Identification of indothiazinone as a natural antiplatelet agent |
| |
| Authors: | Se‐Jong Kim Minseon Jeong Ji‐Young Park Dongeun Park Soon Jun Hong Jong‐Wha Jung Chungho Kim |
| |
| Affiliation: | 1. Department of Life Sciences, Korea University, Seoul, Korea;2. College of Pharmacy, Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu, Korea;3. Department of Clinical Pharmacology and Toxicology, Korea University Anam Hospital, Seoul, Korea;4. School of Biological Sciences, Seoul National University, Seoul, Korea;5. Department of Cardiology, Cardiovascular Center, Korea University Anam Hospital, Seoul, Korea |
| |
| 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. |
| |
| Keywords: | antiplatelet drug indothiazinone integrin α IIbβ 3 platelet talin |
|
|
