445429-07-2Relevant academic research and scientific papers
Novel Benzohydroxamate-Based Potent and Selective Histone Deacetylase 6 (HDAC6) Inhibitors Bearing a Pentaheterocyclic Scaffold: Design, Synthesis, and Biological Evaluation
Vergani, Barbara,Sandrone, Giovanni,Marchini, Mattia,Ripamonti, Chiara,Cellupica, Edoardo,Galbiati, Elisabetta,Caprini, Gianluca,Pavich, Gianfranco,Porro, Giulia,Rocchio, Ilaria,Lattanzio, Maria,Pezzuto, Marcello,Skorupska, Malgorzata,Cordella, Paola,Pagani, Paolo,Pozzi, Pietro,Pomarico, Roberta,Modena, Daniela,Leoni, Flavio,Perego, Raffaella,Fossati, Gianluca,Steinkühler, Christian,Stevenazzi, Andrea
, p. 10711 - 10739 (2019)
Histone deacetylase 6 (HDAC6) is a peculiar HDAC isoform whose expression and functional alterations have been correlated with a variety of pathologies such as autoimmune disorders, neurodegenerative diseases, and cancer. It is primarily a cytoplasmic protein, and its deacetylase activity is focused mainly on nonhistone substrates such as tubulin, heat shock protein (HSP)90, Foxp3, and cortactin, to name a few. Selective inhibition of HDAC6 does not show cytotoxic effects in healthy cells, normally associated with the inhibition of Class I HDAC isoforms. Here, we describe the design and synthesis of a new class of potent and selective HDAC6 inhibitors that bear a pentaheterocyclic central core. These compounds show a remarkably low toxicity both in vitro and in vivo and are able to increase the function of regulatory T cells (Tregs) at well-tolerated concentrations, suggesting a potential clinical use for the treatment of degenerative, autoimmune diseases and for organ transplantation.
