Synthesis And Anti-Tumor Evaluation Of Caffeoyl Derivatives In Vitro

Caffeoyl derivatives are widely distributed in nature,such as caffeic acid phenethyl ester（CAPE）,Chlorogenic acid,L-Cichoric acid,rosmarinic acid etc.In recent years,the structure-activity relationship of caffeoyl derivatives was studied intensively,and it was revealed that the caffeoyl derivatives have simple structure and show a lot of biological activities,such as antibacterial,anti-oxidation,anti-HIV-1,antitumor and so on.Having advantages of low toxicity,anti-drug-resistant and easy preparation,these caffeoyl derivatives attracted more and more attention.In this study,we investigate further the antitumor of caffeoyl derivatives based on previous research work.We used “one-pot method” and “mixed carbonic anhydride method”to synthesize the caffeoyl derivatives via the substitution reaction,nitration reaction and esterification reaction.Nineteen caffeoylderivatives including 6 new compounds were synthesize,and their antitumor activities were evaluated by MTT assay in vitro,and 4compounds showed strong antitumor activities.These compounds were tested by the fluorescence staining and flow analysis.The results showed that most of caffeyol derivitives have strong inhibitory effect on the growth of tumor cells,caffeic adamantyl ester and2-NO₂ caffeic bornyl ester can significantly inhibit the growth of SW620,and 5-NO₂ caffeic adamantyl ester and caffeic adamantyl amine can significantly inhibit the growth of MBA-MD-231,the compounds exhibited higher antitumor activities than the positive control drug.The caffeic adamantyl ester and 2-NO₂ caffeic bornyl ester induced the former and latter apoptosis of SW620,5-NO₂ caffeic adamantyl ester and 5-NO₂ caffeic adamantyl amine induced the former and latter apoptosis of MBA-MD-231.The results are valuable in searching for lead compounds with potent antitumor activities,the structure-activity relationship of which are worth of being studied further.