Synthesis And Screening Of Ardipusilloside Ⅰ Derivatives

Pentacyclic triterpene saponins and their sapogenins, naturally occuring in alarge variety of plants, have attracted much attention due to their multi-facetedbiological activities including significant antitcancer and antiviral properties.Ardipusilloside Ⅰ, a pentacyclic triterpenoid saponin isolated from Ardisiapusilla A. DC, has been shown to have inhibitory effect on the growth of a varietyof cancer cells and immunoregulatory effect on human immune responses.Cylamiretin A is the primary sapoginin of Ardipusilloside Ⅰand Cyclamiretin D isthe secondary sapoginin. So far no research has been reported on the anticanceractivities of Cylamiretin A and Cyclamiretin D. Chemical modification ofArdipusilloside Ⅰand its sapoginins and biological screening of their derivativesare of great significance in clarifying their structure-activity relationship anddeveloping better saponin-type anticancer drugs.This work mainly consists of the following four parts:1. Six Ardipusilloside Ⅰderivatives were synthesized by oxidation orreduction of the C-30formyl group of the saponin, or condensation of the C-30formyl group with various amino compounds such as thiosemicarbazide,hydroxysemicarbazide, and methyl hydrazinecarbdithiolate.2. Cylamiretin A and Cyclamiretin D were obtained by hydrolysis ofArdipusilloside Ⅰ under various conditions. It has been shown that acid-catalyzedhomogeneous hydrolysis of Ardipusilloside Ⅰ mainly gave Cyclamiretin D whilebiphasic hydrolysis of Ardipusilloside Ⅰ mainly gave Cylamiretin A.3. Five C-3ester derivatives of Cylamiretin A were obtained by treatment ofCylamiretin A with various organic acid or acid anhydride. Thirteen CyclamiretinD derivatives were prepared by oxidation or esterification of Cyclamiretin D, orcondensation of Cyclamiretin D with animo compounds such as thiosemicarbazide,1-aminopiperidine and methyl hydrazinecarbdithiolate.4. Anticancer anctivities of Ardipusilloside Ⅰderivatives against nine cancercell lines were evaluated by MTT assay. The results showed that oxidation orreduction of the C-30formyl group of Ardipusilloside Ⅰdrastically decreased itsinhibition of cancer cell proliferation while condensation of the C-30formyl group with thiosemicarbazide greatly enhanced its anticancer effect.