Medicinal Chemistry Research https://doi.org/10.1007/s00044-019-02371-z MEDICINAL CHEMISTRY RESEARCH ORIGINAL RESEARCH Antiplatelet activity and TNF-α release inhibition of phthalimide derivatives useful to treat sickle cell anemia Rafael C. Chelucci 1 ● Isabela J. de Oliveira 1 ● Karina P. Barbieri 1 ● Maria E. Lopes-Pires 2 ● Marisa C. Polesi 1 ● Diego E. Chiba 1 ● Iracilda Z. Carlos 1 ● Sisi Marcondes 2 ● Jean L. Dos Santos 1 ● ManChin Chung 1 Received: 22 February 2019 / Accepted: 22 May 2019 © Springer Science+Business Media, LLC, part of Springer Nature 2019 Abstract 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. Graphical Abstract Keywords Sickle cell disease ● Vaso-occlusion ● Phthalimide ● Platelet aggregation inhibition ● TNF-α inhibition. Introduction Sickle Cell Anemia (SCA) is a chronic hereditary hemato- logical disease caused by a single mutation in the HBB gene, which encodes hemoglobin subunit beta. This muta- tion causes the replacement of glutamic acid (Glu) to valine (Val) on the surface of the variant β-globin chain (βs-glo- bin) of hemoglobin S (HbS) (Ingram 1957). Interactions among β s -globin chains, at low oxygen tensions, lead to polymers formation inside HbS and alter the red blood cell * Jean L. Dos Santos jean.santos@unesp.br 1 School of Pharmaceutical Sciences, São Paulo State University (UNESP), Araraquara, São Paulo, Brazil 2 Faculty of Medical Science, State University of Campinas (Unicamp), Campinas, São Paulo, Brazil 1234567890();,: 1234567890();,: