Design and synthesis of new drug candidates useful for treating symptoms of sickle cell anemia

• Grant number: 11/06050-4
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): August 01, 2011
• Effective date (End): July 31, 2012
• Field of knowledge: Health Sciences - Pharmacy - Medicines Analysis and Control
• Principal Investigator: Jean Leandro dos Santos
• Grantee: Renata Monteiro Mota
• Host Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil

Abstract

Sickle cell anemia (SCA) is a chronic hemolytic anemia characterized by the presence of red blood cells, when deprived of oxygen, take the form of a sickle. The vaso-occlusive process is the main characteristic of this disease and it seems to be related among other factors to the increase of adhesion molecules. In this context, the chronic inflammatory nature of the disease can be considered as an important target for therapeutic intervention, as it is known that some pro-inflammatory cytokines such as tumor necrosis factor alpha (TNF-a) increases the expression of those adhesion molecules. It has been reported that patients with SCD have increased circulating levels of TNF-a.Nowadays, the only drug available for treatment is hydroxyurea (HU), whose beneficial effects are related in part to the ability of this biotransformation in vivo 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 line of research aimed at the design and synthesis of new prototypes drug candidates to treat the symptoms of sickle cell anemia will be a series of compounds synthesized hybrids (3a-d) according to the structural planning (Scheme 1 ). The strategy for the donation of nitric oxide associated with inhibition of TNF-a represents a new therapeutic approach to treat the symptoms of sickle cell anemia, and showed promising according to the data previously obtained in our laboratory.