- (-)-Epigallocatechin gallate derivatives reduce the expression of both urokinase plasminogen activator and plasminogen activator inhibitor-1 to inhibit migration, adhesion, and invasion of MDA-MB-231 cells
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Urokinase plasminogen activator (uPA) and its inhibitor plasminogen activator inhibitor-1 (PAI-1) are established independent biomarkers for high metastasis risk in breast cancer. In this study, we investigated the regulatory activity of (-)-epigallocatechin-3-gallate (EGCG) and its derivatives on uPA and PAI-1 expression and thereby their anti-metastatic potential. EGCG showed only marginal effects on the uPA system and on the metastatic behavior of breast cancer cells (MDA-MB-231). However, the EGCG derivative 3e with a methyl-substituted carbonate substituent at the 4″-position showed potent inhibition of PAI-1 (62%) and uPA (50%) expression. The Ras-extracellular-signal-regulated kinase (ERK), p38 mitogen-activated protein kinase (MAPK), and phosphatidylinositol-3-kinase (PI3K)/Akt/NF-κB pathways, which regulate uPA and PAI-1 expression, were also affected by 3e (25%, 45%, and 25% reduction, respectively). In line with these findings, substantial reduction in metastatic behavior of MDA-MB-231 cells, such as adhesion (40%), invasion (56%), and migration (40%), was observed in the presence of 3e. It is also noteworthy that, in MDA-MB-231 cells, 3e did not exert any beneficial effect on the expression of matric metalloprotein (MMP) 2 and 9, which indicates that the anti-metastatic activity of 3e in MDA-MB-231 cells is not related to its regulation of the expression of MMPs. Taken together, we have shown that the EGCG derivative 3e could suppress the metastatic behavior of MDA-MB-231 cells through regulation of uPA and PAI-1.
- Shin, Sunhye,Kim, Mi Kyoung,Jung, Woong,Chong, Youhoon
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- Structural Modification of (-)-Epigallocatechin Gallate (EGCG) Shows Significant Enhancement in Mitochondrial Biogenesis
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(-)-Epigallocatechin-3-gallate (EGCG) is known as a mitochondria-targeted molecule that can prevent mitochondrial deterioration and induce mitochondrial biogenesis by modulating key regulators of mitochondrial metabolism. In this study, we tackled whether derivatization of EGCG could result in enhancement of its effects on mitochondrial biogenesis. EGCG, EGCG peracetate (AcEGCG), and its 4″-O-alkyl substituted congeners prepared by previously reported procedures were biologically evaluated. Interestingly, EGCG and AcEGCG were only marginally effective in inducing mitochondrial biogenesis, while AcEGCG congeners with an alkyl group at the 4″-O position showed significantly increased biological activity compared to their parent compound. Among these series, 3f with a methyl-branched carbonate chain at the 4″-O position of the AcEGCG scaffold showed the most enhancement in inducing mitochondrial biogenesis. Hepa1-6 cells treated with 3f exhibited increases in both mitochondrial mass (1.5 times) and relative mtDNA content to nDNA (1.5 times). As a mitochondrial biogenesis enhancer, 3f also increased expression levels of regulators for mitochondrial function, including PGC-1α (4.0 fold), p-AMPK (2.5 fold), SIRT1 (4.2 fold), ERRα (1.8 fold), NRF-1 (1.6 fold), NRF-2 (1.7 fold), and mtTFA (1.6 folds). Investigation of oxidative phosphorylation by mitochondria in the presence of 3f revealed that 3f increased the NAD+/NADH ratio, the amount of cytochrome c, ATP synthesis, and oxygen consumption in Hepa1-6 cells by 2.2, 1.4, 1.5, and 2.1 fold, respectively. Taken together, these results warrant an extensive structure-activity relationship study for EGCG derivatives to develop novel mitochondrial biogenesis enhancers.
- Ha, Taewoong,Kim, Mi Kyoung,Park, Kwang-Su,Jung, Woong,Choo, Hyunah,Chong, Youhoon
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- FLAVAN-3-OLS AND PROANTHOCYANIDINS FROM CISTUS INCANUS
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Four monomeric and seven oligomeric flavanoids have been identified from a Cistus incanus subspecies traditionally used for treatment of skin diseases in northern parts of Greece and identified as subsp. tauricus.Flavan-3-ols are (+)-catechin, (+)-gallocatechin, the novel (+)-gallocatechin 3-gallate and the rarely occurring (+)-catechin 3-O-α-L-rhamnoside; proanthocyanidins are procyanidins B1 and B3, gallocatechin-(4α->8)-gallocatechin, its novel (4α->6)-regioisomer, gallocatechin-(4α->8)-catechin, the tentatively identified novel catechin-(4α->8)-gallocatechin and the trimer gallocatechin-(4α->8)-gallocatechin-(4α->8)-catechin.The uncommon flavanone 2R,3R-dihydromyricetin was also obtained.
- Petereit, Frank,Kolodziej, Herbert,Nahrstedt, Adolf
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- Solubility Determination and Modeling of EGCG Peracetate in 12 Pure Solvents at Temperatures from 278.15 to 318.15 K
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The solubility of (-)-epigallocatechin gallate (EGCG) peracetate in 12 pure solvents (methanol, ethanol, 1-propanol, 1-butanol, 2-propanol, 2-butanol, 1-pentanol, 1-hexanol, 2-methoxyethanol, 2-ethoxyethanol, 2-propoxyethanol, and 2-butoxyethanol) was measured using the static method at the temperature range 278.15-318.15 K under atmospheric pressure. The solubility of EGCG peracetate in the selected solvents increased with increasing temperature in 12 solvents, and the most notable change was found in methanol. The obtained solubility data were correlated with the van't Hoff equation, the modified Apelblat equation, the λh equation, and the nonrandom two-liquid model. Furthermore, solid forms of EGCG peracetate in 12 pure solvents were studied by a scanning electron microscope and X-ray powder diffraction. The obtained solubility values would be helpful in the purification and crystallization process of EGCG peracetate.
- Liu, Bingbing,Asadzadeh, Behnaz,Yan, Weidong
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- (-)-epigallocatechin gallate prodrugs , preparation method thereof and composition for mitochondrial biosis
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The present invention relates to an epigallocatechin gallate prodrug, a method for manufacturing the same, and a composition for promoting mitochondrial biosynthesis comprising the same. A compound represented by chemical formula (1) according to the present invention increases the activity of PGC-1andalpha;, AMPK, and SIRT1, known as mitochondrial biosynthesis regulators, increases the amount of mitochondrial DNA, and increases a NAD+/NADH ratio, a level of cytochrome c, the synthesis of ATP, and oxygen consumption, thereby confirming an effect of increasing the mitochondrial activity and biosynthesis. In addition, it is confirmed that the compound has an effect of having a high absorption rate and slow metabolism in vivo compared to an existing epigallocatechin gallate, thereby being useful for a purpose of preventing or treating diseases related to mitochondrial dysfunction.COPYRIGHT KIPO 2020
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Paragraph 0169; 0172; 0173
(2019/12/31)
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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 41-42
(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; 69
(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 54; 149
(2019/12/28)
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- Epigallocatechin gallate derivatives preparation method
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The invention mainly aims at achieving lipid-solubility transformation of epigallocatechin gallate which is polyhydroxy, good in water solubility and low in bioavailability, including three ways, namely encapsulating hydroxyl with different anhydrides so
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Paragraph 0015; 0017; 0018; 0019
(2018/11/22)
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- Glucopyranose group-substituted EGCG (Epigallocatechin Gallate) compound as well as preparation method and application thereof
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The invention belongs to the field of drug treatment and particularly relates to a glucopyranose group-substituted compound EGCG (Epigallocatechin Gallate) as well as a preparation method and application thereof. The formula I of the glucopyranose group-substituted EGCG compound is described in the specification. Optical active bodies or racemates of the compound and salts thereof and monomers ormixture of diastereoisomers are used for preparing medicines resisting the Alzheimer disease.
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Paragraph 0038; 0039
(2018/04/28)
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- Regioselective synthesis of alkyl EGCG derivatives
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The present invention relates to a synthesis method for regioselective alkylation of ((-)-epigallocatechin gallate (-)-EGCG), and in the regioselective alkylation of the (-)-EGCG according to the present invention, EGCG is firstly acetylated and alkylated
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Paragraph 0067-0069
(2018/04/12)
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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 88
(2019/01/06)
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- Facile synthesis of 4″-O-alkyl-(–)-EGCG derivatives through regioselective deacetylative alkylation
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Therapeutic potential of the D-ring methyl ethers of (–)-epigallocatechin-3-gallate [(–)-EGCG] warrants extensive structure–activity relationship study of various D-ring ethers of (–)-EGCG but, for this purpose, efficient synthetic strategy needs to be de
- Seo, Yujin,Kim, Mi Kyoung,Choo, Hyunah,Chong, Youhoon
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p. 655 - 659
(2017/03/27)
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- The design, synthesis and biological evaluation of pro-EGCG derivatives as novel anti-vitiligo agents
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With the aim of overcoming the instability and poor membrane permeability of epigallocatechin-3-gallate (EGCG), a series of prodrugs of EGCG and its derivatives (pro-EGCGs) were designed and synthesized, and their protective effect on melanocytes against
- Wang, Siyu,Jin, Rong,Wang, Ruiquan,Hu, Yongzhou,Dong, Xiaowu,Xu, Ai e
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p. 106308 - 106315
(2016/11/23)
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- Synthesis and structure-activity relationship of 3-O-acylated (-)-epigallocatechins as 5α-reductase inhibitors
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A series of 3-O-acylated (-)-epigallocatechins were synthesized and their inhibition of steroid 5α-reductase was studied. They were prepared from the reaction of EGCG with tert-butyldimethylsilyl chloride followed by reductive cleavage of the ester bond. The resultant (-)-epigallocatechins penta-O-tert-butyldimethylsilyl ether was esterified with different fatty acids then desilylated to provide the corresponding products. The activity of 3-O-acylated (-)-epigallocatechins increased with the increasing carbon numbers of the fatty acid moiety, reaching maximum for 16 carbon atoms (compound 4h) with an IC50 of 0.53 μM, which was ~12-fold more potent than EGCG (IC50 = 6.29 μM). Introduction of monounsaturated fatty acid provided the most potent compound 6 (IC50 = 0.48 μM), which showed moderate anti-tumor activity in vivo.
- Lin, Shu Fu,Lin, Yu-Hsiang,Lin, Mengju,Kao, Yi-Feng,Wang, Ru-Wen,Teng, Li-Wei,Chuang, Shih-Hsien,Chang, Jia-Ming,Yuan, Ta-Tung,Fu, Kuo Chu,Huang, Kuan Pin,Lee, Ying-Shuen,Chiang, Chao-Cheng,Yang, Sheng-Chuan,Lai, Chun-Liang,Liao, Chu-Bin,Chen, Paonien,Lin, Young-Sun,Lai, Kuei-Tai,Huang, Hung-Jyun,Yang, Ju-Ying,Liu, Chia-Wei,Wei, Win-Yin,Chen, Chi-Kuan,Hiipakka, Richard A.,Liao, Shutsung,Huang, Jiann-Jyh
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experimental part
p. 6068 - 6076
(2011/01/13)
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- Enhanced anti-influenza A virus activity of (-)-epigallocatechin-3-O-gallate fatty acid monoester derivatives: Effect of alkyl chain length
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A series of fatty acid monoester derivatives of (-)-epigallocatechin-3-O-gallate (EGCG) were prepared by one-pot lipase-catalyzed transesterification. The introduction of long alkyl chains enhanced anti-influenza A/PR8/34 (H1N1) virus activity 24-fold relative to native EGCG.
- Mori, Shuichi,Miyake, Shinya,Kobe, Takayoshi,Nakaya, Takaaki,Fuller, Stephen D.,Kato, Nobuo,Kaihatsu, Kunihiro
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experimental part
p. 4249 - 4252
(2009/04/07)
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- (-)-EPIGALLOCATECHIN GALLATE DERIVATIVES FOR INHIBITING PROTEASOME
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(-)-EGCG, the most abundant catechin, was found to be chemopreventive and anticancer agent. However, (-)-EGCG has at least one limitation: it gives poor bioavailability. This invention provides compounds of generally formula 10, wherein R1 is selected from the group of--H and C1 to C6 acyl group; R2, R3, and R4 are each independently selected from the group of--H,--OH, and C1 to C6 acyloxyl group; and at least one of R2, R3, or R4 is--H. The derivatives of (-)-EGCG that is at least as potent as (-)-EGCG. The carboxylate protected forms of (-)-EGCG and its derivatives are found to be more stable than the unprotected forms, which can be used as proteasome inhibitors to reduce tumor cell growth.
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(2008/06/13)
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- Synthesis of (-)-[4-3H]epigallocatechin gallate and its metabolic fate in rats after intravenous administration.
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Because a great deal of attention has been focused on the metabolism of (-)-epigallocatechin gallate (EGCg), quantitative analysis of this compound is required. For this purpose we developed a method of chemical synthesis of [4-(3)H]EGCg. Synthesized [4-(3)H]EGCg showed 99.5% radiochemical purity and a specific activity of 13 Ci/mmol. To clarify the excretion route of EGCg, the radioactivity levels of bile and urine were quantified after intravenous administration of [4-(3)H]EGCg to bile-duct-cannulated rats. Results showed that the radioactivity of the bile sample excreted within 48 h accounted for 77.0% of the dose, whereas only 2.0% of the dose was recovered in the urine. The excretion ratio of bile to urine was calculated to be about 97:3. These results clearly showed that bile was the major excretion route of EGCg. Time-course analysis of the radioactivity in blood was also performed to estimate the pharmacokinetic parameters following intravenous administration of [4-(3)H]EGCg. In addition, EGCg metabolites excreted in the bile within 4 h after the intravenous dose of [4-(3)H]EGCg were analyzed by HPLC. The results showed that 4',4"-di-O-methyl-EGCg was present in the conjugated form and made up about 14.7% of the administered radioactivity.
- Kohri,Nanjo,Suzuki,Seto,Matsumoto,Yamakawa,Hojo,Hara,Desai,Amin,Conaway,Chung
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p. 1042 - 1048
(2007/10/03)
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