- Polymethoxyflavones from Gardenia oudiepe (Rubiaceae) induce cytoskeleton disruption-mediated apoptosis and sensitize BRAF-mutated melanoma cells to chemotherapy
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A series of 10 natural and semisynthetic flavonoids (1 to 10) were obtained from Gardenia oudiepe (Rubiaceae), an endemic plant from New Caledonia. Most of them were polymethoxylated flavones (PMFs) of rare occurrence. After a cell viability screening test, PMFs 2 and 3 showed significant cytotoxic activity against A2058 human melanoma cells (IC50 = 3.92 and 8.18 μM, respectively) and were selected for in-depth pharmacological assays. Both compounds inhibited cell migration and induced apoptosis and cell cycle arrest after 72h of treatment. Immunofluorescence assays indicated that these outcomes were possibly related to the induction of cytoskeleton disruption associated to actin and tubulin depolymerization. These data were confirmed by molecular docking studies, which showed a good interaction between PMFs 2 and 3 and tubulin, particularly at the colchicine binding site. As A2058 are considered as chemoresistant to conventional chemotherapy, compounds 2 and 3 (?IC50) were associated to clinically-used antimelanoma drugs (vemurafenib and dacarbazine) and combined therapies efficacy was assessed by the MTT assay. PMFs 2 restored the sensitivity of A2058 cells to dacarbazine treatment (IC50 = 49.38 μM vs. >100 μM). Taken together, these data suggest that PMFs from G. oudiepe could be potential leaders for the design of new antimelanoma drugs.
- Beaugeard, Laureen,Beserra de Alencar Filho, Edilson,Guedes da Silva Almeida, Jackson Roberto,Michel, Sylvie,Picot, Laurent,Gon?alves de Oliveira-Júnior, Raimundo,Grougnet, Rapha?l,Marcoult-Fréville, Nolwenn,Prunier, Grégoire,Quintans-Júnior, Lucindo José,Sim?es Mour?o, Eduard David
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- Discovery of a Prenylated Flavonol Derivative as a Pin1 Inhibitor to Suppress Hepatocellular Carcinoma by Modulating MicroRNA Biogenesis
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Peptidyl-prolyl cis-trans isomerase Pin1 plays a crucial role in the development of human cancers. Recently, we have disclosed that Pin1 regulates the biogenesis of miRNA, which is aberrantly expressed in HCC and promotes HCC progression, indicating the therapeutic role of Pin1 in HCC therapy. Here, 7-(benzyloxy)-3,5-dihydroxy-2-(4-methoxyphenyl)-8-(3-methylbut-2-en-1-yl)-4H-chromen-4-one (AF-39) was identified as a novel Pin1 inhibitor. Biochemical tests indicate that AF-39 potently inhibits Pin1 activity with an IC50 values of 1.008 μm, and also displays high selectivity for Pin1 among peptidyl prolyl isomerases. Furthermore, AF-39 significantly suppresses cell proliferation of HCC cells in a dose- and time-dependent manner. Mechanistically, AF-39 regulates the subcellular distribution of XPO5 and increases miRNAs biogenesis in HCC cells. This work provides a promising lead compound for HCC treatment, highlighting the therapeutic potential of miRNA-based therapy against human cancer.
- Zheng, Yuanyuan,Pu, Wenchen,Li, Jiao,Shen, Xianyan,Zhou, Qiang,Fan, Xin,Yang, Sheng-Yong,Yu, Yamei,Chen, Qiang,Wang, Chun,Wu, Xin,Peng, Yong
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supporting information
p. 130 - 134
(2018/11/30)
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- ACYLATED CATECHIN POLYPHENOLS AND METHODS OF THEIR USE FOR THE TREATMENT OF CANCER
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Disclosed herein are acylated active agents and methods of their use, e.g., for modulating a cancer marker or for treating cancer.
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Page/Page column 44
(2019/12/28)
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- ACTIVE AGENTS AND METHODS OF THEIR USE FOR THE TREATMENT OF METABOLIC DISORDERS AND NONALCOHOLIC FATTY LIVER DISEASE
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Disclosed herein are active agents, compositions containing them, unit dosage forms containing them, and methods of their use, e.g., for treating a metabolic disorder or nonalcoholic fatty liver disease or for modulating a metabolic marker or nonalcoholic fatty liver disease marker.
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Page/Page column 67; 75
(2019/12/28)
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- ACYLATED ACTIVE AGENTS AND METHODS OF THEIR USE FOR THE TREATMENT OF AUTOIMMUNE DISORDERS
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Disclosed herein are acylated active agents (e.g., acylated catechin polyphenols, acylated carotenoids, acylated mesalamines, acylated sugars, acylated shikimic acids, acylated ellagic acid, acylated ellagic acid analogue, and acylated hydroxybenzoic acids), active agent combinations (e.g., with a second agent that is a fatty acid) and methods of their use, e.g., for modulating an autoimmunity marker or for treating an autoimmune disorder.
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Page/Page column 57; 135-136
(2019/12/28)
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- Design, synthesis and molecular docking analysis of flavonoid derivatives as potential telomerase inhibitors
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Based on the structural scaffolds of natural products, two series of flavonoid derivatives, for a total of twelve compounds, were designed and synthesized as potential human telomerase inhibitors. Using a modified TRAP-PCR assay, compound 5c exhibited the most potent inhibitory activity against human telomerase with an IC50 value of less than 50 μM. In vitro, the results demonstrated that compound 5c had potent anticancer activity against five classes of tumor cell lines. The molecular docking and molecular dynamics analyses binding to the human telomerase holoenzyme were performed to elucidate the binding mode of active compound 5c. This finding helps the rational design of more potent telomerase inhibitors based on the structural scaffolds of natural products.
- Cheng, Mao-Sheng,Fan, Zhan-Fang,Fu, Ya,Ho, Sai-Tim,Hu, Chun,Liu, Yang,Shaw, Pang-Chui,Wang, Jian,Wen, Rui,Zhang, Lei
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- MULTIBIOTIC AGENTS AND METHODS OF USING THE SAME
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Multibiotic agents are disclosed. The multibiotic agents may contain two or more moieties linked through bonds cleavable in vivo. The bonds cleavable in vivo can be ester bonds, amide bonds, azo bonds, glycosidic bonds, carbonate linkers, or carbamate linkers. The moieties can be alcohol cores, amine cores, and/or acyls. Also disclosed are compositions containing multibiotic agents and methods of using the multibiotic agents.
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Page/Page column 152
(2019/01/06)
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- Selective methylation of kaempferol via benzylation and deacetylation of kaempferol acetates
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A strategy for selective mono-, di- and tri-O-methylation of kaempferol, predominantly on the basis of selective benzylation and controllable deacetylation of kaempferol acetates, was developed. From the selective deacetylation and benzylation of kaempferol tetraacetate (1), 3,4′,5,-tri-O-acetylkaempferol (2) and 7-O-benzyl-3,4′5,-tri-O-acetylkaempferol (8) were obtained, respectively. By controllable deacetylation and followed selective or direct methylation of these two intermediates, eight O-methylated kaempferols were prepared with 51-77% total yields from kaempferol.
- Mei, Qinggang,Wang, Chun,Yuan, Weicheng,Zhang, Guolin
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supporting information
p. 288 - 293
(2015/03/31)
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- Synthesis of icariin from kaempferol through regioselective methylation and para-Claisen - Cope rearrangement
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The hemisynthesis of the naturally occurring bioactive flavonoid glycoside icariin (1) has been accomplished in eleven steps with 7% overall yield from kaempferol. The 4?-OH methylation of kaempferol, the 8-prenylation of 3-O-methoxymethyl-4?-O-methyl-5- O-prenyl-7-O-benzylkaempferol (8) via para-Claisen-Cope rearrangement catalyzed by Eu(fod)3 in the presence of NaHCO3 , and the glycosylation of icaritin (3) are the key steps.
- Mei, Qinggang,Wang, Chun,Zhao, Zhigang,Yuan, Weicheng,Zhang, Guolin
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p. 1220 - 1225
(2015/08/18)
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- Cyanogenic and non-cyanogenic glycosides from Manihot esculenta (euphorbiaceae)
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A novel cyanogenic glycoside, 2-((6-0-(β-D-apiofuranosyl)-β- D-glucopyranosyloxy)-2-methylbutanenitrile, I, three novel non- cyanogenic glycosides, (2S)-((6-0-(β-D-apiofuranosyI)-β-D-gluco- pyranosyloxy) butane, 2; 2-((6-0-(β-D-apiofuranosyl)-β-D-gluco- pyranosyloxy) propane, 3, ethyl p-D-glucopyranosidc, 4, two known cyanogenic glycosides, (R)-2-(β-D-Glucopyranosyloxy)-2- methyl butanenitrile (lotaustralin), 5, 2-(β-D-Glucopyranosyloxy)- 2-methylpropane nitrile (linamarin), 6 have been isolated from ethanolic extract of the fresh rootcortex of Manihot esculenta. Lotaustralin and linamarin and two flavonoid glycosides, kaempferol-3-O- rutinosidc, 7 and quercctin-3-O-rutinoside, 8 have been isolated from the methanol extract of the fresh leaves of the same plant.
- Anam, Edet M.
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experimental part
p. 423 - 429
(2009/12/24)
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- Antileishmaniasis activity of flavonoids from Consolida oliveriana
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A set of flavonoids from Consolida oliveriana, kaempferol (1), quercetin (2), trifolin (3), and acetyl hyperoside (5) and their O-acetyl derivatives (1a, 2a, 3a), and octa-O-acetylhyperoside (4) showed leishmanicidal activity against promastigote as well as amastigote forms of Leishmania spp. The cellular proliferation, metabolic, and ultrastructural studies showed that the acetylated compounds 2a, 3a, and 4 were highly active against Leishmania (V.) peruviana, while 2a as well as 4 were effective against Leishmania (V.) braziliensis. These compounds were not cytotoxic and are effective at similar concentrations up to or lower than the reference drugs (pentostam and glucantim).
- Marin, Clotilde,Boutaleb-Charki, Samira,Diaz, Jesus G.,Huertas, Oscar,Rosales, Maria J.,Perez-Cordon, Gregorio,Guitierrez-Sanchez, Ramon,Sanchez-Moreno, Manuel
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experimental part
p. 1069 - 1074
(2011/04/19)
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- Cytotoxic activities of flavonoid glycoside acetates from Consolida oliveriana
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The flavonoids kaempferol, quercetin, trifolin, hyperoside 2″- and 6″- acetates, 7-glucotrifolin, biorobin and robinin were isolated from the aerial parts of Consolida oliveriana. Their derivatives kaempferol tetraacetate, quercetin pentaacetate, trifolin heptaacetate and hyperoside octaacetate exhibited significant cytotoxicity in vitro against three human cell lines HL-60, U937 and SK-MEL-1 while hyperoside 2″-acetate, hyperoside-6″-acetate, glucotrifolin decaacetate and heptamethyltrifolin were inactive. Georg Thieme Verlag KG Stuttgart.
- Diaz, Jesus G.,Carmona, Armando J.,Torres, Fernando,Quintana, Jose,Estevez, Francisco,Herz, Werner
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p. 171 - 174
(2008/09/20)
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- CYANOGENIC AND NON-CYANOGENIC GLYCOSIDES FROM MANIHOT ESCULENTA
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In addition to lotaustralin and linamarin, a novel cyanogenic glycoside, 2-((6-O-(β-D-apiofuranosyl)-β-D-glucopyranosyl)oxy)-2-methylbutanenitrile, two novel non-cyanogenic glycosides, (2S)-((6-O-(β-D-apiofuranosyl)-β-D-glucopyranosyl)oxy)butane and 2-((6-O-(β-D-apiofuranosyl)-β-D-glucopyranosyl)oxy)propane, and a simple non-cyanogenic glycoside, ethyl β-D-glucopyranoside, were isolated from an ethanolic extract of the fresh root cortex of manihot esculenta.From a methanolic extract of the fresh leaves of this species lotaustralin and linamarin, and two flavonoid glycosides, kaempferol-3-O-rutinoside and quercetin-3-O-rutinoside were isolated. - Keywords: Manihot esculenta; Euphorbiaceae; cassava; roots; leaves; cyanogenic glycosides; non-cyanogenic glycosides; flavonoids.
- Prawat, Hunsa,Mahidol, Chulabhorn,Ruchirawat, Somsak,Prawat, Uma,Tuntiwachwuttikul, Pittaya,et al.
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p. 1167 - 1174
(2007/10/02)
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- New Phenolic Components from Dalbergia Volubilis
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Phytochemical examination of non green branches of Dalbergia volubilis on extensive column and preparative thin layer chromatography yielded twelve compounds eight of which are already known compounds and were identified as sitosterol, 7-hydroxy-4-methyl-coumarin, dalbergin, biochanin-A, umbelliferone, p-hydroxy cinnamic acid, kaempferol and quercetin-3-O-glucoside.The other four compounds were new natural products, three of which were identified as novel 4-phenyl-2H-1-benzopyran-2-ones while the fourth one was a new 12a-hydroxy rotenoid.The structure of these new compounds has been established on the basis of chemical and spectral evidences and through derivatization, as 4',7-dihydroxy-3'-methoxy-4-phenyl-2H-1-benzopyran-2-one, 3',7-dihydroxy-4',5-dimethoxy-2H-1-benzopyran-2-one, 3',7-dihydroxy4',5-dimethoxy-6-formyl-2H-1-benzopyran-2-one and a complex rotenoid determined to be as (VII).The co-occurence of 4-methyl-2H-1-benzopyran-2-ones, 4-phenyl-2H-1-benzopyran-2-ones, isoflavones and rotenoids is of interest from biogenetic considerations.
- Chawla, H. Mohindra,Johny, C. J.,Mittal, Ram S.
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