- New lipophenols prevent carbonyl and oxidative stresses involved in macular degeneration
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Dry age-related macular degeneration and Stargardt disease undergo a known toxic mechanism caused by carbonyl and oxidative stresses (COS). This is responsible for accumulation in the retinal pigment epithelium (RPE) of A2E, a main toxic pyridinium bis-retinoid lipofuscin component. Previous studies have shown that carbonyl stress in retinal cells could be reduced by an alkyl-phloroglucinol-DHA conjugate (lipophenol). Here, we performed a rational design of different families of lipophenols to conserve anti-carbonyl stress activities and improve antioxidant properties. Five synthetic pathways leading to alkyl-(poly)phenol derivatives, with phloroglucinol, resveratrol, catechin and quercetin as the main backbone, linked to poly-unsaturated fatty acid, are presented. These lipophenols were evaluated in ARPE-19 cell line for their anti-COS properties and a structure-activity relationship study is proposed. Protection of ARPE-19 cells against A2E toxicity was assessed for the four best candidates. Finally, interesting anti-COS properties of the most promising quercetin lipophenol were confirmed in primary RPE cells.
- Moine, Espérance,Boukhallat, Manel,Cia, David,Jacquemot, Nathalie,Guillou, Laurent,Durand, Thierry,Vercauteren, Joseph,Brabet, Philippe,Crauste, Céline
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- Water-soluble and cleavable quercetin-amino acid conjugates as safe modulators for P-glycoprotein-based multidrug resistance
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Quercetin-amino acid conjugates with alanine or glutamic acid moiety attached at 7-O and/or 3-O position of quercetin were prepared, and their multidrug resistance (MDR)-modulatory effects were evaluated. A quercetin-glutamic acid conjugate, 7-O-Glu-Q (3a
- Kim, Mi Kyoung,Choo, Hyunah,Chong, Youhoon
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- LIPOPHENOLIC FLAVONOID DERIVATIVES USEFUL TO REDUCE CARBONYL AND OXIDATIVE STRESSES (COS)
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The invention relates to compound of formula (I): in particular flavonoid derivatives (quercetin and catechin derivatives), for use in the prevention and/or the treatment of a disease or disorder involving both carbonyl and oxidative stresses.
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- Quercetin derivative and its preparation method and application
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The invention discloses a quercetin derivative and a preparation method and application thereof. The preparation method comprises the following steps: firstly using dichlorodiphenylmethane to protect quercetin o-diphenol hydroxyl, combining a benzyl protection group to obtain the selectively protected quercetin derivative, and then independently reacting with dimethyl sulfate, diethyl sulfate, allyl bromide, paratoluensulfonyl chloride and acetic anhydride respectively to generate corresponding quercetin derivatives. All of the prepared derivative compounds have NRK-49F proliferation activity inhibition superior to that of quercetin. The quercetin derivatives 20a-1, 14a-1 and 23d-1 compositely replaced by methyl and p-tosyl have higher inhibition NRK-49F proliferation activity, and the inhibition ratio respectively reaches 86.33%, 78.04% and 75.91%. Thus, the currently obtained quercetin derivative compounds have obvious inhibition effect on kidney fibroblast NRK-49F proliferation.
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- Quercetin derivatives as novel antihypertensive agents: Synthesis and physiological characterization
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The antihypertensive flavonol quercetin (Q1) is endowed with a cardioprotective effect against myocardial ischemic damage. Q1 inhibits angiotensin converting enzyme activity, improves vascular relaxation, and decreases oxidative stress and gene expression. However, the clinical application of this flavonol is limited by its poor bioavailability and low stability in aqueous medium. In the aim to overcome these drawbacks and preserve the cardioprotective effects of quercetin, the present study reports on the preparation of five different Q1 analogs, in which all OH groups were replaced by hydrophobic functional moieties. Q1 derivatives have been synthesized by optimizing previously reported procedures and analyzed by spectroscopic analysis. The cardiovascular properties of the obtained compounds were also investigated in order to evaluate whether chemical modification affects their biological efficacy. The interaction with β-adrenergic receptors was evaluated by molecular docking and the cardiovascular efficacy was investigated on the ex vivo Langendorff perfused rat heart. Furthermore, the bioavailability and the antihypertensive properties of the most active derivative were evaluated by in vitro studies and in vivo administration (1 month) on spontaneously hypertensive rats (SHRs), respectively. Among all studied Q1 derivatives, only the ethyl derivative reduced left ventricular pressure (at 10- 8 M ÷ 10- 6 M doses) and improved relaxation and coronary dilation. NOSs inhibition by L-NAME abolished inotropism, lusitropism and coronary effects. Chronic administration of high doses of this compound on SHR reduced systolic and diastolic pressure. Differently, the acetyl derivative induced negative inotropism and lusitropism (at 10- 10 M and 10- 8 ÷ 10- 6 M doses), without affecting coronary pressure. Accordingly, docking studies suggested that these compounds bind both β1/β2-adrenergic receptors. Taking into consideration all the obtained results, the replacement of OH with ethyl groups seems to improve Q1 bioavailability and stability; therefore, the ethyl derivative could represent a good candidate for clinical use in hypertension.
- Grande, Fedora,Parisi, Ortensia I.,Mordocco, Roberta A.,Rocca, Carmine,Puoci, Francesco,Scrivano, Luca,Quintieri, Anna M.,Cantafio, Patrizia,Ferla, Salvatore,Brancale, Andrea,Saturnino, Carmela,Cerra, Maria C.,Sinicropi, Maria S.,Angelone, Tommaso
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p. 161 - 170
(2015/12/11)
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- Quercetin-POC conjugates: Differential stability and bioactivity profiles between breast cancer (MCF-7) and colorectal carcinoma (HCT116) cell lines
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In the course of our ongoing efforts to develop novel quercetin conjugates with enhanced stability profiles, we introduced an isopropyloxycarbonylmethoxy (POC) group to 7-OH and/or 3-OH of quercetin and prepared three novel quercetin conjugates. The querc
- Cho, Suh Young,Kim, Mi Kyoung,Park, Kwang-Su,Choo, Hyunah,Chong, Youhoon
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p. 1671 - 1679
(2013/05/08)
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- Enhanced stability and intracellular accumulation of quercetin by protection of the chemically or metabolically susceptible hydroxyl groups with a pivaloxymethyl (POM) promoiety
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In order to increase stability of quercetin, its metabolically and chemically susceptible hydroxyl groups 7-OH and 3-OH respectively were transiently blocked with a pivaloxymethyl (POM) promoiety to provide two novel quercetin conjugates [7-O-POM-Q (2), 3
- Kim, Mi Kyoung,Park, Kwang-Su,Lee, Chaewoon,Park, Hye Ri,Choo, Hyunah,Chong, Youhoon
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experimental part
p. 8597 - 8607
(2011/02/25)
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