The influence of certain colchicine derivatives on the growth characteristics of L cells.

Colchicine and its derivatives (demecolcine, 2-demethyldemecolcine and acetylated 2-demethyldemecolcine) blocked the mitotic activity of L cells and inhibited proliferation and DNA synthesis. This effect depended on the length of the exposure and the concentration of the substances tested (from 0.05 micrograms/ml up to 2.6 micrograms/ml). The greatest values of plating efficiency, cell proliferation, mitotic index and inhibition of DNA synthesis, respectively, were found after the application of colchiciline (0.2 micrograms/ml). These effects were reversible, since L cells underwent regeneration of the mitotic spindle and renewal of their function after the removal of colchiciline. Reversible effects were much less with other colchicine derivatives tested. The different effects of colchicine and its derivatives were due to their chemical structure, which determines the interactions with respective L cell receptors and thus modifies the mechanism of action on the mitotic apparatus of L cells.

Effect of colchicine derivatives on the antibody response induced in vitro.

Effect of 44 colchicine derivatives on the induction of antibody response in tissue cultures was tested. Lymphatic cells from the spleen of BALB/c mice were cultivated with antigen (sheep red blood cells) and the number of antibody forming cells was determined by the plaque technique. Most compounds with the immunoinhibitory effect are derived from the colchicine formula (I). The effect was increased by introducing ethyl, formyl or methylenedioxide groups. Colchinols exerted very good immunoinhibitory effect resulting by contraction of tropolone ring C into the aromatic one. A complete loss of the effectivity was detected in the case of glucoside of colchicine, colchiceine, isocolchicine, oxycolchicine, allocolchicine and in lumiderivatives of colchicine. No correlations between the immunoinhibitory effect, toxicity and stathmokinetic effect were detected: decrease of cell viability and arrest of mitoses were not observed in cultured lymphocytes within the range of the immunoinhibitory effect. The effect of colchicine derivatives was manifested as the inhibition of lymphocyte blastogenesis, which is probably the result of membrane transport blockade.

Transformation of alkaloids of the Colchicine type in leaves and flowers of Colchicum autumnale and C. byzantinum.

It was found that the so far described variations in the content of colchicine alkaloids in leaves and flowers of Colchicum autumnale L. and C. byzantinum Ten. are due to enzymatic O-demethylation and degradation of colchicine (I), N-deacetyl-N-formylcolchicine (XI), and demecolcine (XVII) during drying and storing of the plant material. A simplified method was elaborated to separate the neutral, phenolic, basic, and basic-phenolic fractions of tropolone alkaloids.

[Isolation and chemistry of the alkaloids from plants of the Papaveraceae, LXXXI Glauca - a new section of the genus Papaver]. / Isolierung und Chemie der Alkaloide aus Pflanzen der Papaveraceae, LXXXI.

On the basis of alkaloidal, morphological and chromosomal studies, the section Mecones Bernh. (Syn.: Papaver L., sect. Papaver) has been subdivided into two sections. Thus the new section Glauca J. Novak includes the species Papaver glaucum Boiss. et Hausskn., P. gracile Auch. and P. decaisnei Hochst. et Steud., whereas the section mecones Bernh. only the species P. somniferum L. and P. setigerum Dc. The major alkaloids of the species of the section mecones are the morphinane alkaloids morphine and codeine, whereas those of the section Glauca the rhoeadine and the papaverrubines. The section mecones has the basic chromosome number x = 11, and the section Glauca x = 7. The basic chromosome numbers have been correlated with the morphological features.

[Biochemical changes in guinea pigs after the application of high doses of ascorbic acid]. / Biochemische Befunde bei Meerschweinchen nach Applikation hoher Dosen Askorbinsäure.

The effect of high doses of ascorbic acid (AA) (200 mg/kg body weight, s. c.) on the values of some biochemical parameters has been studied in guinea pigs (glucose, lactic acid, SH substances and GSH in blood, proteins and urea, and the LDH, MDH, ASAT, ALAT, and gamma-GT activities in the serum, the acid phosphatase activity in the liver, the gamma-GT activities in the liver and the kidney, and on the levels of SH substances and GSH in various organs). Ascorbic acid was administered to the animals in a single dose or in dialy doses for different periods (4 days, 2 weeks, and 7 weeks). The majority of the studied parameters showed a transient increase or decrease of the values which, however, after long term AA administration mostly returned to normal values. After 7 weeks, the level of urea in the serum remained increased (by approximately 30%) contrary to the decreased level of lactic acid, the gamma-GT activity in the serum, and the GSH level in some organs. In the experimental series carried out in the different seasons of the year, the results differed in some cases especially after short term AA administration. However, in a few cases, even the values obtained from the control animals tended to differ. If similar changes are to be expected in man after AA administration, then on the basis of our results it can be assumed that in the indicated cases the therapeutic long-term application of large AA doses does not present any hazard to the patient.

Isolation and chemistry of alkaloids from plants of the family Papaveraceae LXVII: Corydalis cava (L.) Sch. et K. (C. tuberosa DC).

From Corydalis cava (L.) Sch. et K. (C. tuberosa DC) (Papaveraceae: genus Corydalis Med.), a mixture of alkaloids (0.53%) was isolated. The main alkaloid was (+)-bulbocapnine, and the minor alkaloids were coptisine, (+)-domestine, adlumidiceine, (+)-predicentrine, protopine, (-)-capnoidine, (+)-stylopine, (+)-isoboldine, 8-oxocoptisine, 1,2-methylenedioxy-6a,7-dehydroaporphine-10,11-quinone, and corysamine. In addition, fumaric acid was obtained. Coptisine, adlumidiceine, predicentrine, 8-oxocoptisine, corysamine, 1,2-methylenedioxy-6a, 7-dehydroaporphine-10,11-quinone, and isoboldine were found in C. cava for the first time, but rhoeadine and papaverrubine alkaloids were not detected. Predicentrine and isoboldine were identified on the basis of the UV, IR, mass, and PMR spectra.