Structure–activity relations on [1-(3,5-difluoro-4-hydroxyphenyl)-1H-pyrrol-3-yl]phenylmethanone. The effect of methoxy substitution on aldose reductase inhibitory activity and selectivity

Chatzopoulou, Maria; Mamadou, Eduard; Juskova, Maria; Koukoulitsa, Cathrine; Nicolaou, Ioannis; Štefek, Milan; Demopoulos, Vassilis J.

doi:10.1016/j.bmc.2011.01.009

Cited by 26 publications

(9 citation statements)

References 39 publications

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“…As a result, there is an increased tendency of many substrates or ligands to bind with both ALR1 and ALR2. The inhibition of both the enzymes is thought to lead to toxic phenomena, due to the resulting insufficient detoxification capacity of the living cell (Chatzopoulou et al 2011). In the present study, ALR1 inhibitory activity was evaluated on partially purified ALR1 obtained from rat's kidney.…”

Section: Radical Scavenging Activity (Dpph ⋅ CL Lox Tests) Alr2/amentioning

confidence: 99%

Phytochemical analysis with the antioxidant and aldose reductase inhibitory capacities of Tephrosia humilis aerial parts’ extracts

Plioukas

Gabrieli

Lazari

et al. 2015

Natural Product Research

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The aerial parts of Tephrosia humilis were tested about their antioxidant potential, their ability to inhibit the aldose/aldehyde reductase enzymes and their phenolic content. The plant material was exhaustively extracted with petroleum ether, dichloromethane and methanol, consecutively. The concentrated methanol extract was re-extracted, successively, with diethyl ether, ethyl acetate and n-butanol. All extracts showed significant antioxidant capacity, but the most effective was the ethyl acetate extract. As about the aldose reductase inhibition, all fractions, except the aqueous, were strong inhibitors of the enzyme, with the n-butanolic and ethyl acetate fractions to inhibit the enzyme above 75%. These findings provide support to the ethnopharmacological usage of the plant as antioxidant and validate its potential to act against the long-term diabetic complications. The phytochemical analysis showed the presence of 1,4-dihydroxy-3,4-(epoxyethano)-5-cyclohexene(1), cleroindicin E(2), lupeol(3), methyl p-coumarate(4), methyl 4-hydroxybenzoate(5), prunin(6), 5,7,2',5'-tetrahydroxyflavanone 7-rutinoside(7), protocatechuic acid(8), luteolin 7-glucoside(9), apigenin(10), naringin(11), rhoifolin(12) and luteolin 7-glucuronate(13).

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Section: Radical Scavenging Activity (Dpph ⋅ CL Lox Tests) Alr2/amentioning

confidence: 99%

Phytochemical analysis with the antioxidant and aldose reductase inhibitory capacities of Tephrosia humilis aerial parts’ extracts

Plioukas

Gabrieli

Lazari

et al. 2015

Natural Product Research

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show abstract

“…A previously described protocol was used (Chatzopoulou et al, 2011), with the exception that Sigma-Aldrich M-199 (M 3769) was the incubation medium at pH 7.4. Briefly, freshly dissected lenses were incubated individually in 1.5 ml of M-199 medium for 3 hours at 37°C, into which 5% CO 2 , 95% O 2 was bubbled at regular intervals.…”

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confidence: 99%

Molecular Interactions and Implications of Aldose Reductase Inhibition by PGA₁ and Clinically Used Prostaglandins

Díez-Dacal¹,

Sánchez‐Gómez

Sánchez‐Murcia

et al. 2015

Mol Pharmacol

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Aldose reductase (AKR1B1) is a critical drug target because of its involvement in diabetic complications, inflammation, and tumorigenesis. However, to date, development of clinically useful inhibitors has been largely unsuccessful. Cyclopentenone prostaglandins (cyPGs) are reactive lipid mediators that bind covalently to proteins and exert anti-inflammatory and antiproliferative effects in numerous settings. By pursuing targets for modification by cyPGs we have found that the cyPG PGA 1 binds to and inactivates AKR1B1. A PGA 1 -AKR1B1 adduct was observed, both by matrix-assisted laser desorption/ ionization time-of-flight mass spectrometry and by SDS-PAGE using biotinylated PGA 1 (PGA 1 -B). Insight into the molecular interactions between AKR1B1 and PGA 1 was advanced by molecular modeling. This anticipated the addition of PGA 1 to active site Cys298 and the potential reversibility of the adduct, which was supported experimentally. Indeed, loss of biotin label from the AKR1B1-PGA 1 -B adduct was favored by glutathione, indicating a retro-Michael reaction, which unveils new implications of cyPG-protein interaction. PGA 1 elicited only marginal inhibition of aldehyde reductase (AKR1A1), considered responsible for the severe adverse effects of many AKR1B1 inhibitors. Interestingly, other prostaglandins (PGs) inhibited the enzyme, including non-electrophilic PGE 1 and PGE 2 , currently used in clinical practice. Moreover, both PGA 1 and PGE 1 reduced the formation of sorbitol in an ex-vivo model of diabetic cataract to an extent comparable to that attained by the known AKR inhibitor epalrestat. Taken together, these results highlight the role of PGs as AKR1B1 inhibitors and the interest in PG-related molecules as leads for the development of novel pharmacological tools.

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“…2 A number of hypotheses have been proposed to explain the pathogenic mechanism leading to diabetic complications, and the prominent theory suggests that hyperglycemia is the condition under which a significant portion of the glucose enters into the polyol pathway shown in Scheme 1. Reduction of glucose leads to accumulation of sorbitol which finally results in diabetic complications, including retinopathy, nephropathy, neuropathy and cataract.…”

Section: Introductionmentioning

confidence: 99%

Phenolic 4-hydroxy and 3,5-dihydroxy derivatives of 3-phenoxyquinoxalin-2(1H)-one as potent aldose reductase inhibitors with antioxidant activity

Zou

Qin

Hao

et al. 2015

Bioorganic & Medicinal Chemistry Letters

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Structure–activity relations on [1-(3,5-difluoro-4-hydroxyphenyl)-1H-pyrrol-3-yl]phenylmethanone. The effect of methoxy substitution on aldose reductase inhibitory activity and selectivity

Cited by 26 publications

References 39 publications

Phytochemical analysis with the antioxidant and aldose reductase inhibitory capacities of Tephrosia humilis aerial parts’ extracts

Phytochemical analysis with the antioxidant and aldose reductase inhibitory capacities of Tephrosia humilis aerial parts’ extracts

Molecular Interactions and Implications of Aldose Reductase Inhibition by PGA₁ and Clinically Used Prostaglandins

Phenolic 4-hydroxy and 3,5-dihydroxy derivatives of 3-phenoxyquinoxalin-2(1H)-one as potent aldose reductase inhibitors with antioxidant activity

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Structure–activity relations on [1-(3,5-difluoro-4-hydroxyphenyl)-1H-pyrrol-3-yl]phenylmethanone. The effect of methoxy substitution on aldose reductase inhibitory activity and selectivity

Cited by 26 publications

References 39 publications

Phytochemical analysis with the antioxidant and aldose reductase inhibitory capacities of Tephrosia humilis aerial parts’ extracts

Phytochemical analysis with the antioxidant and aldose reductase inhibitory capacities of Tephrosia humilis aerial parts’ extracts

Molecular Interactions and Implications of Aldose Reductase Inhibition by PGA1 and Clinically Used Prostaglandins

Phenolic 4-hydroxy and 3,5-dihydroxy derivatives of 3-phenoxyquinoxalin-2(1H)-one as potent aldose reductase inhibitors with antioxidant activity

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Product

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Molecular Interactions and Implications of Aldose Reductase Inhibition by PGA₁ and Clinically Used Prostaglandins