Synthesis of benzo[c]phenanthridine derivatives and their in vitro antitumor activities

Aiming at the development of anticancer agents by modification of phenolic benzo[c]phenanthridine alkaloid, additional hydroxyl group was put on C10 position of fagaridine (1) by a biomimetic synthetic procedure to afford 10-hydroxyfagaridine (12). All of the synthetic intermediates were also screened in vitro antitumor activities against five different cell lines as well as 12. Among them the representative cytotoxic results are shown as follows; p-quinone (11) [ED(50) (A549=0.22 mu g/ml), (HCT15=0.21 mu g/ml), fagaridine (1) (HCT 15=0.41 mu g/ml), olefin (6) (HCT 15=0.06 mu g/ml), acetal (7) (SKMEL-2=0.07 mu g/ml), dihydrofagaridne (10) (A549=0.38 mu g/ml), 10-hydroxyfagaridine (12) (A 549=0.45 mu g/ml). From these observation three main remarks can be drawn; (i) the iminium part of benzo[c]phenanthridine is not essential for showing acitvities, (ii) the additional hydroxyl group did not contribute to enhance the cytotoxicity, (iii) the 3-arylisoquinolin-1(2H)-one derivatives were found to display significant in vitro antitumor activity.