[Antitumor effect of etoposide and its analogs]

The antitumor activity of etoposide and its nine analogs including podophyllotoxin, the mother compound of etoposide, against Hela cells and mouse leukemia L1210 was investigated in vitro and in vivo, respectively. Etoposide showed antitumor effect against HeLa cells. Against mouse leukemia L1210, etoposide showed an excellent antitumor effect and about 80% of treated animals survived beyond the test period of 2 months. Podophyllotoxin, 4'-demethylpodophyllotoxin and 4'-demethylepipodophyllotoxin excluding an ethylidene glucose group had more anti-HeLa, but much less anti-L1210 activity than etoposide. 3'-Demethyletoposide showed only 1/25 of the anti-HeLa activity of etoposide, while the anti-L1210 activity was almost the same as that of etoposide. The anti-HeLa activity of 4'-demethylepipodophyllotoxin beta-D-glucoside excluding on ethylidene group and 4'-demethylepipodophyllotoxin ethylidene alpha-D-glucoside were only 1/180 and 1/26 that of etoposide, respectively. Their anti-L1210 activities were also low and the maximum T/C values were 154 and 135%, respectively. Both of two picro compounds, picroetoposide and 4'-demethylepipicropodophyllotoxin beta-D-glucoside, hardly showed any antitumor activity. 4'-O-glucuronyletoposide, the main metabolite of etoposide in humans and dogs, had little anti-HeLa activity.