Hybrids of thalidomide + furoxan derivatives: evaluation of anti-inflammatory properties and induction of gamma globin in vitro

• Grant number: 15/16188-4
• Support Opportunities: Scholarships in Brazil - Master
• Effective date (Start): December 01, 2015
• Effective date (End): July 31, 2017
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Fernando Ferreira Costa
• Grantee: Cristiane Maria de Souza
• Host Institution: Centro de Hematologia e Hemoterapia (HEMOCENTRO). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated research grant: 14/00984-3 - Red blood cell disorders: pathophysiology and new therapeutic approaches, AP.TEM

Abstract

Sickle cell anemia (SCA) occurs due to molecular alterations in the beta globin gene. The key event in the pathogenesis of sickle cell anemia is deoxy-HbS polymerization. Deoxy-HbS polymerization depends on some factors such as: oxygen concentration, pH, concentration of HbS, temperature, pressure, ionic strength and the presence of normal hemoglobin. The consequences of polymerization are: deformation, stiffness and loss of flexibility of the red blood cells, resulting in hemolytic anemia, vaso-occlusive events and splenic function, causing an increase in susceptibility to infection. Sickle cell anemia, despite having its origin in the mutation of the beta globin gene, presents a variety of disorders such as, for example, a state of chronic inflammation that is associated with vascular injury, increased production of reactive oxygen species (ROS), hemolysis, decreased bioavailability of NO, increased production of inflammatory molecules (TNF-alpha, GM-SCF, IL-1², IL-3, M-CSF, IL-6, IL-8). Strong evidence suggests that the significant increase of fetal hemoglobin (HbF) levels provide an improvement in the clinical picture of the disease. Currently, Hydroxyurea (HU) is the only drug approved by the Food and Drug administration (FDA) for the treatment of sickle cell anemia. The mechanism of action of this drug is based on the ability to increase HbF levels and thus reduce clinical complications of the disease. However, new drugs have been studied in order to improve the prognosis of patients with sickle cell anemia. The objective of this study is to assess the anti-inflammatory ability and induction of gamma globin, constituent of HbF of the candidates derived from Thalidomide + furoxan derivatives. (AU)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

SOUZA, Cristiane Maria de. Hybrids of thalidomide and furoxan derivatives: evaluation of anti-inflammatory. 2018. Master's Dissertation - Universidade Estadual de Campinas (UNICAMP). Faculdade de Ciências Médicas Campinas, SP.