- Synthesis and evaluation of asiatic acid derivatives as anti-fibrotic agents: Structure/activity studies
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Fibrotic diseases are characterized by the over-accumulation of fibrous components in the extracellular matrix and the liver, which can lead to liver cirrhosis. Current treatment options cannot reverse or halt liver fibrosis, motivating a search for newer treatment options. Previously, we showed that asiaticoside, a bioactive triterpene glycoside from Centella asiatica, has anti-fibrotic properties. Here, the aglycone asiatic acid was chemically modified, and these derivatives were evaluated for their potential as anti-fibrotic agents. The data obtained from in vivo testing of these compounds in a rodent CCl4-induced liver injury model are discussed. The information obtained from these studies may be useful in the design of novel anti-fibrotic agents.
- Li, Yong,Yang, Fang,Yuan, Mingxing,Jiang, Lijuan,Yuan, Li,Zhang, Xiaowei,Li, Ying,Dong, Lin,Bao, Xu,Yin, Shufan
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- ALEANANE AND URSANE GLYCOSIDES FROM SCHEFFLERA OCTOPHYLLA
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Twelve triterpene glycosides were isolated from the bark of Schefflera octophylla of Vietnamese origin.Three of them were identified as asiaticoside, cauloside D and 3α-hydroxyurs-12-ene-23,28-dioic acid 28-O-α-L-rhamnopyranosyl(1-->4)-β-D-glucopyranosyl(1-->6)-β-D-glucopyranoside.The structures of nine new glycosides were elucidated by chemical and spectroscopic evidence.Including the known compounds, the 12 glycosides consisted of six pairs of corresponding ursene and oleanene glycosides and all of them had the same triose moiety at the C-28 position.The names scheffurosides A-F and scheffoleosides B-F were proposed for corresponding pairs of ursene and oleanene glycosides, respectively. - Key words: Schefflera octophylla; Araliaceae; triterpene glycoside; oleanane; ursane; asiaticoside; cauloside D; scheffoleoside A, B, E, F; scheffursoside B, C, D, E, F.
- Maeda, Chizuko,Ohtani, Kazuhiro,Kasai, Ryoji,Yamasaki, Kazuo,Duc, Nguyen Minh,et al.
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- Biocatalyzed generation of molecular diversity: Selective modification of the saponin asiaticoside
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An array of different derivatives of the complex ursane-type triterpene glycoside asiaticoside (1), a saponin component isolated from the perennial herb Centella asiatica, was generated by exploiting the stereo-, regio- and site-selectivity of four groups of enzymes (glycosidases, glycosyltransferases, lipases and laccases). A library of extracellular α-L-rhamnosidases (31 different items) was obtained by screening 16 different fungal strains under different cultivation conditions, and several of these preparations catalyzed the derhamnosylation of asiaticoside. Specifically, the enzymes produced by Fusarium oxysporum were selected for the synthesis of derhamno-degluco- asiaticoside (2) and also of derhamno-asiaticoside (3), by in situ glucose-inhibition of contaminating β-D-glucosidases. β-1,4- Galactosyltransferase from bovine milk was subsequently used for the galactosylation of the two asiaticoside derivatives 2 and 3, using 20% v/v DMSO as a cosolvent in order to increase substrate solubility. Finally, new acylated and oxidized derivatives of asiaticoside were also prepared by exploiting the lipase from Candida antarctica (Novozym 435) and the laccase from Trametes pubescens, respectively.
- Monti, Daniela,Candido, Andrea,Cruz Silva, M. Manuel,Kren, Vladimir,Riva, Sergio,Danieli, Bruno
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- Synthesis, antiproliferative and apoptosis-inducing effects of novel asiatic acid derivatives containing α-aminophosphonates
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A series of novel asiatic acid (AA) derivatives containing α-aminophosphonate were designed and synthesized as antitumor agents. In vitro antitumor activities of these compounds against five cancer cell lines (A549, Hct-116, T24, Spca-2 and SK-OV-3 cell) and a normal cell line (HUVEC cell) were evaluated, employing standard MTT assay. Antitumor activities screening result indicated that many target compounds displayed moderate to high levels of antitumor activities compared with AA, 5-fluorouracil (5-FU) and cisplatin, and exhibited much lower cytotoxicity against normal cell than 5-FU and cisplatin. In addition, the mechanism of representative compound 3d was preliminarily investigated by AO/EB staining, Hoechst 33258 staining, JC-1 mitochondrial membrane potential staining, flow cytometry and western blot. Compound 3d inducing apoptosis involved intracellular Ca2+ production, the loss of mitochondrial membrane potential and intracellular reactive oxygen species (ROS) production. Western blot analysis also demonstrated that compound 3d treatment triggered the mitochondrial apoptotic pathway, indicating by changing Bax/Bcl-2 ratios, cytochrome c release, and caspase-9 activation. Moreover, the cell cycle analysis showed that compound 3d may confine T24 cells in G1/S phase mainly through the p53-dependent pathway. Together, these results implied a critical role of ROS, caspase-9 and p53 in compound 3d-inducing G1/S arrest and apoptosis of T24 cells.
- Huang, Ri-Zhen,Wang, Cai-Yi,Li, Jian-Fei,Yao, Gui-Yang,Pan, Ying-Ming,Ye, Man-Yi,Wang, Heng-Shan,Zhang, Ye
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- Method for preparing asiatic acid by hydrolyzing asiaticoside
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The invention discloses a method for preparing asiatic acid by hydrolyzing asiaticoside. The method comprises the following steps: 1) mixing asiaticoside, lauryl sodium sulfate and NaOH, adding water for dissolution, and hydrolyzing at normal temperature for 10-15 minutes; 2) regulating the pH value of the hydrolysate to 2-5, standing, filtering, and collecting the precipitate; and 3) dissolving the precipitate in ethanol, filtering, adding water to the filtrate, crystallizing, filtering to obtain the crystal, and drying to obtain the finished product. The method can quickly cut off glycosidic bonds under the conditions of normal temperature and pressure, has the advantages of mild hydrolytic process and thorough hydrolysis, and can not generate configurative changes of asiatic acid.
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Paragraph 0017-0032
(2017/08/27)
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- An Asiatic acid derivatives
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The invention provides derivatives based on an asiatic acid structure for modification. Pharmacological activity experiments prove that the compounds provided by the invention (in particular to 5a, 5b, 5d and 5f) have relatively good antifibrotic activity; and furthermore, in comparison with asiatic acid, the compounds disclosed by the invention have the advantages that the lipid solubility is improved, and new choices are provided for clinical medicines.
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Paragraph 0025-0027
(2017/02/24)
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- Design, synthesis, and biofunctional evaluation of novel pentacyclic triterpenes bearing O-[4-(1-piperazinyl)-4-oxo-butyryl moiety as antiproliferative agents
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A series of pentacyclic triterpenoids derivatives bearing O-[4-(1-piperazinyl)-4-oxo-butyryl moiety has been synthesized and investigated for their potential antiproliferative activities. Pentacyclic triterpenoids derivative compounds were synthesized by a four or six step synthetic procedure. The activity studies were evaluated using Cell Counting Kit-8 method, and Western blotting analysis on A549 cells, MCF-7 cells and Hela cells. Compounds methyl 3-O-[4-(1-piperazinyl)-4-oxo-butyryl]olean-12-ene-28-oate (OA-4) and compound 2-O-[4-(1-piperazinyl)-4-oxo-butyryl]-3,23-dihydroxyurs-12-ene-28-oate (AA-5) were found to be promising antiproliferative agents. These compounds show potentiality for further optimization as antitumor drugs.
- Zhao, Chun-Hui,Zhang, Cui-Li,Shi, Jin-Jie,Hou, Xi-Yan,Feng, Bin,Zhao, Long-Xuan
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p. 4500 - 4504
(2015/10/12)
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- Antiproliferative, cell-cycle dysregulation effects of novel asiatic acid derivatives on human non-small cell lung cancer cells
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Asiatic acid (AA) is a pentacyclic triterpene in Centella asiatica known to inhibit proliferation and induce apoptosis in several tumor cell lines. In the current study, we synthesized five AA derivatives and examined their inhibitory activities on growth in non-small cell lung cancer cell lines, A549 and PC9/G. Four derivatives were found to have stronger cell growth inhibitory activity than AA. Among them, compound A-3 showed the most significant antiproliferative effects on tumor. Growth of A549 and PC9/G cells was inhibited by A-3 in a dose- and time-dependent manner. To determine the cellular gene expression changes in A549 and PC9/G cells treated with A-3, Affymetrix GeneChip Human Genome U133 Plus 2.0 Array were used to screen transcriptome differences. Expression levels of 1121 genes in A549 and 1873 genes in PC9/G were significantly altered upon treatment with 10 μM A-3 after 48 h, with 357 overlapping genes. The signaling pathways molecules involved in the antiproliferative and cell cycle dysregulation effects of A-3 identified using microarray were further validated via Western blot analyses. The results collectively indicate that A-3 induces inhibition of cell proliferation via downregulation of the Ras/Raf/MEK/ERK pathway and cell cycle arrest at G1/S and G2/M.
- Wang, Liang,Xu, Jie,Zhao, Chunhui,Zhao, Longxuan,Feng, Bin
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p. 1015 - 1023
(2013/11/19)
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- THERAPEUTIC FORMULATIONS BASED ON ASIATIC ACID AND SELECTED SALTS THEREOF
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A highly pure asiaticoside and a pharmaceutical grade asiatic acid can be prepared, along with salts of asiatic acid, for use in formulating therapeutic compositions that are suitable for treating arthritis, psoriasis and other inflammatory diseases, as well as pulmonary fibrosis, diabetic nephropathy, and other fibrotic diseases.
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Page/Page column 6-7
(2009/09/04)
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