The antiumor activity of a new podophyllotoxin spin-labeled derivative, 4 -C 4 "-( 2 ", 2", C", 6"-tetramethyl- 1 "-piperidinyoxy ) amino]-4'-demethylepipodophyllotoxin ( GP-7 ) was studied. It was found that the growth of transplanted mouse tumors S180, HePS and Lewis lung cancer was markedly inhibited by GP-7. At a dose of 7.5-20 mg/kg, the inhibition rates of it against Sl80, HePS and Lewis lung cancer were 36.0-58.4, 29.6-60.0, and 27.2-46.5 % respectively. The toxicity of GP-7 was low, as indicated by the LD50 value of 231.2 mg/kg which was 3.3 times higher than that of etoposide ( VP-16 ) . On the other hand, the effects of GP-7 on spleen index and thymus index of mice bearing S180 tumor were remarkably lower than that of VP-16. In vitro GP-7 exhibited marked inhibition effects against L1210 and SGC-7901 cells. After exposure of L1210 cells to GP-7 and VP-16 5 mg/L for 24 h, the. inhibition rates were 75.5 and 73.6 %. after exposure of SGC-7901 cells to GP-7 and VP-16 5 mg/L for 72 h, the inhibition rates were 81.4 and 84.2 %. The new podophyllotoxin derivative GP-7 was similar to its structure analogues, clinical drug VP-16, in antitumor activity, while the toxicity of it was much lower than that of VP-16.

It was found that the proliferation of mice L7712 leukemic cells in vitro was markedly inhibited by 5 mg/L GP1 and VP10 The inhib itory rate increased with the incubation time. At a concentration of 0 .04-20mg/L, the mitotic index ( MI ) of GP1 group increased, but the MI of VP16 group decreased. After L7712 cells were treated with GP, 5 mg/L for 12 h the MI reached the highest point which was 8 times as high as that of the control, at the same time, the MI of VP16 ( 5 mg/L) group was about one-third of that of the control. The result of the combination of GP1 with VP16 showed that VP16 could antagonize the effect of GP on MI of L7712 cells. After being treated by GP1 and VP18 for 24 h, serious damage of L7712 cells could be observed. Both drugs inhibited the incorporation of (3H) TdR into DNA of S180, ascitic hepatoma (AH), L1210 and L7712 cells incubated for 24 h. It was further observed that S180 and L7712 cells were more sensitive than other cells to both drugs.