Synthesis, biological evaluation and mechanism studies of matrine derivatives as anticancer agents.

A total of five matrine derivatives were synthesized and evaluated for their anti-proliferation activity using a panel of four human cancer cell lines, including A549 lung, BT20 breast, MCF-7 breast and U2OS osteosarcoma cells. The YF3-5, YF3-7 and YF3-9, three novel compounds, demonstrated increased anti-proliferation activity compared with matrine, of which YF3-5 revealed the strongest anti-proliferation activity with a half-maximal inhibitory concentration value of 15.49-16.67 µM against the four human cancer cell lines. The anti-proliferation mechanism underlying YF3-5 was investigated in the A549 human lung cancer cell line and the results demonstrated that YF3-5 exerted its anti-proliferation activity through the induction of apoptosis and oxidative stress, in addition to arresting the cell cycle at the G1 phase in a dose-dependent manner.