Linking triphenylphosphonium cation to a bicyclic hydroquinone improves their antiplatelet effect via the regulation of mitochondrial function
Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved..
Platelets are the critical target for preventing and treating pathological thrombus formation. However, despite current antiplatelet therapy, cardiovascular mortality remains high, and cardiovascular events continue in prescribed patients. In this study, first results were obtained with ortho-carbonyl hydroquinones as antiplatelet agents; we found that linking triphenylphosphonium cation to a bicyclic ortho-carbonyl hydroquinone moiety by a short alkyl chain significantly improved their antiplatelet effect by affecting the mitochondrial functioning. The mechanism of action involves uncoupling OXPHOS, which leads to an increase in mitochondrial ROS production and a decrease in the mitochondrial membrane potential and OCR. This alteration disrupts the energy production by mitochondrial function necessary for the platelet activation process. These effects are responsive to the complete structure of the compounds and not to isolated parts of the compounds tested. The results obtained in this research can be used as the basis for developing new antiplatelet agents that target mitochondria.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:72 |
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| Enthalten in: |
Redox biology - 72(2024) vom: 06. Mai, Seite 103142 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Méndez, Diego [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 05.05.2024 Date Revised 05.05.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.redox.2024.103142 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 520 | |a Platelets are the critical target for preventing and treating pathological thrombus formation. However, despite current antiplatelet therapy, cardiovascular mortality remains high, and cardiovascular events continue in prescribed patients. In this study, first results were obtained with ortho-carbonyl hydroquinones as antiplatelet agents; we found that linking triphenylphosphonium cation to a bicyclic ortho-carbonyl hydroquinone moiety by a short alkyl chain significantly improved their antiplatelet effect by affecting the mitochondrial functioning. The mechanism of action involves uncoupling OXPHOS, which leads to an increase in mitochondrial ROS production and a decrease in the mitochondrial membrane potential and OCR. This alteration disrupts the energy production by mitochondrial function necessary for the platelet activation process. These effects are responsive to the complete structure of the compounds and not to isolated parts of the compounds tested. The results obtained in this research can be used as the basis for developing new antiplatelet agents that target mitochondria | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Antiplatelet | |
| 650 | 4 | |a Hydroquinone derivatives: triphenylphosphonium cation | |
| 650 | 4 | |a Mitochondria | |
| 650 | 4 | |a Uncoupler | |
| 650 | 7 | |a Platelet Aggregation Inhibitors |2 NLM | |
| 650 | 7 | |a Hydroquinones |2 NLM | |
| 650 | 7 | |a Organophosphorus Compounds |2 NLM | |
| 650 | 7 | |a Reactive Oxygen Species |2 NLM | |
| 650 | 7 | |a triphenylphosphonium |2 NLM | |
| 700 | 1 | |a Tellería, Francisca |e verfasserin |4 aut | |
| 700 | 1 | |a Monroy-Cárdenas, Matías |e verfasserin |4 aut | |
| 700 | 1 | |a Montecino-Garrido, Héctor |e verfasserin |4 aut | |
| 700 | 1 | |a Mansilla, Santiago |e verfasserin |4 aut | |
| 700 | 1 | |a Castro, Laura |e verfasserin |4 aut | |
| 700 | 1 | |a Trostchansky, Andrés |e verfasserin |4 aut | |
| 700 | 1 | |a Muñoz-Córdova, Felipe |e verfasserin |4 aut | |
| 700 | 1 | |a Zickermann, Volker |e verfasserin |4 aut | |
| 700 | 1 | |a Schiller, Jonathan |e verfasserin |4 aut | |
| 700 | 1 | |a Alfaro, Sergio |e verfasserin |4 aut | |
| 700 | 1 | |a Caballero, Julio |e verfasserin |4 aut | |
| 700 | 1 | |a Araya-Maturana, Ramiro |e verfasserin |4 aut | |
| 700 | 1 | |a Fuentes, Eduardo |e verfasserin |4 aut | |
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