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

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.