Determination Of The Design, Synthesis And Biological Activity Of New Histone Deacetylase Inhibitors

Cancers are threatening our mankind s life and health. According to the WHO' s statistics data, there have been about 7, 000, 000 people died of cancers in the world every year, while about 1, 500,000 people died of cancers in China. Now, the amount of cancer patients is still increasing in China, and this number is by 1,800,000 every year. So the task of precaution and therapy against cancers are very arduous. Histone Deacetylase Inhibitors(HDACI) induce terminal cell differentiation and/or apoptosis and regulate the transcription in cancer cells. And so that the HDACI can realize the aim of inhibiting the tumor cells' multiplication. It is very significant for our country in the WTO that we should develop new drugs with our own intellectual property by computer-aided drug design (CADD) and Me-too Drug Design. Here the CADD acts as the way to find lead compounds while Me-too Drug Design acts as the way to optimize the lead compounds.This issue is just a part of a Chinese Scientific Fund' s item (No. 30472091), which has been taken on by Wu Song' s Researching Group. In this part, four types of compounds such as carbamides, acylamides, bishydrazides, hydroxamates, and so on, have been synthesized. The total numbers of compounds are 68, including 30 target compounds, 38 intermediate compounds, 44 compounds are unreported. All the target compounds confirmed by 'H-NMR and MS, and evaluated their biological activities in vitro, among which 4 compounds showed stronger activity than the positive contrast compound SAHA.