Future medicinal chemistry · 2026
Antiplatelet activity and cytotoxicity assessment of Morita-Baylis-Hillman-based alcohol, acetate, and phosphonate derivatives.
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Hadjkacem Basma, Haffouz Asma, Elleuch Haitham, Bedoui Ameni, Hadiji Nadia, ElhadjAhmed Leila, Jomaa Malek, Ben Amor Ikram, Jerbi Amira, Gargouri Jalel, Rezgui Farhat, Gargouri Ali
Аннотация
AIMS: Antiplatelet drugs are commonly used to prevent cardiovascular diseases (CVD). However, they are associated with side effects, highlighting the need for safer and more effective alternatives. The purpose of the present work was to evaluate the antiplatelet potential of a series of Morita-Baylis-Hillman (MBH) adducts and to test their safety.
MATERIALS & METHODS: The antiplatelet activity was assessed using microplate aggregometry and confirmed by the turbidimetric method, utilizing platelet-rich plasma (PRP) from healthy volunteers. Next, we examined the effect of the selected compounds on platelet secretion, GPIIb/IIIa complex activation, and blood coagulation. The safety of the antiplatelet agents was evaluated by testing their cytotoxicity on platelets and erythrocytes.
RESULTS: Among the tested compounds, Al4, OAc1, OAc2, OAc3, R12, R22, R32, and R52 demonstrated potent inhibition of Adenosine 5'-diphosphate (ADP)-induced platelet aggregation, with IC50 values ranging from 0.042 to 0.4 mM. The selected compounds also inhibited platelet aggregation induced by arachidonic acid (AA) and collagen. Notably, they significantly inhibited P-selectin expression and GPIIb/IIIa activation, without affecting coagulation parameters. Toxicological evaluation showed that these compounds did not induce hemolytic or cytotoxic effects on human erythrocytes or platelets.
CONCLUSION: Collectively, these results identify MBH adducts as promising scaffolds for the development of novel selective antiplatelet agents.
MATERIALS & METHODS: The antiplatelet activity was assessed using microplate aggregometry and confirmed by the turbidimetric method, utilizing platelet-rich plasma (PRP) from healthy volunteers. Next, we examined the effect of the selected compounds on platelet secretion, GPIIb/IIIa complex activation, and blood coagulation. The safety of the antiplatelet agents was evaluated by testing their cytotoxicity on platelets and erythrocytes.
RESULTS: Among the tested compounds, Al4, OAc1, OAc2, OAc3, R12, R22, R32, and R52 demonstrated potent inhibition of Adenosine 5'-diphosphate (ADP)-induced platelet aggregation, with IC50 values ranging from 0.042 to 0.4 mM. The selected compounds also inhibited platelet aggregation induced by arachidonic acid (AA) and collagen. Notably, they significantly inhibited P-selectin expression and GPIIb/IIIa activation, without affecting coagulation parameters. Toxicological evaluation showed that these compounds did not induce hemolytic or cytotoxic effects on human erythrocytes or platelets.
CONCLUSION: Collectively, these results identify MBH adducts as promising scaffolds for the development of novel selective antiplatelet agents.