Conformations, DNA binding parameters, and antileukemic activity of certain cytotoxic protoberberine alkaloids.
The tetrahydroprotoberberine alkaloids 5 and 7 possessing a trans-quinolizidine conformation display in vitro KB cytotoxicities in contrast to their corresponding diastereomers 4 and 6 which exist in the cis-quinolizidine conformation and are much less toxic. The DNA-binding parameters of these compounds as well as the protoberberine salts 1, 8, and 9 have been examined by equilibrium dialysis. Only the quaternary salts bind to DNA. The alcohol 5 showed low in vivo activity against leukemia P388 systems, while the quaternary salts 8 and 9 proved to be toxic to the host.
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001599:Berberine / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology*; D001600:Berberine Alkaloids / Q000494:pharmacology*; D004247:DNA / Q000378:metabolism*; D003956:Dialysis; D007939:Leukemia L1210 / Q000188:drug therapy; D007942:Leukemia, Experimental / Q000188:drug therapy; D051379:Mice; D008968:Molecular Conformation; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D001600:Berberine Alkaloids; D001599:Berberine; D004247:DNA