Multidrug-resistant cancer cell susceptibility to cytotoxic quassinoids, and cancer chemopreventive effects of quassinoids and canthin alkaloids.

Abstract Twenty-three quassinoids ( 1 – 23 ), which were isolated previously from Simaroubaceous plants, were evaluated for cytotoxicity against three multidrug-resistant cancer cell lines, KB-VIN, KB-7d, and KB-CPT. Nine compounds ( 2 – 7 and 9 – 11 ) showed significant cytotoxicity in all three cell lines. Compounds 1 , 12 – 14 , 17 , and 20 demonstrated significant activity against the KB-7d and KB-CPT cell lines, and compounds 18 , 19 , and 23 revealed notable activity only against KB-7d cells. Structure–activity relationships were drawn based on these data. In addition, six quassinoid derivatives ( 24 – 29 ) and four canthin alkaloids ( 30 – 33 ), which were isolated from Brucea antidysenterica , were examined for their inhibitory effects on 12- O -tetradecanoylphorbol-13-acetate (TPA) induced Epstein–Barr virus early antigen (EBV-EA) activation as cancer chemopreventive agents. All of these compounds demonstrated significant inhibitory effects against EBV-EA activation.