A Novel Histone Deacetylase Inhibitor Was Developed

According to the national cancer Statistics released by the National Cancer Center in 2019,cancer has become one of the top public health problems that seriously threaten the health of the Chinese population.In recent years,histone deacetylases have received more and more attention as a target of anticancer drugs.Hydroxamic acid inhibitors are the most studied and applied histone deacetylase inhibitors at present.However,hydroxamic acid group,as zinc ion binding group,is easily affected by hydrolysis due to its instability.In order to obtain more stable antitumor drugs in vivo,the structure of hydroxamic acid was modified and optimized in this paper.The main contents of this paper are as follows:The histone deacetylase inhibitors with benzoboric acid and hydrazine as zinc ion binding groups were designed and synthesized.According to the research,the stability of phenylboric acid and hydrazide groups in organisms is very good,not easy to inactivate.At the same time,phenylboric acid and hydrazine can form hydrogen bonds with histone deacetylase due to their own structural characteristics,so as to enhance the ability of enzyme recognition.Therefore,16 kinds of benzene boric acid compounds with benzene boric acid structure were designed and synthesized,and the cell inhibition rate was determined.At the same time,a feasible synthesis scheme was designed and the reaction conditions were optimized.The purpose of this project is to discover new histone deacetylase inhibitors,and to design and synthesize new histone deacetylase by cross complementation of biochemistry and pharmaceutical chemistry.Through the experiment of the inhibition rate of phenylboric acid compounds on tumor cells,it can be seen that the inhibition effect of phenylboric acid inhibitors on cancer cells is poor,with the inhibition rate not exceeding 16%on average.In the synthesis route of hydrazine inhibitors,it was found that nitrobenzene p-trifluoromethyl was the substituent with the highest yield of 94.7%,which indicated that the synthesis route of hydrazine was feasible and provided a good idea and direction for the development of new hydrazine histone deacetylase inhibitors.