Synthesis of selective HDAC 1 and 2 inhibitors designed as fetal hemoglobin inducers

• Grant number: 19/09456-3
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: August 01, 2019
• End date: September 30, 2020
• Field of knowledge: Health Sciences - Pharmacy
• Principal Investigator: Jean Leandro dos Santos
• Grantee: Beatriz Silva Urias
• Host Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil

Abstract

Sickle Cell Anemia (SCA) is a genetic hemoglobinopathy characterized by chronic hemolytic anemia, pain and damage to various organs, leading to wide clinical variability and decreased life expectancy. Increased levels of fetal hemoglobin (HbF) is a validated approach to treatment. Among the strategies described to elevate HbF levels, the inhibition of the enzymes Histone Deacetylase (HDAC) classe I, especially HDAC-1 and HDAC-2, promotes an increase in HbF production without causing changes in cell cycle and cell proliferation. Thus, in this project, in continuity with the research aim to identify HbF inducers, we propose the synthesis of new derivatives designed as selective inhibitors for HDAC-1 and HDAC-2 that may constitute a new alternative for the treatment of SCA.

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)

URIAS, BEATRIZ SILVA; PAVAN, ALINE RENATA; ALBUQUERQUE, GABRIELA RIBEIRO; PROKOPCZYK, IGOR MUCCILO; FERREIRA ALVES, TANIA MARA; FERREIRA DE MELO, THAIS REGINA; RODRIGUES SARTORI, GERALDO; MARTINS DA SILVA, JOAO HERMINIO; CHIN, CHUNG MAN; DOS SANTOS, JEAN LEANDRO. Optimization of Resveratrol Used as a Scaffold to Design Histone Deacetylase (HDAC-1 and HDAC-2) Inhibitors. PHARMACEUTICALS, v. 15, n. 10, p. 18-pg., 2022-10-01. (18/11079-0, 17/07789-0, 18/19523-7, 15/19531-1, 15/21252-3, 19/09456-3)