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

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.