Linking triphenylphosphonium cation to a bicyclic hydroquinone improves their antiplatelet effect via the regulation of mitochondrial function.
Redox Biol
; 72: 103142, 2024 Jun.
Article
in En
| MEDLINE
| ID: mdl-38581860
ABSTRACT
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Organophosphorus Compounds
/
Blood Platelets
/
Platelet Aggregation Inhibitors
/
Reactive Oxygen Species
/
Membrane Potential, Mitochondrial
/
Hydroquinones
/
Mitochondria
Limits:
Humans
Language:
En
Journal:
Redox Biol
Year:
2024
Document type:
Article
Affiliation country: