Synthesis And Antitumor Activity Of Benzisoselenazole Derivatives Bearing1,3,4-oxadiazole And1,3,4-thiadiazole

A series of benzisoselenazole derivatives bearing1,3,4-oxadiazole and1,3,4-thiadiazolehave been synthesized, studied for their antitumor activity in vitro and preliminarily studiedfor the antioxidant activity of benzisoselenazole derivatives, including:1.Ten substituded benzisoselenazole derivatives bearing1,3,4-oxadiazole and1,3,4-thia-diazole were designed and synthesized and confirmed by IR、1H NMR、ESI-MS and elementalanalysis.2.In order to find out the organoselenium compound with high antitumor activity, ten tar-get compounds were evaluated for their cytotoxicity in vitro against human cancer cell A549,MCF-7and SMMC-7721by CCK-8assay. The results show that, for A549cells, the com-pounds9a、9c、9g、9h showed better antitumor activity, the compounds9b、9e、9f、9i、9j showed moderate antitumor activity, the compounds9d showed weak antitumor activity.Compared with ebselen, the antitumor activity of9a decreased and the introduction of othersubstituents all decreased antitumor activity.For MCF-7cells,the compounds9a、9e、9f、9gshowed better antitumor activity, the compounds9b、9c、9d、9h、9i、9j showed moderateantitumor activity. Compared with ebselen, the antitumor activity of9a is greatly improved.The introduction of some substituents improved the antitumor activity and the other substitu-ents made antitumor activity decreased. Especially noteworthy, the compound9e showed su-perior antitumor activity with IC50value of1.21.μmol/L. For SMMC-7721cells, the compou-nds9c、9d、9e、9g、9h、9j showed better antitumor activity, the compounds9a、9f、9i showedmoderate antitumor activity, the compounds9b showed weak antitumor activity. Comparedwith ebselen, the antitumor activity of9a decreased. The introduction of some sub-stituentsimproved the antitumor activity and the other substituents made antitumor activity decreased.Especially noteworthy, the compound9j showed superior antitumor activity with IC50value of3.14μmol/L.3.Twenty-three benzisoselenazole derivatives that synthesized by our research groupwere evaluated for their antioxidant activity in vitro by DPPH assay preliminarily. The resultsshow that, compared with the control sample of vitamin C, the antioxidant average inhibitionrates in vitro of the tested compounds reveal in different degree.In summary, the introduction of1,3,4-oxadiazole and1,3,4-thiadiazole has a significantinfluence on the activity of benzisoselenazole derivatives. This conclusion lays foundation forfurther exploration of the relationship between structure-activity relationship with antitumormechanism.