Study On Synthesis And Antitumor Activity Of New Organic Selenium Compounds

Selenium is one of the essential trace elements in human body, which is closely related to maintain and continue the human life. In the human body, Selenium is mainly exists in the form of selenium protease, for example: glutathione peroxidase. Ebselen has attracted much attention because of its anti-inflammatory, antioxidant and antitumor activity. And the study has found that the physiological activity of ebselen is similar to the GSH-Px. 1,3,4-Thi-adiazole derivatives that have antibacterial, antiviral, antitumor activity and other biological activity, has been widely used in agriculture and medicine research and application.Based on this, we used the ebselen as lead compound, designed and synthesized new sixteen organic selenium compounds which did not reported in literatures. We have confirmed the structures of these compounds by IR, 1H NMR and ESI-MS and elemental analysis methods, and evaluated for their cytotoxicity in vitro-against human cancer cells A549, SMMC-7721 and MCF-7 by CCK-8 assay.For A549 cells, all compounds showed higher activities than positive control5-fluorouracil. Whereas, most of them displayed lower antitumor activities than ethaselen.With the exception of compound 8a, the other compounds which carring various substituents all displayed increased activities in comparison to compound 8a. These results suggest that the presence of substituent groups at the phenyl ring is favorable for improving the potency of compounds against A549 cells.For SMMC-7721 cells, most of the newly synthesized compounds exhibited very good antitumor activities against SMMC-7721 cells. Especially the compound 8g which bearing4-methoxy substituent at the phenyl ring displayed very good antiproliferative effects with IC50 value of 2.08 μmol/L. Except the compounds of 8l and 8p which displayed moderate antitumor activities, the other compounds displayed higher activities than positive control ethaselen.For MCF-7 cells, all compounds showed much better potency than positive control ethaselen. Meanwhile, except the compounds of 8d, 8l and 8n exhibited moderate antitumor activity, the other compounds displayed very good antiproliferative effects within IC50 values6.04 μmol/L. Compounds 8b and 8m have displayed highly effective biological activities against MCF-7 cells with IC50 values of 2.03 and 2.06 μmol/L respectively. And the majority of them exbibited better activities than 5-fluorouracil. As compared with compound 8a, the majority of substituent groups resulted in a increase in the potency of compounds.In summary, the new sixteen organic selenium compounds we synthesized showed dif ferent anti-proliferative inhibition in three kinds of tumor cells, and most of these antic ancer activity is better than the positive control. The substituent effect against antitumor acti vity has more important significance and reference value for our future work and selected topic.