Synthesis And Antitumor Activity Of Novel Coumarin Derivatives

Coumarin is a kind of important heterocyclic compounds widely found in nature.Coumarin derivatives have a variety of biological activities,such as anticoagulation,anti-oxidation,anti-inflammation,anti-bacterial,anti-viral,anti-tumor and so on.In this dissertation,we use the molecular combination principle of medicinal chemistry,combine the active fragments such as 3,4,5-trimethoxyphenyl,1,2,3-triazole,amide with the mother nucleus of coumarin to synthesize three series coumarin compounds and evaluate their anti-tumor activity in vitro,aims to obtain compounds with good anti-tumor activity.The specific research contents are as follows:1.On the basis of literature research and previous work by the research group,synthesize 23 series?coumarin amide derivatives.1,2,3-triazole was introduced into the backbone of series?,then use it as a new linker to link the amide structure and coumarin to synthesize 23 series?1,2,3-triazole coumarin derivatives.Based on CA-4 analogues and 4-arylcoumarins as the basic skeleton of series III was designed,acyl groups were introduced into 4-arylcoumarins to synthesize 16 4-acylcoumarin derivatives.Totally 62 coumarin derivatives were synthesized,of which 57 were not reported.All the target compounds were determined.2.The antitumor activities of all the target compounds against human gastric cancer cell line MGC-803,human prostate cancer cell line PC-3 and human esophageal cancer cell line EC-109 were evaluated by MTT method.The compounds with good anti-tumor activity were screened out for further mechanism research.The results showed that most of the compounds have inhibitory effects on MGC-803 cells,among them 27e and 27g were the most potent with the IC₅₀ values were 0.10?M and 0.15?M respectively,which were much better than positive control5-fluorouracil.Compound 13g had the best inhibitory effect on PC-3 and EC-109cells,with IC₅₀ values were 0.69?M and 12.85?M respectively.In addition,the inhibitory effect of compound 12b,13e and 13g against three kinds of tumor cells was better than that of the positive control drug 5-fluorouracil.3.The structure-activity relationship of each series of compounds was preliminarily analyzed in order to provide a direction for the synthesis of these compounds with high activity in the future.