Quantitative structure–activity relationship to predict differential inhibition of aldose reductase by flavonoid compounds

Fernández, Michael; Caballero, Julio; Helguera, Aliuska Morales; Castro, Eduardo A.; González, Maykel Pérez

doi:10.1016/j.bmc.2005.02.038

Cited by 86 publications

(53 citation statements)

References 32 publications

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“…Their chemical structures were elucidated by spectral analysis as; protocatechuic acid (1), ethyl gallate (2), fustin (3), morin hydrate (4), fisetin (5), sulfuretin (6), quercetin (7), butein (8), and pentagalloyl glucose (9). Their structures are shown in Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Several studies of naturally occurring flavonoids on the inhibition of ALR2 and AGEs, and their structure-activity relationship have been reported. [9][10][11] Increased oxidative stress is a widely accepted participant in the development and progression of diabetes and their complications. Diabetes is usually accompanied by an increased production of free radicals and/or impaired antioxidant defenses.…”

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confidence: 99%

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Inhibitory Effect of the Compounds Isolated from Rhus verniciflua on Aldose Reductase and Advanced Glycation Endproducts

Lee

Song

Lee

et al. 2008

Biological & Pharmaceutical Bulletin

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Increased polyol pathway due to aldose reductase activation and advanced glycation endproducts (AGEs) formation have been implicated as an important molecular mechanism of how hyperglycemia causes diabetic complications. 1)Aldose reductase (alditol/NADP ϩ oxidoreductase, EC 1.1.1.21, ALR2) is the first enzyme of the polyol pathway which reduces excess D-glucose into D-sorbitol with concomitant conversion of NADPH to NADP ϩ , 2,3) which has been demonstrated to play important roles not only in the cataract formation in the lens 4) but also in the pathogenesis of diabetic complications such as neuropathy, 5) nephropathy 6) and retinopathy. 7)Prolonged hyperglycemia can also result in the formation of AGEs in body tissues. The complex, fluorescent AGE molecules formed during the Maillard reaction can lead to protein cross-linking and contribute to the development and progression of several diabetic complications such as cataract, atherosclerosis, nephropathy and neuropathy. 8) Since the discovery that ALR2 and AGEs may play an important role in pathogenesis of diabetic complications, several synthetic and naturally occurring compounds have been studied for their in vitro and in vivo activities. Several studies of naturally occurring flavonoids on the inhibition of ALR2 and AGEs, and their structure-activity relationship have been reported. [9][10][11] Increased oxidative stress is a widely accepted participant in the development and progression of diabetes and their complications. Diabetes is usually accompanied by an increased production of free radicals and/or impaired antioxidant defenses. 12,13) It would therefore seem desirable that ALR2 inhibitors possess AGEs inhibitory and antioxidative potencies.Rhus verniciflua grows particularly in South East Asia and the biological activities of this plant have been reported as anti-inflammatory, 14) anti-cancer, 15) and anti-rheumatoid arthritis, 16) etc.In the present study, we investigated the inhibitory effect of the bark of R. verniciflua on ALR2 and AGEs to evaluate its potential use for the treatment of diabetic complications. This investigation led to the isolation and identification of the compounds that inhibit the activity of ALR2 and AGEs. Furthermore, we investigated whether the active compound for ALR2 and AGEs was able to scavenge free radical using luminometry (Photochem ® ). MATERIALS AND METHODSChemicals First grade solvents were used for extraction, fractionation and column chromatography. Kiesel gel 60 (70-230 mesh, Art, 7734 Merck) was used as the column packing material. Kiesel 60 F 254 (precoated plate, Art. 5559, Merck) was used for thin layer chromatography (TLC). Iodine vapor and 10% H 2 SO 4 were used for TLC detection. DLGlyceraldehyde, D-glucose, bovine serum albumin (BSA), DTT and NADPH were purchased from Sigma Chemical (St. Louis, MO, U.S.A.). Ampicillin, IPTG and imidazole were purchased from USB Corporation (Cleveland, OH, U.S.A.). Human ALR2 cDNA clone was purchased from 21C Frontier Human Gene Bank (Daejeon, Korea).Plant Materials The...

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Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

Inhibitory Effect of the Compounds Isolated from Rhus verniciflua on Aldose Reductase and Advanced Glycation Endproducts

Lee

Song

Lee

et al. 2008

Biological & Pharmaceutical Bulletin

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“…Several studies on the inhibition of ALR2 and AGEs and structure-activity relationship of naturally occurring flavonoids have been reported. [12][13][14] Black bamboo, Phyllostachys nigra grows particularly in Southeast Asia and represents a traditionally important commodity used for building materials in traditional medicine, and as a source of food, which are a potential source of natural free radical scavengers. 15) In the present study, we investigated the inhibitory effect of the leaves of P. nigra on ALR2 and AGEs to evaluate its potential for treatment of diabetic complications.…”

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confidence: 99%

Aldose Reductase and Advanced Glycation Endproducts Inhibitory Effect of Phyllostachys nigra

Jung

Lee

et al. 2007

Biological & Pharmaceutical Bulletin

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“…They possess a wide variety of biological activities including antiinflammatory, antimicrobial, antiallergenic, antiviral, vasodilatory action and antioxidant activity. These compounds are able either to suppress free radical formation and chain initiation or to scavenge free radical and chain propagation (Fernández et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

13C NMR spectral data and molecular descriptors to predict the antioxidant activity of flavonoids

Scotti

Fernandes

Muramatsu

et al. 2011

Braz. J. Pharm. Sci.

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Tissue damage due to oxidative stress is directly linked to development of many, if not all, human morbidity factors and chronic diseases. In this context, the search for dietary natural occurring molecules with antioxidant activity, such as flavonoids, has become essential. In this study, we investigated a set of 41 flavonoids (23 flavones and 18 flavonols) analyzing their structures and biological antioxidant activity. The experimental data were submitted to a QSAR (quantitative structure-activity relationships) study. NMR 13 C data were used to perform a Kohonen self-organizing map study, analyzing the weight that each carbon has in the activity. Additionally, we performed MLR (multilinear regression) using GA (genetic algorithms) and molecular descriptors to analyze the role that specific carbons and substitutions play in the activity.Uniterms: Flavonoids/antioxidant activity. 13C NMR. Kohonen self-organizing map.Danos aos tecidos devido ao estresse oxidativo estão diretamente ligados ao desenvolvimento de muitos, senão todos, os fatores de sedentarismo e de doenças crônicas. Neste contexto, a busca de moléculas naturais, que participam da nossa dieta e que possuam atividade antioxidante, flavonóides, torna-se de grande interesse. Neste estudo, nós investigamos um conjunto de 41 flavonóides (23 flavonas e 18 flavonóis), relacionando suas estruturas e atividade antioxidante. Os dados experimentais foram submetidos à análise de QSAR (relações quantitativas estrutura-atividade). Dados de RMN 13 C foram utilizados para realizar um estudo do mapa auto-organizável de Kohonen, analisando o peso que cada carbono tem na atividade. Além disso, realizamos uma MLR (regressão múltipla) usando GA (algoritmos genéticos) e descritores moleculares para avaliar a influência de carbonos e substituições na atividade. Unitermos: RMN 13C. Flavonóides/atividade antioxidante. Mapa auto-organizável de Kohonen.

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Quantitative structure–activity relationship to predict differential inhibition of aldose reductase by flavonoid compounds

Cited by 86 publications

References 32 publications

Inhibitory Effect of the Compounds Isolated from Rhus verniciflua on Aldose Reductase and Advanced Glycation Endproducts

Inhibitory Effect of the Compounds Isolated from Rhus verniciflua on Aldose Reductase and Advanced Glycation Endproducts

Aldose Reductase and Advanced Glycation Endproducts Inhibitory Effect of Phyllostachys nigra

13C NMR spectral data and molecular descriptors to predict the antioxidant activity of flavonoids

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