Antiplatelet activity and TNF-α release inhibition of phthalimide derivatives useful to treat sickle cell anemia

• Published in: Medicinal chemistry research 2019-08, Vol.28 (8), p.1264-1271
• Main Authors: Chelucci, Rafael C., de Oliveira, Isabela J., Barbieri, Karina P., Lopes-Pires, Maria E., Polesi, Marisa C., Chiba, Diego E., Carlos, Iracilda Z., Marcondes, Sisi, Dos Santos, Jean L., Chung, ManChin
• Format: Article
• Language: English
• Subjects: Acetylsalicylic acid; Adenosine; Adenosine diphosphate; Anemia; Biochemistry; Biomedical and Life Sciences; Biomedicine; Bleeding; Cell Biology; Collagen; Derivatives; Hematological diseases; Lead compounds; Occlusion; Original Research; Pharmacology/Toxicology; Phthalimide; Platelet aggregation; Sickle cell anemia; Sickle cell disease; Tumor necrosis factor-TNF; Tumor necrosis factor-α
• ISSN: 1054-2523; 1554-8120
• DOI: 10.1007/s00044-019-02371-z

Sickle Cell Anemia (SCA) is one of the most prevalent hereditary hematological diseases worldwide. The disease is characterized by chronic inflammation, hypercoagulable state, and pro-thrombotic profile, which lead the vaso-occlusive process. In this work, we described the antiplatelet activity and the ability to reduce tumor necrosis factor-alpha (TNF-α) levels of phthalimide derivatives. All compounds inhibited platelet aggregation induced by collagen and adenosine diphosphate, at levels ranging from 26.0 to 74.2% and 30.7 to 79.6%, respectively. The compounds exhibited reduced bleeding time compared to acetylsalicylic acid (ASA). Moreover, compounds 4c and 10c inhibited TNF-α levels at 73.5% and 65.0%, respectively. These findings suggest that phthalimide derivatives 4c and 10c are promising lead compounds useful to prevent vaso-occlusion and inflammation associated with the sickle cell anemia.