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

Autor(es)

Chelucci, Rafael C. ^[1] ; de Oliveira, Isabela J. ^[1] ; Barbieri, Karina P. ^[1] ; Lopes-Pires, Maria E. ^[2] ; Polesi, Marisa C. ^[1] ; Chiba, Diego E. ^[1] ; Carlos, Iracilda Z. ^[1] ; Marcondes, Sisi ^[2] ; Dos Santos, Jean L. ^[1] ; Chung, ManChin ^[1]

Afiliação do(s) autor(es)

^[1] Sao Paulo State Univ UNESP, Sch Pharmaceut Sci, Araraquara, SP - Brazil

^[2] State Univ Campinas UNICAMP, Fac Med Sci, Campinas, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: MEDICINAL CHEMISTRY RESEARCH; v. 28, n. 8, p. 1264-1271, AUG 2019.
• Citações Web of Science: 0

Resumo

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-) 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- 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. {[}GRAPHICS] . (AU)

• Processo FAPESP: 15/19531-1 - Inibição de histona deacetilase (HDAC-1 e HDAC-2) como alvos para indução de Hemoglobina Fetal na Anemia Falciforme
• Beneficiário: Jean Leandro dos Santos
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 13/23461-3 - Planejamento, síntese e avaliação farmacológica de híbridos com potencial atividade no tratamento da Doença de Alzheimer
• Beneficiário: Rafael Consolin Chelucci
• Modalidade de apoio: Bolsas no Brasil - Doutorado