Synthesis And Antitumor Activity Of Benzisoselenazolone Derivatives Containing 1,3,4-Thiadiazole

Selenium, one of the indispensable trace elements in human body plays an important part in human health. Benzisoselenazolone which is the hotest topic of investigators has many biological activity, such as antioxidant activity, anti-cancer activity, prevent heart blood vessel of brain illness.The strong anticancer activity and the low cytotoxic of benzisoselenazolon come to peoples notice. Changing structure of benzisoselenazolon will bring anti-cancer drugs or lead compounds that have strong anticancer activity and weak side effects. 1,3,4-thiadiazole derivatives containg N, S, O atoms is a kind of five-heterocyclic ring compounds with the biological activity of antibiosis, antiberculous, antispasmodic and tanticancer. As the function center to chelating some metallic ions which exist in human body. Bond different heterocyclic rings to the 1,3,4-thiadiazole, the compounds structure of which will have different influence on the biological activities. The "-SCH2-" group was biocompatible, and it could maintain the molecular free rotation. It is beneficial to the combination between drugs and heterocyclic structures are connected by electron donating element S, which can affect its biologica lactivity by enhancing the affinity between the receptor and the ligand. Amide structure especially the structure of aromatic can form hydrogen bonding with organnic structure which is advantageous to the molecules through the menbrane, increasing the activity of compounds. Compound structure introduced in the amine is expected to be one of most efficient and selective stronger antitumor compounds.Based on the above ideas, Ebselen was used as the lead compound,17 substituted sulfur-1,3,4-thiadiazole derivatives based on benzisoselenazolone were designed and synthesized. The structure of all the target compounds were confirmed by 1R,1H NMR, ESI-MS and elemental analysis. In order to find out novel potent antitumor agents, these target compounds were evaluated for their cytotoxicity in vitro against human cancer cell A549, SMMC-7721 and MCF-7 by CCK-8 assay.Target compounds showed potent antitumor activities on three kinds of tumor cells, and some compounds exhibited better effects than positive control Ethaselen and 5-fluorouracil (5-FU) against various cancer cell lines. The results laid a foundation for further improving the potency and the selectivity of this series of compounds.