Synthesis And Activity Of Novel Chalcone And Heterocyclic Derivatives

Aminodisulfide compounds are a natural small molecule that is effective in chelating heavy metals and selectively enhancing the two-phase enzyme activity as a single functional inducer,therefore widely used in clinical pharmacological studies.The chalcone compound has a 1,3-diphenyl-2-propen-1-one structure,which capable of binding to different drug action targets to exert its pharmacological activity.Thus,the study of these two types of natural small molecules has received extensive attention and research in the field of pharmacology.Based on the literature,the study group,which based on the full study of the structure-activity relationship and pharmacological activity of the aminodithioformate and chalcone structural compounds,retained the integrity of the chalcone active fragment.Condensation reaction and fight the principle of the biological groups of linear acid halide,aminodithioformate,triazole and other active fragments were connected to the chalcone molecules.Respectively,the synthesis of 43 target compounds.The Specific research work is as follows:The first part is the synthesis of heterocyclic chalcone derivatives.Derivatives Synthesis of amino chalcone and azapyalone compounds mainly through the Claisen condensation reaction.The next step is to use the key intermediates synthesized,according to the principle of drug stitching,targeted design and synthesis of three series of 43 new chalcone derivatives.The second part is the bioassay evaluation.The anti-tumor-related activity evaluations were carried out by using the MTT method for the 43 novel chalcone derivatives synthesized.The main selectivity is human prostate cell,gastric cancer cell and human esophageal cancer cell.The results showed that most of the linear acid halide chalcone compounds and aminodithioformate and chalcone derivatives had good antitumor activity,in which compounds Ⅰ-1,Ⅰ-2,Ⅰ-4,Ⅱ-4,Ⅱ-7,Ⅱ-10,Ⅱ-15 showed better antitumor activity.One of the best activity is Ⅱ-4.When the linear acyl halide and aminodithioformate active molecules were introduced,the drug activity was found to be effectively increased.However,on the basis of the introduction of triazole structure,the activity is reduced.The work of this group provides a basis for further finding compounds with better antitumor activity and higher bioavailability.