- Metabolic Activation and Cytotoxicity of Aloe-Emodin Mediated by Sulfotransferases
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Aloe-emodin (AE) is a major anthraquinone ingredient of numerous traditional Chinese medicines with a variety of beneficial biological activities in vitro. Previous studies suggested that AE possessed cytotoxicity and genotoxicity. Nevertheless, the mechanisms of the toxic action of AE have not yet been fully clarified. The present study aimed at characterization of metabolic pathways of AE to better understand the mechanisms of AE-induced cytotoxicity. An AE-derived glutathione conjugate (AE-GSH) was observed in rat liver cytosol incubations containing AE and GSH, along with 3′-phosphoadenosine-5′-phosphosulfate (PAPS). Similar incubation fortified with N-acetylcysteine (NAC) in place of GSH offered an AE-NAC conjugate corresponding to the GSH conjugate. The formation of the two conjugates was found to require PAPS. The two conjugates were respectively detected in bile and urine of rats given AE. Sulfotransferase (SULT) inhibitor pentachlorophenol (PCP) suppressed the production of the observed AE-GSH/NAC conjugates in vivo, which suggested that SULTs participated in the process of the metabolic activation of AE. The presence of PCP attenuated cell susceptibility to AE-induced cytotoxicity. The present study illustrated potential association of sulfation-mediated bioactivation of AE with its cytotoxicity.
- Li, Ruihong,Li, Wei,You, Yutong,Guo, Xiucai,Peng, Ying,Zheng, Jiang
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- Anthraquinone natural product modified derivative
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The invention relates to the field of organic active small molecules, in particular to an anthraquinone natural product modified derivative, or a stereoisomer, a geometric isomer, a tautomer, a nitrogen oxide, a hydrate, a solvate, a metabolite, a pharmac
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Paragraph 0095; 0096
(2021/05/12)
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- Copper containing aloe emodin quaternary phosphonium salt, and synthesis method and applications thereof
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The invention discloses a copper containing aloe emodin quaternary phosphonium salt with anti-leukemia activity and a preparation method and applications thereof. The preparation method comprises following steps: reacting aloe emodin with excessive phosphorous tribromide to obtain aloe emodin bromide; then reacting aloe emodin bromide with tri-n-octyl phosphine to generate aloe emodin quaternary phosphonium salt; and finally reacting aloe emodin quaternary phosphonium salt with copper chloride dihydrate to obtain the copper containing aloe emodin quaternary phosphonium salt. The results of anin-vitro cancer cell inhibition experiment show that the provided compound can effectively inhibit the proliferation of leukemia cells, and can be used to develop anti-leukemia drugs.
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Paragraph 0010
(2020/05/01)
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- Aloe-emodin biquaternary ammonium salt with water solubility and anticancer activity and preparation thereof
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The present invention belongs to the field of preparation of the quaternary ammonium salt anticancer drugs, and in particular to aloe-emodin biquaternary ammonium salt with water solubility and anticancer activity and a preparation method thereof. Aloe-em
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Paragraph 0014
(2017/02/24)
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- Aloe-emodin quaternary ammonium salt alkyl iodoacetates with multiple-related anti-cancer mechanism
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The invention discloses aloe-emodin quaternary ammonium salt alkyl iodoacetates with the multiple-related anti-cancer mechanism and a preparation method thereof. The preparation method comprises the steps that firstly, aloe-emodin reacts with phosphorus tribromide to obtain brominated aloe-emodin; secondly, brominated aloe-emodin reacts with N-methyldi-n-octylamine to generate aloe-emodin quaternary ammonium salt; lastly, the aloe-emodin quaternary ammonium salt reacts with chloroacetyl chloride to generate iodine acetylation in the presence of sodium iodide to obtain aloe-emodin quaternary ammonium salt alkyl iodoacetates shown as a structural formula (please see the structural formula in the description). In-vitro cancer cell inhibition tests of aloe-emodin quaternary ammonium salt alkyl iodoacetates show that aloe-emodin quaternary ammonium salt alkyl iodoacetates has the good inhibitory activity on hematopoietic cells, is expected to be developed into anti-leukemia drugs and has the great application prospect.
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Paragraph 0013; 0015
(2018/01/19)
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- Novel emodin derivatives or pharmaceutically acceptable salt thereof, preparation method thereof and pharmaceutical composition for prevention or treatment of cancer disease containing the same as an active ingredient
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The present invention refers to novel mould amidine derivatives or a pharmaceutically acceptable salt, manufacturing method thereof and skin mitigating effect because of having medicament for treatment of preventing or cancer disease is directed to compositions. The present invention according to mould novel mould derived from is aloe amidine derivatives amidine derivatives introducing amino acid ester is manufactured by firing been significantly improved solubility in water, which is excellent in bioavailability thereby, inhibiting the growth of cancer cell significantly active same as active ingredient so that metals cancer compositions comprising pharmaceutical compositions for preventing or treating disease can be useful.
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Paragraph 0107 - 0109
(2016/10/17)
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- Preparation of 1,8-Di-O-alkylaloe-emodins and 15-amino-, 15-thiocyano-, and 15-selenocyanochrysophanol derivatives from aloe-emodin and studying their cytotoxic effects
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1,8-Di-O-alkylaloe-emodin derivatives (namely, methyl-, propyl-, hexyl-, dodecyl-, and octadecyl) were synthesized from naturally occurring aloe-emodin. Further, derivatives having various substituents such as diethylamino, pyrrolidinyl, piperidinyl, methylpiperazinyl, imidazolyl, thiocyano and selenocyano groups at the 15 position of chrysophanol and 1,8-di-O- hexylchrysophanol from aloe-emodin were synthesized. The cytotoxic effects of these derivatives on less P-glycoprotein (P-gp)-expressing HCT 116 cells and stably P-gp-expressing Hep G2 cells were evaluated by performing 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Among these products, several of them exhibited markedly higher potent cytotoxic effects not only on HCT116 cells but also Hep G2 cancer cells as compared to aloe-emodin.
- Cui, Xing-Ri,Takahashi, Kazutoshi,Shimamura, Takeshi,Koyanagi, Jyunichi,Komada, Fusao,Saito, Setsuo
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experimental part
p. 497 - 503
(2009/04/11)
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- Atropo-enantioselective total synthesis of knipholone and related antiplasmodial phenylanthraquinones
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The "lactone concept" has been efficiently employed for the first atropo-enantioselective synthesis of knipholone and related natural phenylanthraquinones. Besides the regio- and stereoselective construction of the biaryl axis, another important step was the "synthetically late" introduction of the C-acetyl group, either by a Friedel-Crafts type acetylation or by an ortho-selective Fries rearrangement first tested on simplified model systems and subsequently applied to the highly atroposelective preparation of the natural products and of simplified analogs thereof for biotesting. The synthetic availability of these natural biaryls, their precursors, and their unnatural analogs permitted a broader investigation of the antiplasmodial activities of these interesting biaryls.
- Bringmann, Gerhard,Menche, Dirk,Kraus, Juergen,Muehlbacher, Joerg,Peters, Karl,Peters, Eva-Maria,Brun, Reto,Bezabih, Merhatibeb,Abegaz, Berhanu M.
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p. 5595 - 5610
(2007/10/03)
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- Substituent Effects upon Peak Potentials and Reductive Cleavage Rate Constants of Hydroxy- and Methoxy-Substituted 9,10-Anthraquinones in 50percent Aqueous CH3CN: Do They Correlate?
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A variety of hydroxy- and methoxy-substituted 2-(acetoxymethyl)-9,10-anthraquinones (2a-7a) were reduced electrochemically and with dithionite (S2O42-) in 50percent aqueous CH3CN buffers over a wide pH range.Good to excellent yields of their corresponding reductive cleavage products, the substituted 2-methyl-9,10-anthraquinones 2b-7b, were obtained from most of these anthrachinone acetates, but only at higher pH.Rate constants for the reaction of 2-(acetoxymethyl)-9,10-anthraquinone (1a) with excess dithionite ranged from 1.0 x 10E-4 s-1 at pH values less than 7 to 4.0 x 10E- 4 s-1 at a pH of 10, demonstrating that loss of acetate occurs in the rate-determining step and that cleavage occurs slower via the anthrahydroquinone of 1a than the conjugate base of the anthrahydroquinone.Substituent effects upon the reductive cleavage process were determined by measuring rate constants for those acetates that react cleanly with dithionite at pH 8.These effects, which are rationalized on the basis of resonance theory and intramolecular H bonding, correlate fairly well with the peak potentials (Ep) of the reductive cleavage products of these acetates.Thus, electron-donating substituents on an anthraquinone acetate not only make it more difficult to reduce resulting in a more negative Ep but also enhance the rate of acetate cleavage in the corresponding anthrahydroquinone.
- Blankespoor, Ronald L.,Kosters, Elise L.,Post, Alan J.,VanMeurs, Derek P.
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p. 1609 - 1614
(2007/10/02)
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- Intercalating agents with covalent bond forming capability. A novel type of potential anticancer agents. 2. Derivatives of chrysophanol and emodin
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Fifty-one new C-methyl-modified derivatives of the anthraquinones chrysophanol and emodin or their various methyl ethers were prepared for structure-activity relationship studies of anticancer activity against mouse leukemia L1210 and human leukemia HL-60 cells. Representative compounds were spectrophotometrically studied for their capacity to interact with natural and denatured DNA. In general, those anthraquinones bearing an amino function interact with DNA. 1,8-Dimethoxyanthraquinones are incapable of intercalating into DNA. 1- or 8-Monohydroxymonomethoxyanthraquinones, however, interact with DNA to some extent. No straightforward correlation is apparent between the DNA-affinity data of the compounds studied spectrophotometrically and their cytotoxic effects. Cytotoxic potencies of these compounds on cell growth inhibition during a 72-h period are inversely correlated to their potencies when inhibiting [3H]TdR incorporation into DNA during the initial 30 min of exposure. Surprisingly, some compounds that showed more cytotoxicity did not inhibit initial TdR incorporation (0-30 min), while some others that strongly inhibited TdR incorporation initially did not exhibit cytotoxicity in 72 h. The results suggest that the cytotoxicity produced by these compounds is time dependent and is not a direct result of initial inhibition of DNA replication.
- Koyama,Takahashi,Chou,Darzynkiewicz,Kapuscinski,Kelly,Watanabe
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p. 1594 - 1599
(2007/10/02)
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- Anthracycline synthesis
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A process for synthesizing doxorubicin and related compounds from aloe-emodin is disclosed. Intermediates useful in the preparation of doxorubicin and related compounds are also disclosed.
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