Antiplatelet activity and toxicity profile of novel phosphonium salts derived from Michael reaction.
Eur J Pharm Sci
; 194: 106692, 2024 Mar 01.
Article
en En
| MEDLINE
| ID: mdl-38181870
ABSTRACT
In this work, five novel phosphonium salts derived from the Michael reaction were screened for their antiplatelet activity. Our findings revealed that compounds 2a, 2b, 2c, and 2d significantly inhibit platelet aggregation triggered by ADP or collagen (P < 0.001). Notably, compound 2c inhibited the arachidonic acid pathway (P < 0.001). Moreover, the selected compounds reduce CD62-P expression and inhibit GPIIb/IIIa activation. The interactions of the active compounds with their targets, ADP and collagen receptors, P2Y12 and GPVI respectively were investigated in silico using molecular docking studies. The results revealed a strong affinity of the active compounds for P2Y12 and GPVI. Additionally, cytotoxicity assays on platelets, erythrocytes, and human embryonic kidney HEK293 cells showed that compounds 2a, 2c and 2d were non-toxic even at high concentrations. In summary, our study shows that phosphonium salts can have strong antiplatelet power and suggests that compounds 2a, 2c and 2d could be promising antiplatelet agents for the management of cardiovascular diseases.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Sales (Química)
/
Inhibidores de Agregación Plaquetaria
Límite:
Humans
Idioma:
En
Revista:
Eur J Pharm Sci
/
Eur. j. pharm. sci
/
European journal of pharmaceutical sciences
Asunto de la revista:
FARMACIA
/
FARMACOLOGIA
/
QUIMICA
Año:
2024
Tipo del documento:
Article
País de afiliación:
Túnez