A series of echinocystic acid （EA） 28-COOH derivatives was synthesized, and their anti-HCV entry activity was evaluated by HCVpp and VSVpp entry assay. It was found that some of them showed moderate anti-HCV entry a...A series of echinocystic acid （EA） 28-COOH derivatives was synthesized, and their anti-HCV entry activity was evaluated by HCVpp and VSVpp entry assay. It was found that some of them showed moderate anti-HCV entry activity, especially compound 12, and these modifications also removed the undesired hemolytic effect.展开更多
Oleanolic acid(OA) and echinocystic acid(EA), two naturally occurring pentacyclic oleanane triterpenes,are gaining increasing attention due to their promising pharmacological activities. Conjugation with amphiphilic ...Oleanolic acid(OA) and echinocystic acid(EA), two naturally occurring pentacyclic oleanane triterpenes,are gaining increasing attention due to their promising pharmacological activities. Conjugation with amphiphilic α(β)-cyclodextrin(CD) via "click chemistry" can improve their solubility and anti-HCV entry potency. In the present work,four water-soluble β-CD-pentacyclic triterpene conjugates were designed and synthesized, in which OA and EA was coupled to one of the primary hydroxyl groups of β-CD via ester and amide bonds. The structures of the conjugates were unambiguously determined by ~1H NMR, ^(13)C NMR and HRMS or MALDI-TOF-MS. All the conjugates showed lower hydrophobicity(AlogP) than their parent compounds and no significant cytotoxicity was found to HL-60, A549, Hela and Bel-7402 cells at concentrations up to 10 μmol/L. Further anti-HCV entry activity and mechanism studies are under way in our laboratory.展开更多
A series of triterpene dimers bearing different scaffold were designed and synthesized via CuAAC reaction. Their anti-HCV entry activities were evaluated by HCVpp and VSVpp entry assays. It was found that echinocystic...A series of triterpene dimers bearing different scaffold were designed and synthesized via CuAAC reaction. Their anti-HCV entry activities were evaluated by HCVpp and VSVpp entry assays. It was found that echinocystic acid （EA） and its dimer were still necessary for maintaining anti-HCV entry activity, and replacement of EA by other triterpenes might significantly decrease its anti-viral activities. Using a linker bearing a piperazine group, compound 14 dramatically increased its potency with IC50 at 2.87 nmol/L. In addition, the undesired hemolytic effect of all these compounds was removed.展开更多
基金supported by the National Natural Science Foundation of China (Nos. 81373271 and 81361168002)OpenFund Program of the State Key Laboratory of Natural and Biomimetic Drugs (No. K20150214)Yunnan Basic Research Project (No. 14051789)
文摘A series of echinocystic acid （EA） 28-COOH derivatives was synthesized, and their anti-HCV entry activity was evaluated by HCVpp and VSVpp entry assay. It was found that some of them showed moderate anti-HCV entry activity, especially compound 12, and these modifications also removed the undesired hemolytic effect.
基金supported by the National Natural Science Foundation of China (Nos. 81573269, 21572015, 21877007, 91753202 and 21702007)and the open funding of the State Key Laboratory of Phytochemistry and Plant Resources in West China
文摘Oleanolic acid(OA) and echinocystic acid(EA), two naturally occurring pentacyclic oleanane triterpenes,are gaining increasing attention due to their promising pharmacological activities. Conjugation with amphiphilic α(β)-cyclodextrin(CD) via "click chemistry" can improve their solubility and anti-HCV entry potency. In the present work,four water-soluble β-CD-pentacyclic triterpene conjugates were designed and synthesized, in which OA and EA was coupled to one of the primary hydroxyl groups of β-CD via ester and amide bonds. The structures of the conjugates were unambiguously determined by ~1H NMR, ^(13)C NMR and HRMS or MALDI-TOF-MS. All the conjugates showed lower hydrophobicity(AlogP) than their parent compounds and no significant cytotoxicity was found to HL-60, A549, Hela and Bel-7402 cells at concentrations up to 10 μmol/L. Further anti-HCV entry activity and mechanism studies are under way in our laboratory.
基金Acknowledgement This work was supported by the National Natural Science Foundation of China （No. 81560560）, Open-Fund Program of the State Key Laboratory of Natural and Biomimetic Drugs （No. K20160209） and Yunnan Basic Research Project （No. 14051789）.
文摘A series of triterpene dimers bearing different scaffold were designed and synthesized via CuAAC reaction. Their anti-HCV entry activities were evaluated by HCVpp and VSVpp entry assays. It was found that echinocystic acid （EA） and its dimer were still necessary for maintaining anti-HCV entry activity, and replacement of EA by other triterpenes might significantly decrease its anti-viral activities. Using a linker bearing a piperazine group, compound 14 dramatically increased its potency with IC50 at 2.87 nmol/L. In addition, the undesired hemolytic effect of all these compounds was removed.
