ANTITUMOR ACTIVITY OF 4-〔4"-(2", 2", 6", 6"-TETRAMETHYL-1"-PIPERIDINYOXY)AMINO〕-4'-DEMETHYLEPIPODOPHYLLOTOXIN / 中国药理学通报

ABSTRACT

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.