Synthesis And Anticancer Activity Of2-Substituted Oxadiazole Benzisoselenazol-3(2H)-ones

Thee series of compounds were designed and synthesized according to the superpositionprinciple of biological activities. Ten compounds were designed and synthesized. All of thecompounds are novel. Antibacterial-activity of all compounds have not been reported so far.Most of oxadiazoles was synthesized from aldehyde and Semicarbazide hydrochloride byhydrazone reaction and intramolecular cyclization. Also,we synthesized some from acid.The2-Substituted oxadiazole Benzisoselenazol-3（2H）-ones were synthesized by2-amino-1,3,4-oxadiazoles and Bu-Li in new THF. The structure of all the compounds areconfirmed by IR and1H NMR.The ten compounds were tested for antiproliferative activity in vitro against the cells ofhuman cancer cell lines: SSMC-7721（human liver cancer cell）, MCF-7（human breast cancercell） and A549（human lung adenocarcinoma cell）.Most of the compounds7a-j showed moderate activity aganinst SSMC-7721cells, whilecompounds7a,7c and7g having IC₅₀values ranging from15.90to19.63μM exhibitedsimilar activity to that of ebselen (IC₅₀=18.33μM). but compound7b showed better activitythan ebselen did (IC₅₀=12.87μM). Especially,4-chlorophenyl substituent7d showed the bestantiproliferative activity (IC₅₀=4.46μM), that is much more effective than ebselen. Similarly,4-methoxy-phenyl substituent7h also showed signifacant antitumor activity (IC₅₀=5.24μM).compounds7f,7i and7j showed similar activity, but these compounds all lowered the activitycompared with7a and ebselen.Most of the compounds7a-j showed higher antiproliferative activity than that ebselendid against MCF-7cells. Expecially noteworthy is compound7d, which exhibitedsignificant antiproliferative activity against MCF-7cells (IC₅₀=1.07μM). In addition,multi-electron-donating substitution of phenyl ring displays higher antiproliferative activitythan single-electron-donating substitution of pheny ring at C-5position. For instance,compound7i showed the best antiproliferative activity (IC₅₀=1.76μM), that is much moreeffective than single-electron-donating substituents7f-7h.All the compounds7a-j showed lower antiproliferative activity than that ebselen didagainst A549cells. But compound7i remained high activity (IC₅₀=9.60μM). Moreover, theresults obtained from the observation showed that the introduction of electron-donatinggroups was effective to enhance the anticancer activity. Appearently, this class of compoundsshowed certain selectivity against different human cancer cells.