Synthesis And Antitumor Activity Of Thioether Derivatives Containing1,3,4-oxadiazole And1,3,4-thiadiazole Moiety

Nowadays, the study of the biological activity and the synthetic methods of heterocycliccompounds has always been one of the most active and important research subject in theorganic chemistry. Consequently, they have already been widely utilized in the research ofpesticides, industries and medicines. They have a prominent superiority in research of thestudy of the biological activity and the synthetic methods, and a great deal of literatures havereported that many heterocyclic compounds displayed good anticancer. In recent years, thewidely use of heterocyclic in medicines has received increasing interests among researchers.In numerous developed heterocyclic compounds,1,3,4-oxadiazole derivatives and1,3,4-thiadiazole derivatives usually displayed good biological activities such as anticancer antiviral,anti-bacterial, anti-fungal, anti-inflammation, insecticidal, herbicidal, so they have receivedincreasing interests in the field of medicines and pesticides.Schiffbase compounds have special biological activities such as anticancer, antibacterial,growth inhibition and optical properties, consequently, they also have received increasinginterests among broad researchers.In order to get some high activity and new pharmacological molecules, a series of novelthioether derivatives containing1,3,4-oxadiazole and1,3,4-thiadiazole and schiffbase moietywere synthesized by means of combining the active group1,3,4-oxadiazole,1,3,4-thiadiazoleheterocycles and schiffbase moiety, according to substructure link principle and bioisosterism.Fourteen novel thioether derivatives containing1,3,4-oxadiazole and1,3,4-thiadiazole weresynthesized. All newly synthesized compounds were characterized by IR、1HNMR、ESI-MSspectra and elemental analysis. And all these produces were evaluated for their anticancer invitro against human cancer cell MCF-7, SMMC-7721and A549via CCK-8assay.The result of experiment indicates that the IC50values of6compounds are below10μmol/L among the14compounds for SMMC-7721cells, and five of them show bettercytotoxicity than Hydroxyurea against SMMC-7721cells. Especially, the compounds5d、5f、5j and5l show better cytotoxicity with IC50values of6.78、4.34、2.84and4.55μmol/L.The IC50values of9compounds are below10μmol/L among the14compounds forMCF-7cells, five of them show better cytotoxicity than Hydroxyurea against MCF-7cells.Obviously, the antitumor activity which p-substituted show better than o-substituted andm-substituted.The IC50values of6compounds are below10μmol/L among the14compounds for A549cells, which show better cytotoxicity than Hydroxyurea. Especially, the compounds5a and5cshow better cytotoxicity with IC50values of4.11and4.13μmol/L.The result of above mentioned researches have great significances in further research ofthe synthesis containing1,3,4-oxadiazoles and1,3,4-thiadiazoles, the biological activity andthe design and develop of new drugs.