- Synthesis and biological evaluation of novel aniline-derived asiatic acid derivatives as potential anticancer agents
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Asiatic acid (AA) derivatives 4 and 5 modified at the C-11 and C-28 positions were designed and synthesized, their structures were confirmed using HRMS, 1H NMR and 13C NMR. In vitro antitumor activities of all compounds against MGC-8
- Li, Jian-Fei,Huang, Ri-Zhen,Yao, Gui-Yang,Ye, Man-Yi,Wang, Heng-Shan,Pan, Ying-Ming,Xiao, Jing-Teng
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- Asiaticoside mimetics as wound healing agent
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Novel asiaticoside mimetics simplified the sugar moiety by alkoxyalkyl groups were synthesized, and tested their wound healing effects by tensile strength measurement.
- Shim, Pil-Jong,Park, Jae-Ho,Chang, Min-Sun,Lim, Min-Jung,Kim, Do-Ha,Jung, Young Hoon,Jew, Sang-Sup,Park, Eun Hee,Kim, Hee-Doo
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- Synthesis of asiatic acid derivatives and their cytotoxic activity
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Twenty-eight compounds, including 24 new (4–22, 25–26, and 28–30) and four known (2, 23, 24, and 27) have been synthesized starting from asiatic acid (1), which was isolated from Centella asiatica. The preparation procedure included the acetylation, hydrolyzation on the 2-, 3-, 23-, and the side chain hydroxyl, amino groups, as well as the amidation of the 28-carboxylic group. All the synthesized derivatives were structurally confirmed by 1H, 13C NMR, and MS spectra. Besides, they were evaluated for their cytotoxicity against three cancer cell lines: KB (human carcinoma in the mouth), HepG2 (human hepatocellular carcinoma), and SK-LU-1 (human lung carcinoma). Eleven of the tested compounds, including nine newly synthesized and two known ones showed very strong activity against three tested cell lines with the IC50 values ranging from 0.67 to 37.39 μM. Three compounds showed good activity against KB and HepG2 cell lines with the IC50 values ranging from 1.95 to 32.12 μM. The activity against the KB and HepG2 cell lines was in general higher than that against the SK-LU-1 cell line. The acetylation of the hydroxyl groups in the A-ring and the OH or NH groups in the amide side chains strongly enhanced the activity of the compounds. In addition, five potent compounds (9, 12, and 15–17) were also evaluated for apoptosis-inducing activities. The ratio of apoptosis and necrotic cells increased when lung cancer cells were treated with these compounds. On the other hand, compound 9 increased caspase 3 activities (P 0.05). Thus, these compounds induced lung cancer cell death by apoptosis and necrosis.
- Tran Van, Loc,Vo Thi, Quynh Nhu,Tran Van, Chien,Tran Thi, Phuong Thao,Pham Thi, Ninh,Nguyen Tuan, Thanh,Le Thi, Thu Ha,Nguyen Thi, Nga,Do Thi, Thao,Tran Van, Sung
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- Synthesis and antitumor activity evaluation of asiatic acid derivatives as survivin inhibitor
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A series of asiatic acid derivatives were synthesized and their cytotoxicities in vitro against two cancer cell lines (HepG2 and SGC7901) were evaluated by MTT assay. The results showed that compounds I2, I6, and II6 have
- Meng, Yan-Qiu,Cui, Hua-Bo,Li, Lei,Zhang, Wei-Chen,Pan, Hong-Shuang,Yu, Ting-Ting,Li, Wei
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- Design, synthesis, and biological evaluation of novel asiatic acid derivatives as potential anticancer agents
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A series of new asiatic acid derivatives modified in the A-ring and at C-28 were synthesized and their antiproliferative activity was evaluated against HT-29 and HeLa cell lines. Most of the derivatives tested here exhibited improved antiproliferative activity compared with asiatic acid. Among them, the best compounds, 7 and 8, were further evaluated against additional cancer cell lines (MCF-7, Jurkat, and PC-3 cells) and a nontumoral cell line (BJ). The most active compound, 7, exhibited IC50 values ranging from 1.62 μM in HeLa cells to 9.93 μM in MCF-7 cells. Further studies revealed that compound 7 arrested the cell cycle at the G0/G1 phase and induced caspase-dependent apoptosis in HeLa cells. Furthermore, this compound showed selectivity toward cancer cells, and a synergistic effect was observed after simultaneous treatment of HeLa cells with compound 7 and cisplatin. Collectively, our results suggest that compound 7 may be useful for the development of new anticancer therapies; thus, additional preclinical studies are warranted.
- Gon?alves, Bruno M. F.,Salvador, Jorge A. R.,Santos, Diana S. M.,Marín, Silvia,Cascante, Marta
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- An Investigation of the Differential Effects of Ursane Triterpenoids from Centella asiatica, and Their Semisynthetic Analogues, on GABAA Receptors
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The ursane triterpenoids, asiatic acid 1 and madecassic acid 2, are the major pharmacological constituents of Centella asiatica, commonly known as Gotu Kola, which is used traditionally for the treatment of anxiety and for the improvement of cognition and memory. Using the two-electrode voltage-clamp technique, these triterpenes, and some semisynthetic derivatives, were found to exhibit selective negative modulation of different subtypes of the GABAA receptor expressed in Xenopus laevis oocytes. Despite differing by only one hydroxyl group, asiatic acid 1 was found to be a negative modulator of the GABA-induced current at α1β2γ2L, α2β2γ2L and α5β3γ2L GABAA receptors, while madecassic acid 2 was not. Asiatic acid 1 exhibited the greatest effect at α1β2γ2L (IC50 37.05 μm), followed by α5β3γ2L (IC50 64.05 μm) then α2β2γ2L (IC50 427.2 μm) receptors. Conversion of the carboxylic acid group of asiatic acid 1 to a carboxamide group (2α,3β,23-trihydroxy-urs-12-en-28-amide 5) resulted in enhanced inhibition at both the α1β2γ2L (IC50 14.07 μm) and α2β2γ2L receptor subtypes (IC50 28.41 μm). The results of this study, and the involvement of α5-containing GABAA receptors in cognition and memory, suggest that asiatic acid 1 may be a lead compound for the enhancement of cognition and memory.
- Hamid, Kaiser,Ng, Irene,Tallapragada, Vikram J.,Váradi, Linda,Hibbs, David E.,Hanrahan, Jane,Groundwater, Paul W.
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- Synthesis and discovery of asiatic acid based 1,2,3-triazole derivatives as antitumor agents blocking NF-κB activation and cell migration
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A series of asiatic acid (AA) based 1,2,3-triazole derivatives were designed, synthesized and subjected to a cell-based NF-κB inhibition screening assay. Among the tested compounds, compound 6k displayed impressive NF-κB inhibitory activity with an ICsub
- Huang, Ri-Zhen,Liang, Gui-Bin,Li, Mei-Shan,Fang, Yi-Lin,Zhao, Shi-Feng,Zhou, Mei-Mei,Liao, Zhi-Xin,Sun, Jing,Wang, Heng-Shan
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p. 584 - 597
(2019/04/30)
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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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p. 62890 - 62906
(2016/07/16)
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- Selective killing of cancer cells with triterpenoic acid amides - The substantial role of an aromatic moiety alignment
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2,3-Di-O-acetyl-triterpenoic acid derived amides possessing a (2β, 3β) configuration in ring A and two acetyl groups were previously shown to possess high cytotoxicity for human tumor cell lines but to exhibit low cytotoxicity for non-malignant mouse fibroblasts. In this study, augustic acid (1) and 2-epi-corosolic acid (2) were chosen as starting points for the synthesis of analogs. While augustic acid derived 3-quinolinyl amide 9 gave low EC50values in SRB assays but was cytotoxic for all lines, the isomeric 4-isoquinolinyl amide 21 was very cytotoxic for the tumor cell lines but significantly less cytotoxic for the mouse fibroblasts NIH 3T3. In addition, a triacetylated 4-isoquinolinyl derivative of asiatic acid (28) gave EC50?=?80?nM (for A2780 ovarian cancer cells). As shown by additional experiments (acridine orange/propidium iodide staining, fluorescence spectroscopy and cell cycle investigations) these compounds act mainly by apoptosis.
- Sommerwerk, Sven,Heller, Lucie,Kuhfs, Julia,Csuk, René
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p. 452 - 464
(2016/07/15)
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- Synthesis, anti-tumor and anti-angiogenic activity evaluations of asiatic acid amino acid derivatives
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Fifteen semi-synthetic derivatives of asiatic acid (AA) have been synthesized and evaluated for their biological activities. The successful modification of these compounds at the C-2, C-3, C-23 and C-28 positions was confirmed using NMR, MS and IR spectra. Further, their anti-tumor effects were evaluated in vitro using different cancer cell lines (HeLa, HepG2, B16F10, SGC7901, A549, MCF7 and PC3), while their anti-angiogenic activities were evaluated in vivo using a larval zebrafish model. Among the derivatives, compounds 4-10 showed more potent cytotoxic and anti-angiogenic effects than AA, while compounds 11-17 had significantly less effects. The new derivative 10 was also included in finished formulations to evaluate its stability using HPLC due to its potential topical use. The derivative 10 had markedly better anti-tumor activities than both AA and other derivatives, with similar stability as its parent compound AA.
- Jing, Yue,Wang, Gang,Ge, Ying,Xu, Minjie,Gong, Zhunan
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p. 7309 - 7324
(2015/05/13)
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- Synthesis and antitumor activity evaluation of new asiatic acid derivatives
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Twelve novel asiatic acid (AA) derivatives were designed and synthesized. Their structures were confirmed using NMR, MS, and IR spectra. Their in vitro cytotoxicities on various cancer cell lines (HeLa, HepG2, BGC-823, and SKOV3) were evaluated by the 3-(
- Meng, Yan-Qiu,Li, Yun-Yun,Li, Feng-Qing,Song, Yan-Ling,Wang, Hai-Feng,Chen, Hong,Cao, Bo
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p. 844 - 855,12
(2020/08/24)
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- Synthesis and biological evaluation of asiatic acid derivatives as inhibitors of glycogen phosphorylases
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Twenty-four asiatic acid derivatives have been synthesized and biologically evaluated as inhibitors of glycogen phosphorylase (GP). Within this series of compounds, asiatic acid benzyl ester (23; IC50=3.8 μm) exhibited more potent activity than
- Zhang, Liying,Chen, Jun,Gong, Yanchun,Liu, Jun,Zhang, Luyong,Hua, Weiyi,Sun, Hongbin
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experimental part
p. 864 - 874
(2010/04/23)
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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 14
(2009/09/04)
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- Structure-activity relationship study of asiatic acid derivatives against beta amyloid (Aβ)-induced neurotoxicity
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8 Semi-synthetic derivatives of asiatic acid were prepared and their protective effect against Aβ-induced neurotoxicity was evaluated. Among them, asiatic acid (2), and 4, 16 showed 97, 92 and 87% of protective effect, respectively.
- Jew, Sang-Sup,Yoo, Chi-Hyoung,Lim, Doo-Yeon,Kim, Heeman,Mook-Jung, Inhee,Whan Jung, Min,Choi, Heesung,Jung, Young-Hoon,Kim, Heedoo,Park, Hyeung-Geun
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p. 119 - 121
(2007/10/03)
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