某些细胞毒性原小檗碱生物碱的构象、DNA结合参数及抗白血病活性

Conformations, DNA binding parameters, and antileukemic activity of certain cytotoxic protoberberine alkaloids.

作者信息

Cushman M, Dekow F W, Jacobsen L B

出版信息

J Med Chem. 1979 Mar;22(3):331-3. doi: 10.1021/jm00189a025.

Abstract

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.

摘要

具有反式喹诺里西啶构象的四氢原小檗碱生物碱5和7表现出体外KB细胞毒性，而它们相应的非对映异构体4和6以顺式喹诺里西啶构象存在，毒性要小得多。这些化合物以及原小檗碱盐1、8和9的DNA结合参数已通过平衡透析进行了检测。只有季铵盐与DNA结合。醇5对白血病P388系统显示出低体内活性，而季铵盐8和9对宿主有毒。