Studies On Structural Modification Of Dammarane Type Ginsengenin And Their Antitumor Activity

Ginseng, which is the root of Panax ginseng C.A.Meyer, is a well-known Chinese andforeign valuable herbal medicine. Dammarane type ginsenosides and their aglycone are themajor anti-cancer components of ginseng, and considered to be perspective antitumor drugcandidates. Ginsenoside possesses the advantage of low toxicity, high efficiency, targeting.Taken ginsenoside as the lead compound and had its structure modified can contribute a newway for the development of new antitumor drugs.In this paper, based on the previous work of our group, we designed and synthesized20(R)-panaxadiol and20(R)-panaxatriol derivatives, which achieved from acid hydrolysateof the total ginsenosides of Panax ginseng C. A. Meyer (Araliaceae). Our structuremodification was mainly objective to the side chain of20(R)-panaxadiol(compound1) and20(R)-panaxatriol (compound2) with Acetyl chloride; the method operation was moresimple, the product yield was higher, the by-product was less and the reaction regent wasmuch less toxic than previously experiment. Here we got six dammarane type ginsenosidederivatives,dammar-(Z)-20(22)-ene-3,6-diacetyl-25-hydroxy (compound3),.dammar-(E)-20(22)-ene-3,6-diacetyl-25-hydroxy (compound4),20(R)-3-acetyl-panaxadiol (compound5),dammar-(Z)-20(22)-ene-3,6,12-triacetyl-25-hydroxy(compound6) dammar-(E)-20(22)-ene-3,6,12-triacetyl-25-hydroxy (compound7) and20(R)-3-acetyl-panaxatriol (compound8),respectively. Of which compound3and compound4, compound6and compound7werecomplementation heterogeneous, and were the new compounds that have not seen in theliteratures so far.We also studied the antitumor activity of the structure modified products in vitro byMTT method to exam the inhibitory effect on human laryngeal cancer HP-2cellsproliferation. Preliminary result showed that the structure modified products had thedifferent degree on damaging effect to the cancer HP-2cells. And (R)-panaxatriol modifiedderivatives performaned better anti-tumor activity than20(R)-panaxadiol modifiedderivatives; Furthermore, the E configuration product exhibited stonger anti-tumor activity than the Z configuration product.In this paper, we modified the C-17side chain of dammarane type ginsengenin20(R)-panaxadiol and20(R)-panaxatriol, and achieved the oxygen hexahydroxy ring-openderivatives, which reduced the space steric hindrance of C-12. We also preliminarily studiedtheir derivatives antitumor activity. It provides the theory reference to study further structuralmodification of ginsenosides and gain better active antitumor candidate molecules.