Evaluation of novel factor Xa inhibitors from Oxya chinensis sinuosa with anti-platelet aggregation activity

Abstract The edible grasshopper Oxya chinensis sinuosa is consumed worldwide for its various medicinal effects. The purpose of this study was to investigate potential bioactive antithrombotic and antiplatelet compounds from O. chinensis sinuosa. Five N-acetyldopamine dimers (1–5) were isolated from...

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Autores principales:	Wonhwa Lee, HeeSeung Lee, Mi-Ae Kim, Joonhyeok Choi, Kyung-Min Kim, Jae Sam Hwang, MinKyun Na, Jong-Sup Bae
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/6b32a3d2d26d4e3692a0d3e3a83a4cb8
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spelling	oai:doaj.org-article:6b32a3d2d26d4e3692a0d3e3a83a4cb82021-12-02T16:07:48ZEvaluation of novel factor Xa inhibitors from Oxya chinensis sinuosa with anti-platelet aggregation activity10.1038/s41598-017-08330-12045-2322https://doaj.org/article/6b32a3d2d26d4e3692a0d3e3a83a4cb82017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-08330-1https://doaj.org/toc/2045-2322Abstract The edible grasshopper Oxya chinensis sinuosa is consumed worldwide for its various medicinal effects. The purpose of this study was to investigate potential bioactive antithrombotic and antiplatelet compounds from O. chinensis sinuosa. Five N-acetyldopamine dimers (1–5) were isolated from O. chinensis sinuosa and compounds 1 and 2 were identified as new chemicals with chiral centers at H-2 and H-3 of the benzo-1,4-dioxane structure. Compounds 1–4 were found to have both FXa and platelet aggregation inhibitory activities. These compounds inhibited the catalytic activity of FXa toward its synthetic substrate, S-2222, by noncompetitive inhibition, and inhibited platelet aggregation induced by ADP and U46619. Furthermore, compounds 1–4 showed enhanced antithrombotic effects, which were assessed using in vivo models of pulmonary embolism and arterial thrombosis. The isolated compounds also showed anticoagulant effects in mice. However, compounds 1–4 did not prolong bleeding time in mice, as shown by tail clipping. N-Acetyldopamine dimers, including two new stereoisomers 1 and 2, are novel antithrombotic compounds showing both FXa inhibition and antiplatelet aggregation activity with a low bleeding risk. Collectively, these results suggest that compounds 1–4 could serve as candidates and provide scaffolds for development of new antithrombotic drugs.Wonhwa LeeHeeSeung LeeMi-Ae KimJoonhyeok ChoiKyung-Min KimJae Sam HwangMinKyun NaJong-Sup BaeNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-13 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Wonhwa Lee HeeSeung Lee Mi-Ae Kim Joonhyeok Choi Kyung-Min Kim Jae Sam Hwang MinKyun Na Jong-Sup Bae Evaluation of novel factor Xa inhibitors from Oxya chinensis sinuosa with anti-platelet aggregation activity
description	Abstract The edible grasshopper Oxya chinensis sinuosa is consumed worldwide for its various medicinal effects. The purpose of this study was to investigate potential bioactive antithrombotic and antiplatelet compounds from O. chinensis sinuosa. Five N-acetyldopamine dimers (1–5) were isolated from O. chinensis sinuosa and compounds 1 and 2 were identified as new chemicals with chiral centers at H-2 and H-3 of the benzo-1,4-dioxane structure. Compounds 1–4 were found to have both FXa and platelet aggregation inhibitory activities. These compounds inhibited the catalytic activity of FXa toward its synthetic substrate, S-2222, by noncompetitive inhibition, and inhibited platelet aggregation induced by ADP and U46619. Furthermore, compounds 1–4 showed enhanced antithrombotic effects, which were assessed using in vivo models of pulmonary embolism and arterial thrombosis. The isolated compounds also showed anticoagulant effects in mice. However, compounds 1–4 did not prolong bleeding time in mice, as shown by tail clipping. N-Acetyldopamine dimers, including two new stereoisomers 1 and 2, are novel antithrombotic compounds showing both FXa inhibition and antiplatelet aggregation activity with a low bleeding risk. Collectively, these results suggest that compounds 1–4 could serve as candidates and provide scaffolds for development of new antithrombotic drugs.
format	article
author	Wonhwa Lee HeeSeung Lee Mi-Ae Kim Joonhyeok Choi Kyung-Min Kim Jae Sam Hwang MinKyun Na Jong-Sup Bae
author_facet	Wonhwa Lee HeeSeung Lee Mi-Ae Kim Joonhyeok Choi Kyung-Min Kim Jae Sam Hwang MinKyun Na Jong-Sup Bae
author_sort	Wonhwa Lee
title	Evaluation of novel factor Xa inhibitors from Oxya chinensis sinuosa with anti-platelet aggregation activity
title_short	Evaluation of novel factor Xa inhibitors from Oxya chinensis sinuosa with anti-platelet aggregation activity
title_full	Evaluation of novel factor Xa inhibitors from Oxya chinensis sinuosa with anti-platelet aggregation activity
title_fullStr	Evaluation of novel factor Xa inhibitors from Oxya chinensis sinuosa with anti-platelet aggregation activity
title_full_unstemmed	Evaluation of novel factor Xa inhibitors from Oxya chinensis sinuosa with anti-platelet aggregation activity
title_sort	evaluation of novel factor xa inhibitors from oxya chinensis sinuosa with anti-platelet aggregation activity
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/6b32a3d2d26d4e3692a0d3e3a83a4cb8
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Evaluation of novel factor Xa inhibitors from Oxya chinensis sinuosa with anti-platelet aggregation activity

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