Design、Synthesis And Antitumor Activity Study Of Aza-diphenyl Ketene Curcumin Analogs

Cancer is one of the the most grave health issues,which features proliferation and spread of uncontrolled cell. At present in China and even the world, cancer has become the second leading cause of human death.Therefore,the investigator always pursue the goal that they should develop efficient.safty and low toxicity anticancer drug and totally conquer cancer.The turmeric rhizome parts contains curcumin which shows a variety of pharmacological activity.In addition, many literature have clearly reported that curcumin has significant anti-tumor activity and inhibits the growth and spread of a varity of cancer cells, which can be used as antimutagen and anti-cancer promotor with many advantages such as broad anti-tumor spectrum, anti-multidrug resistance and a few toxic side-effects. What’s more, curcumin has significant inhibitory effect on both the tumor ocurrence and development stages,even can play a variety of performance on the same tumor. So, there is a new direction that we research and develop new drugs based on Chinese herbal medicine active ingredient as lead compounds. In this paper we synthesis target compounds.which taked diphenyl ketene curcuminoids as lead compound and was auxiliaried the prediction and structural modification of computational chemistry3D-QSAR.The next is to value the anti-tumor activity in vitro. We hope to get good active compounds,which featured broad anti-tumor spectrum, low toxicity, anti-multidrug resistance as precursor of anticancer drugs.Based on the anti-cancer activity research work of diphenyl ketene owned by our laboratory and auxiliaried the prediction and structural modification of computational chemistry3D-QSAR, The main task of our research to synthesis three series of new diphenyl ketone of curcumin derivatives which contained15symmetrical and4unilateral piperidine ketone with the1-N-alkylation substitution, based on the parent structure of curcumin. The synthesis route contain three-step reaction of alkylation, hydroxyl protection, aldehyde ketone condensation.utilizing the4-piperidine ketone hydrochloride hydrate as raw material. And then all the compoundwere characterized by means of1HNMR. spectrum and mass spectrum to indentified target compounds.Then all the compound were valued anti-tumor Pc-3activity by MTT assay with curcumin as positive control drug.Results In showed that most the target compound had a good anti-tumor activity, for example,the1C50value of compound a3and b3were0.54μmol and0.25μmol, obviously better than the leads compound curcumin,so far,the bioavailability study of these compounds is to be extended further and practice has proved that modifying the structure of natural small molecule is an effective way to look for new antitumor drugs.