Preparation of Amino Alcohols Condensed with Carbohydrates: Evaluation of Cytotoxicity and Inhibitory Effect on NO Production

Corrêa, Taís Arthur; Reis, Elaine F. C.; Alves, Lívia L.; Alves, Caio César de Souza; Castro, Sandra Bertelli Ribeiro de; Dias, Alyria Teixeira; Taveira, Aline F.; Hyaric, Mireille Le; Couri, Mara R.C.; Ferreira, Ana Paula; Almeida, Mauro Vieira de

doi:10.1111/j.1747-0285.2010.01026.x

Cited by 14 publications

(7 citation statements)

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“…Lipophilic drugs pass more easily through biological membranes than hydrophilic drugs, increasing their intracellular concentration and modulating signaling pathways, transcription factor activity, and gene expression (10,15). The genistein derivatives synthesized in this work showed different effects on NO, IL-12, and TNF-a production.…”

Section: Biological Evaluationmentioning

confidence: 86%

“…The nitrites production was quantified by comparing with a standard curve, made with different concentrations of NaNO 2 . The reading was measured in the microplate reader (Spectramax 190; Molecular Devices) at 540 nm wavelength (14,15).…”

Section: Griess Methodsmentioning

confidence: 99%

“…After 48 h of culture, the supernatant was removed and the cells were incubated with 100 lL of supplemented RPMI medium and 10 lL of MTT (5 mg ⁄ mL) for 4 h at 37°C in 5% CO. After this time, the reaction was stopped by adding to each well 100 lL of an acidic isopropanol solution (100 mL of isopropyl alcohol ⁄ 0.4 mL of HCl 10 N). Following 10 min of incubation at room temperature, the optical density (OD) values at 570 nm were determined (Spectramax 190; Molecular Devices, Sunnyvale, CA, USA) (14,15).…”

Section: Mtt Assaymentioning

confidence: 99%

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Synthesis of Lipophilic Genistein Derivatives and Their Regulation of IL‐12 and TNF‐α in Activated J774A.1 Cells

et al. 2012

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Genistein modulates inflammatory responses in part by reducing the production of the pro-inflammatory cytokines IL-12, TNF-a, and nitric oxide, by activated macrophages in response to lipopolysaccharide stimulus. Previous studies have shown that synthetic lipophilic genistein glycosides were significantly more active than hydrophilic glycosides. The aims of this study were to synthesize and to evaluate the effect of novel lipophilic genistein derivatives on IL-12, TNF-a, and nitric oxide production by J774A.1 cells. The results show that the modification of genistein enables the generation of non-cytotoxic compounds with increased IL-12 inhibition. However, these derivatives failed to inhibit TNF-a. The nitric oxide production was notably inhibited by the monoester (2, 3) and monoether (6, 7) compounds in a dose-dependent manner.

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Section: Biological Evaluationmentioning

confidence: 86%

Section: Griess Methodsmentioning

confidence: 99%

Section: Mtt Assaymentioning

confidence: 99%

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Synthesis of Lipophilic Genistein Derivatives and Their Regulation of IL‐12 and TNF‐α in Activated J774A.1 Cells

et al. 2012

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“…A correlation between hydrophobic character, membrane permeability and biological activity is frequently observed [18,19]. In this work, a novel analog of genistein, the 7-O-tetradecanoyl-genistein (TDG), was developed using esterification in vitro to bypass the in vivo processing, which favors biological activity and increased lipid solubility.…”

Section: Introductionmentioning

confidence: 99%

Immunomodulatory effects and improved prognosis of experimental autoimmune encephalomyelitis after O-tetradecanoyl-genistein treatment

Castro

O.R.

Alves

et al. 2012

International Immunopharmacology

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Experimental autoimmune encephalomyelitis (EAE) is a murine autoimmune disease used to study multiple sclerosis (MS), a human inflammatory demyelinating disease of the central nervous system. Genistein, an isoflavonoid phytoestrogenic compound found in soy, is known to reverse clinical signs of EAE. Although genistein has some potential in clinical application, it has some disadvantages related to its chemical structure, such as rapid in vivo metabolism and a fast decline in serum after oral administration. The present work investigates the treatment of EAE by using 7-O-tetradecanoyl-genistein (TDG), a more lipophilic analog of genistein obtained by esterification. The clinical course of EAE was investigated in C57Bl/6 mice immunized with myelin oligodendrocyte glycoprotein peptide (MOG)(35-55) in complete Freund's adjuvant supplemented with Mycobacterium tuberculosis H37RA. After 14 days of MOG immunization, mice were treated with TDG for seven days. Numbers of IL-17-producing cells and Foxp3 by CD4(+) T cells and CTLA-4 expression by CD3(+) T cells from brain were determined by flow cytometry. Levels of IL-6, IFN-γ and IL-10 were evaluated by ELISA. Brain sections were stained by hematoxylin and eosin method. The data obtained indicate that TDG treatment ameliorates the clinical signs of EAE, which correlates with a decrease of IL-17-producing cells and an increase in Foxp3(+)CD4(+) cells in the brain. TDG is also shown to enhance IL-10 production and CTLA-4 expression and to reduce IFN-γ and IL-6. Altogether, these findings suggest an immunomodulatory therapeutic role for TDG in EAE and multiple sclerosis.

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“…The present work describes the synthesis of novel anthraquinone derivatives conjugated with lipidic amino alcohols. This class of compounds has been shown to possess immune modulation activity and antiparasitic and antimicrobial properties (11)(12)(13)(14)(15)(16). The new compounds were evaluated for their effects on NO, IL-1b and TNF-a production in LPS/IFN-c-stimulated RAW264.7 macrophages.…”

mentioning

confidence: 99%

Synthesis of 1,4‐Anthracene‐9,10‐dione Derivatives and Their Regulation of Nitric Oxide, IL‐1β and TNF‐α in Activated RAW264.7 Cells

et al. 2013

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Mitoxantrone is an anthracenedione antineoplastic and immunosuppressive agent approved for multiple sclerosis treatment. Novel mono- and disubstituted anthraquinone derivatives, analogues of mitoxantrone, were synthesized through the addition of lipophilic amino alcohols and evaluated for their effect on IL-1β, TNF-α and nitric oxide production by LPS/IFN-γ-stimulated RAW264.7 cells. The disubstituted 1,4-anthracene-9,10-dione 10 showed significant inhibition of nitric oxide, TNF-α and IL-1β production at the concentration of 5 μg/mL, with a much lower cytotoxicity than mitoxantrone. The monosubstituted 3, 4, 11, 12 and 13 also displayed a moderate to good inhibitory capacity on IL-1β production. However, the methylated compounds 11, 12 and 13 failed to inhibit the TNF-α production, and compound 13 was the only one to decrease the production of nitric oxide. None of these derivatives was toxic at the tested concentrations. Compounds 10 and 13 had better inhibitory capacity of the inflammatory mediators analyzed, with reliable viability of the cells.

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Preparation of Amino Alcohols Condensed with Carbohydrates: Evaluation of Cytotoxicity and Inhibitory Effect on NO Production

Cited by 14 publications

References 14 publications

Synthesis of Lipophilic Genistein Derivatives and Their Regulation of IL‐12 and TNF‐α in Activated J774A.1 Cells

Synthesis of Lipophilic Genistein Derivatives and Their Regulation of IL‐12 and TNF‐α in Activated J774A.1 Cells

Immunomodulatory effects and improved prognosis of experimental autoimmune encephalomyelitis after O-tetradecanoyl-genistein treatment

Synthesis of 1,4‐Anthracene‐9,10‐dione Derivatives and Their Regulation of Nitric Oxide, IL‐1β and TNF‐α in Activated RAW264.7 Cells

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