Identification of indothiazinone as a natural antiplatelet agent

Chansik Yang, Sugyeong Kwon, Se Jong Kim, Minseon Jeong, Ji-Young Park, Dongeun Park, Soon Jun Hong, Jong Wha Jung, Chungho Kim

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Cardiovascular disease, which is caused by unregulated platelet aggregation, is one of the main causes of deaths worldwide. Many studies have focused on natural products with antiplatelet effects as a safe alternative therapy to prevent the disease. In this context, an in-house chemical library was screened to find natural products capable of inhibiting the interaction between platelet integrin αIIbβ3 and fibrinogen, which is an essential step in platelet aggregation. On the basis of the screening results, indothiazinone, an alkaloid found in microbial cultures, was identified as a potential antiplatelet agent. Specifically, indothiazinone treatment significantly inhibited the binding of fibrinogen to Chinese hamster ovary cells expressing integrin αIIbβ3. It also restricted thrombin- and adenosine diphosphate-dependent spreading of human platelets on a fibrinogen matrix. More importantly, surface plasmon resonance and molecular dynamics studies suggested that indothiazinone suppressed talin-induced activation of integrin αIIbβ3 presumably by inhibiting talin-integrin interaction. In conclusion, these results suggest that indothiazinone can be used as a lead compound for the development of antiplatelet drugs with a novel mode of action.

Original languageEnglish
JournalChemical Biology and Drug Design
DOIs
Publication statusAccepted/In press - 2017

Keywords

  • Antiplatelet drug
  • Indothiazinone
  • Integrin αIIbβ3
  • Platelet
  • Talin

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine

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