Biological activity of metabolites of the incubated alkaloids by cultured cells of several species of Papaveraceae

1. 研究发现，原小檗碱< α > - n -甲基盐在一些罂粟属植物和愈伤组织培养物中通过原碱转化为苯并[c]菲菲啶。目前已经证实，在连柱属植物愈伤组织培养中，反式和顺式13-甲基原小檗碱n -季铵盐可以转化为类似于丁香碱的物质，反式和顺式13-羟基原小檗碱n -季铵盐可以转化为13-氧基原托碱，后者可以转化为螺苯基异喹啉和苯并地氮平。< α > -和< β > - n -季铵盐，< α > - n -甲基盐具有顺式喹啉环进行生物转化。结果还表明，螺苯基异喹啉的脂肪族o -甲基是由原嘌呤骨架的n -甲基产生的。甲基从N向O迁移发生在环重排过程中。C-1上有甲氧基的(-)-反式-13-羟基原小檗碱也被生物转化为13-氧原托碱和苯并地氮平类生物碱。邻苯二代异喹啉类生物碱通过细胞培养被简单的四氢异喹啉和meconin代谢。一些前体已显示出生物和药理学活性。为了获得立体结构与生理活性之间的关系，阐明立体选择性生物转化的机制，对原小檗碱-、原托宾-苯并[c]菲并苯胺-和邻苯二甲酸二异喹啉类生物碱进行了构象分析。得到了这些生物碱构象的一些新信息。原小檗碱-、原托碱-和苯并[c]菲咯啶类生物碱的衍生物进行了抗白血病筛选和抗菌试验。获得了一些关于抗菌作用的新信息。许多化合物被认为对小鼠白血病p388无活性。对部分生物碱的检测结果因其毒性而受到限制。

1. It has been found that the protoberberine <alpha> -N-methyl salts were transformed in some Papaverous plants and the callus cultures via the protopines into benzo[c]phenanthridines. At present bioconversions in callus cultures of Corydalis species of both trans- and cis-13-methylprotoberberine N-quaternary salts into a corycavine analogue as well as of both trans- and cis-13-hydroxyprotoberberine N-quaternary salts into 13-oxoprotopine-type, which is biotransformed into spirobenzylisoquinoline and benzindenoazepine, are demonstrated. Of <alpha> - and <beta> -N-quaternary salts, <alpha> -N-methyl salt bearing a cis quinolizidine ring was biotransformed. It was also demonstrated that the aliphatic O-methyl group of the spirobenzylisoquinoline arises from the N-methyl group of the protopine skeleton, ie. migration of the methyl group from N to O occurs during the ring rearrangement. (-)-Trans-13-hydroxyprotoberberine having the methoxyl group at C-1 was also bioconverted to 13-oxoprotopine- and benzindenoazepine-type alkaloids. Phthalideisoquinoline alkaloids were metabolized the simple tetrahydroisoquinoline and meconin by cell cultures.2. A number of the precursors have demonstrated biological and pharmacological activities. In order to obtain the relationships between stereostructure and physiological activity and to clarify the mechanism for stereoselective bioconversion, conformational analyses of protoberberine-, protopine-benzo[c]phenanthridine-, and phthalideisoquinoline-type alkaloids were carried out. Some new informations for conformation of these alkaloids were obtained.3. The derivatives of protoberberine-, protopine-, and benzo[c]phenanthridine-type alkaloids were submited to antileukemic screening and antibacterial tests. A number of new informations were obtained on antibacterial action. Many compounds can be considered inactive for leukemia p388 in mice. The results on some alkaloids were limited because of toxicity.