Synthesis and anti-tumor evaluation of panaxadiol derivatives

Determination of cucumarioside A2-2 in mouse spleen by radiospectroscopy, MALDI-MS and MALDI-IMS

Panaxadiol (PD), a diol-type ginseng saponin, with a dammarane skeleton plays a potential role in the apoptosis of tumor cells. In this study, 28 oxidation and nitrogen hybrid derivatives of PD were synthesized, of which 20 were novel compounds. All the obtained compounds were screened for their cytotoxic activity in six cell lines. As compared with the positive control, some compounds showed better anti-proliferative activities while having much weaker effect on the growth of normal cells. Among them, ring-A fused pyrazoline of PD (1j) displayed impressive cytotoxic activity with IC50 9.62 ± 1.34, 11.65 ± 1.71, and 13.45 ± 1.60 μM against A549, HeLa and 8901 cell lines, respectively. Additionally, compound 2f exhibited the most potent activity with an IC50 value of 8.93 ± 1.11 μM against cell line A549. Therefore, our results indicated that 1j and 2f can be promising lead candidates for further studies.

Synthesis, characterization and cytotoxic activity evaluation of ginsengdiol oxidation and nitrogen hybrid derivatives.

Synth. einiger sterin- und triterpen-glykoside

The synthesis of lanosterol,β-sitosterol, cholesterol, and panaxadiolβ-glycosides was accomplished. The feasibility of glycosylating diatomic triterpenic alcohols was demonstrated with panaxadiol. The glycosylation ofβ-sitosterol and cholesterol is accompanied by the formation of di-β-sitosterol and dicholesterol ethers. Synthetic panaxadiol monoside possesses a higher physiological activity than the original panaxadiol.

The synthesis of some sterol and triterpenic glycosides

Preparations from the Far Eastern plant Eleuterococcus senticosus Maxim, which belongs to the family of Araliaceae, have achieved widespread use in medicine as agents that increase the general nonspecific resistance of the organism [i, 2]. Eleuterococcus preparations are widely used in the same role in animal husbandry [3]. In medicine an alcohol extract from Eleuterococc~s roots (ethanol content 33%) is used. The extract from the roots contains glycosides, with which the basic biological activity of E~euterococcus is associated, along with ascorbic acid, ~-carotene, vitamin E, chlorogenic acid, and other compounds [4-9]. Ten different glycosides, which have received the general name of \"eleuterosides,\" have been detected in an extract of Eleuterococcus roots the main components among them are eleuteroside A (daucosterol), B (syringing, BI (isofraxidin-7-O-a-L-glycoside), D (syringaresinol-di-e-B-Dglycoside), E (a conformer of D), and F [4-9]. In a methanol extract the ratio A:B:BI:C:D:E:F is equal to 8:30:10:12:24:2:1 [2]. According to other data [4-9], the above-mentioned substances are contained in an extract from the roots in a ratio 2:10:(traces):8:16:2:l.

Investigation of the pharmacokinetics and mechanism of action of glycosides ofEleuterococcus. I. Introduction of tritium into eleuteroside B. kinetics of its accumulation and elimination from the animal organism

Pharmacokinetics and mechanism of action of eleutherococcus glycosides. V. Metabolism and binding kinetics to serum components

In an investigation of the subcellular localization of [3H]eleutheroside B in various rat organs, a predominant accumulation of labeled eleutheroside in the microsomal fraction was detected [2], which seems natural, since the enzyme systems of protection of the organism from exogenous low-molecular-weight substances are concentrated precisely in the membranes of the endoplasmic reticulum (especially in the liver). This group of enzymes has been named cytochromes P-450, which, like hydroxylating enzymes in general, break down various foreign compounds, and also limit the time in which various narcotics can retain their activity. Cytochromes P-450 are inducible enzymes; this means that the amount of the enzyme may be increased by a factor of 25 when one of the foreign compounds is introduced [i].

I. V. Dardymov

Papers

The synthesis of some sterol and triterpenic glycosides

Investigation of the pharmacokinetics and mechanism of action of glycosides ofEleuterococcus. I. Introduction of tritium into eleuteroside B. kinetics of its accumulation and elimination from the animal organism

Pharmacokinetics and mechanism of action of eleutherococcus glycosides. V. Metabolism and binding kinetics to serum components

Pharmacokinetics and mechanism of action ofEleutherococcus glycosides. VII. Influence of an extract and individual glycosides on protein biosynthesis

Influence of extract ofEleutherococcus and eleutherosides A, B, C, D + E on release and metabolism of arachidonic acid