Design,Synthesis And Preliminary Bioactivity Evaluations On Hydroxamate Derivatives As HDAC Inhibitors

There are more than 7 million people who died of cancer in the world every year.Judging from information released by China Cancer Registry,there were more than 2 million suffered from cancer in our country.And there are more than 3.1 million people who are newly found suffered from cancer every year,which means 6 people were diagnosed every minute.Our country’s cancer incidence is close to Britain,America and French.The incidence has a tendency of increase year by year.The patients had reached to 9 million in 2015.It is predicted that it will increase to 12 million in 2030.However,the cure rate was less than 13%.The tumor has become a very important reason to lead to human death.At present,most of the anti-tumor agents have the disadvantages of high toxicity and low efficacy,which seriously affect the life quality of patients.How to develop new drugs with high selectivity and pharmacological action has become the focus in research of anti-cancer drugs.It is found that the pathogenesis of cancer is related to many factors.The basic unit of the human chromosome,nuclear unit,is composed of DNA and histone.And N terminal modification of lysine residues in histone H3 and H4,such as acetylation and deacetylation,plays an important role in the process of gene transcription and translation of RNA.There is a close relationship between the production of tumor and the imbalance of the level of acetylation.In 2006,the first HDAC inhibitor SAHA was approved by the FDA.So far,there have been many similar compounds were approved or entered clinical research stage.This kind of medicine is playing a more and more important role in clinic.The HDAC inhibitors are mainly composed of three parts:the surface recognition area,the linker and the zinc binding group.According to the classical pharmacophore model of HDAC inhibitors,this paper synthesized six the novel HDAC inhibitors through changing the structure of linker and introduced rhodanine or saccharin in surface recognition area.The structures of target compounds were characterized by 1HNMR,13CNMR and HRMS.In addition,the HDAC inhibitory activities and in vitro antiproliferative activities of the target compounds were detected.The potent compounds were found.That is foundation and basis for the research and development of new anticancer drugs.