Synthesis and Pharmacological Evaluation of new hybrid compounds useful to treat sickle cell disease symptoms

• Grant number: 11/15204-5
• Support Opportunities: Scholarships in Brazil - Master
• Effective date (Start): March 01, 2012
• Effective date (End): June 30, 2014
• Field of knowledge: Health Sciences - Pharmacy - Medicines Analysis and Control
• Principal Investigator: Jean Leandro dos Santos
• Grantee: Thaís Regina Ferreira de Melo
• Host Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil
• Associated scholarship(s): 13/04244-1 - Synthesis, structural characterization and NO-donor evaluation of hybrid compounds useful to treat sickle cell disease symptoms, BE.EP.MS

Abstract

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.

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

FERREIRA DE MELO, THAIS REGINA; CHELUCCI, RAFAEL CONSOLIN; LOPES PIRES, MARIA ELISA; DUTRA, LUIZ ANTONIO; BARBIERI, KARINA PEREIRA; BOSQUESI, PRISCILA LONGHIN; GOULART TROSSINI, GUSTAVO HENRIQUE; CHUNG, MAN CHIN; DOS SANTOS, JEAN LEANDRO. Pharmacological Evaluation and Preparation of Nonsteroidal Anti-Inflammatory Drugs Containing an N-Acyl Hydrazone Subunit. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 15, n. 4, p. 17-pg., 2014-04-01. (11/15204-5, 12/50359-2)

FERREIRA DE MELO, THAIS REGINA; CHELUCCI, RAFAEL CONSOLIN; LOPES PIRES, MARIA ELISA; DUTRA, LUIZ ANTONIO; BARBIERI, KARINA PEREIRA; BOSQUESI, PRISCILA LONGHIN; GOULART TROSSINI, GUSTAVO HENRIQUE; CHUNG, MAN CHIN; DOS SANTOS, JEAN LEANDRO. Pharmacological Evaluation and Preparation of Nonsteroidal Anti-Inflammatory Drugs Containing an N-Acyl Hydrazone Subunit. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 15, n. 4, p. 5821-5837, APR 2014. (12/50359-2, 11/15204-5)

CHELUCCI, RAFAEL CONSOLIN; DUTRA, LUIZ ANTONIO; LOPES PIRES, MARIA ELISA; FERREIRA DE MELO, THAIS REGINA; BOSQUESI, PRISCILA LONGHIN; CHUNG, MAN CHIN; DOS SANTOS, JEAN LEANDRO. Antiplatelet and Antithrombotic Activities of Non-Steroidal Anti-Inflammatory Drugs Containing an N-Acyl Hydrazone Subunit. Molecules, v. 19, n. 2, p. 2089-2099, FEB 2014. (12/50359-2, 11/15204-5)

Academic Publications

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

MELO, Thaís Regina Ferreira de. Síntese e avaliação farmacológica de novos compostos híbridos úteis para tratamento das complicaçôes da anemia falciforme. 2014. Master's Dissertation - Universidade Estadual Paulista (Unesp). Faculdade de Ciências Farmacêuticas. Araraquara Araraquara.