In vitro cytotoxic activities of 24 quaternary protoberberine alkaloids rel
ated to berberine have been evaluated using a human cancer cell line panel
coupled with a drug sensitivity database. Extending the alkyl chain at posi
tion 8 or 13 strongly influenced the cytotoxic activity, that is, relative
lipophilicity as well as the size of the substituent affects cytotoxicity.
The highest level of activity was observed in 8- or 13-hexyl-substituted de
rivatives of berberine. Structure - activity relationships are described.