Design And Synthesis Of Novel Histone Deacetylase Inhibitor Of Prodrug

The studies of Vorinostat HDACi are more and deeper in present researches, which have shown a good anti-tumor activity whatever in vivo or in vitro.However, SAHA exhibits several drawbacks. These properties such as lower water solubility and poorer cell permeability can limit the effectiveness of their treatment. Therefore, it needs to develop new improved performance with hydroxamic acid derivatives. We designed new prodrugs from the SAHA with dicarboxylic acid, and they have good solubility, cell permeability and druggability.In this study, we use HDACs as a target and SAHA as leading compounds to design a new type of SAHA derivatives. We synthesized 16 new compounds which were not reported using CDI as a catalyst, the chemical structure by 1HNMR,13CNMR, ESI-MS spectral confirmation. Inhibition of enzyme activity by in vitro testing and anti-tumor cell proliferation assay was found to have good activity, some of then are better than SAHA.