Orychophragines A-C (1-3), three new alkaloids with an novel 2-piperazinone-fused 2,4-dioxohexahydro-1,3,5-triazine skeleton, were isolated from the seeds of Orychophragmus violaceus. Their structures were established on the basis of spectroscopic analysis and X-ray crystallographic analysis. Orychophragines A (1) exhibited remarkable cytotoxicity against HepG2, A549, Hela, and HCT-116 cells with IC(50) values of 7.73, 10.79, 11.91, and 9.93 muM, respectively. Orychophragines C (3) showed moderate (60)Co gamma radiation protection activity in HUVEC cells. A plausible biosynthetic pathway for 1-3 was proposed.