


Dive into the research topics of 'A novel naphthalimide derivative reduces platelet activation and thrombus formation via suppressing GPVI'. Together they form a unique fingerprint.

Cite this