Sickle cell disease (SCD) is an hereditary chronic hemolytic anemia characterized by the presence of red blood cells that when deprived of oxygen, take the form of sickle. It has been reported that patients with SCD have increased circulating levels of proinflammatory cytokines such as tumor necrosis factor alpha (TNF-alpha). Hydroxyurea (HU) is the most widely drug used for treatment and its beneficial effects are related in part to the ability of HU after in vivo biotransformation converted to nitric oxide (NO). Among the beneficial effects of NO include: vasodilation, inhibition of platelet aggregation and induction of gamma globin gene expression - constituent of fetal hemoglobin.In this context, in continuity with a research aimed at planned, synthesized and evaluated through pharmacological assays new drug candidates to treat the symptoms of sickle cell disease will be synthesized, for optimization purposes, a series of hybrid compounds (3a-d) according to the structural planning (Figure 1). The strategy of NO donation associated with TNF-alpha inhibition represents a new therapeutic approach to treat the symptoms of sickle cell disease, and showed promise in accordance with previously data obtained in our laboratory.
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