Synthesis and antitumor evaluation of arctigenin derivatives based on antiausterity strategy.

Abstract A series of new (−)-arctigenin derivatives with variably modified O -alkyl groups were synthesized and their preferential cytotoxicity was evaluated against human pancreatic cancer cell line PANC-1 under nutrient-deprived conditions. The results showed that monoethoxy derivative 4i (PC 50 , 0.49 μM), diethoxy derivative 4h (PC 50 , 0.66 μM), and triethoxy derivative 4m (PC 50 , 0.78 μM) showed the preferential cytotoxicities under nutrient-deprived conditions, which were identical to or more potent than (−)-arctigenin ( 1 ) (PC 50 , 0.80 μM). Among them, we selected the triethoxy derivative 4m and examined its in vivo antitumor activity using a mouse xenograft model. Triethoxy derivative 4m exhibited also in vivo antitumor activity with the potency identical to or slightly more than (−)-arctigenin ( 1 ). These results would suggest that a modification of (−)-arctigenin structure could lead to a new drug based on the antiausterity strategy.