Mechanism of capsaicin inhibition of aldose reductase activity

Alım, Zuhal; Kılınç, Namık; Şengül, Bülent; Beydemır, Şükrü

doi:10.1002/jbt.21898

Cited by 23 publications

(11 citation statements)

References 23 publications

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“…Many studies showed that AR is a significant pharmacological target and its inhibition can have a role in the treatment of diabetic complications . Therefore, there is a need for effective and new ARIs.…”

Section: Resultsmentioning

confidence: 99%

Antidiabetic potential: In vitro inhibition effects of bromophenol and diarylmethanones derivatives on metabolic enzymes

Demir

Taslimi

Özaslan

et al. 2018

Archiv der Pharmazie

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Aldose reductase converts glucose to sorbitol in the polyol pathway. It is an important enzyme to prevent diabetic complications. In this study, we studied the inhibitory effects of bromophenol derivatives on aldose reductase (AR), α-glucosidase, and α-amylase enzymes. In the bromophenols series, compound 1f showed the maximum inhibition effect against AR with a K i value of 0.05 ± 0.01 μM, while compound 1d showed the lowest inhibition effect against AR with a K i value of 1.13 ± 0.99 μM. In addition, α-amylase from porcine pancreas and α-glucosidase from Saccharomyces cerevisiae were used as enzymes. In this study, all compounds were tested for the inhibition of the α-glucosidase enzyme and demonstrated efficient inhibition profiles with K i values in the range of 43.62 ± 5.28 to 144.37 ± 16.37 nM against α-glucosidase.Additionally, these compounds were tested against the α-amylase enzyme, which determined an effective inhibition profile with IC 50 values in the range of 9.63-91.47 nM. These compounds can be selective inhibitors of AR, α-glucosidase, and α-amylase enzymes as antidiabetic agents. K E Y W O R D S α-amylase, α-glucosidase, aldose reductase, bromophenol, enzyme inhibition Arch Pharm Chem Life Sci. 2018;351:e1800263.wileyonlinelibrary.com/journal/ardp AR activity was assayed according to previous studies and it measured the decrease of NADPH at 340 nm spectrophotometrically. [45,46] | Enzyme purificationEnzyme purification procedures were done according to previous studies. [47,48] | Protein determinationThe protein concentration was measured according to the Bradford method by using with Coomassie Brilliant Blue G-250. [49] 4.2.7 | SDS polyacrylamide gel electrophoresisAfter the enzyme purification, the purity degree of the enzyme was controlled according to Laemmli's method [50] by using 3-8% batch sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). The electrophoresis process was carried out according to our previous papers. [51][52][53] The gel was stained with the silver staining method and photographed after staining. CONFLICT OF INTERESTThe authors declare that there are no conflicts of interest. ORCIDParham Taslimi

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Section: Resultsmentioning

confidence: 99%

Antidiabetic potential: In vitro inhibition effects of bromophenol and diarylmethanones derivatives on metabolic enzymes

Demir

Taslimi

Özaslan

et al. 2018

Archiv der Pharmazie

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“…In order to calculate Ki values of triazole derivatives showing the inhibitory effect on aldose reductase enzyme, activity values were determined with 3 different inhibitor concentrations against 5 different substrate concentrations. Lineweaver-Burk plots of each compound were drawn from the activity values obtained and Ki values and inhibition types were determined from graphics equations (Alim et al 2017;Taslimi et al 2018).…”

Section: Aldose Reductase Activity Assay and Inhibition Studiesmentioning

confidence: 99%

Synthesis, biological evaluation and molecular docking studies of new 2-ethoxy-4-{[3-alkyl(aryl)-4,5-dihydro-1H-1,2,4-triazol-5-on-4-yl]-azomethine}-phenyl benzenesulfonate derivatives on human aldose reductase enzyme

Özdemir¹,

Kılınç²,

Manap³

et al. 2021

Preprint

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A series of 2-ethoxy-4-{[3-alkyl(aryl)-4,5-dihydro-1H-1,2,4-triazol-5-on-4-yl]-azomethine}-phenyl benzenesulfonates (3) were synthesized from the reactions of 3-alkyl(aryl)-4-amino-4,5-dihydro-1H-1,2,4-triazol-5-ones (1) with 2-ethoxy-4-formyl-phenyl benzenesulfonate (2). N-acetyl derivatives (4) of compounds 3 were also obtained. Then, the compounds 3 have been treated with morpholine and 2,6-dimethylmorpholine in the presence of formaldehyde to synthesize 2-ethoxy-4-{[1-(morpholine-4-yl-methyl)-3-alkyl(aryl)-4,5-dihydro-1H-1,2,4-triazol-5-on-4-yl]-azomethine}-phenyl benzenesulfonates (5) and 2-ethoxy-4-{[1-(2,6-dimethylmorpholine-4-yl-methyl)-3-alkyl(aryl)-4,5-dihydro-1H-1,2,4-triazol-5-on-4-yl]-azomethine}-phenyl benzenesulfonates (6), respectively. The structures of twenty-six new compounds were identified by using elemental analysis, IR, 1H NMR, 13C NMR, and MS spectral data. In addition, in vitro antibacterial activities of the new compounds were evaluated against six bacteria such as Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Bacillus subtilis, Bacillus cereus and Klepsiella pneumonia according to agar well diffusion method. Furthermore, in order to determine the possible antidiabetic properties of the synthesized 1,2,4-triazole derivatives, inhibition effects on the AR enzyme were investigated and molecular docking studies were carried out to determine the receptor-ligand interactions of these compounds. IC50 values of triazole-derived compounds (6a, 6b, 6d-g) against AR enzyme were determined as 0.95 µM, 0.75 µM, 1.83 µM, 0.62 µM, 1.05 µM, 1.06 µM, respectively. Considering the docking scores and binding energies obtained docking studies, it has been shown that molecules fit very well to the active site of the AR enzyme.

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“…Diabetes mellitus (DM) is a global metabolic disease accompanied by hyperglycemia and glucose metabolic dysfunction, and it has been estimated that nearly 642 million individuals will develop diabetes by 2040. 1 Aldose reductase (AR, AKR1B1; EC 1.1.1.21) is a polyol pathway enzyme 2 whose overexpression in DM leads to diabetic consequences such as neuropathy, 3 retinopathy, 4 cataracts, 5 nephropathy, 6 and cardiovascular diseases. 7 Therefore, inhibiting AR is among the most important drug targets (Figure 1).…”

Section: Introductionmentioning

confidence: 99%

N‐substituted phthalazine sulfonamide derivatives as non‐classical aldose reductase inhibitors

Türkeş

Arslan

Demir

et al. 2022

J of Molecular Recognition

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Aldose reductase (AR, AKR1B1; EC 1.1.1.21) is an aldo‐keto reductase that has been widely investigated as an enzyme crucially involved in the pathogenesis of several chronic complications, including nephropathy, neuropathy, retinopathy, and cataracts associated with diabetes mellitus. Although sulfonamides have been reported to possess many other biological activities, in continuation of our interest in designing and discovering potent inhibitors of AR, herein, we have evaluated the AR inhibitory potential of N‐substituted phthalazine sulfonamide derivatives 5a‐l. The biological studies revealed that all the derivatives show excellent activity against AR, with KI constants ranging from 67.73 to 495.20 nM. Among these agents, 4‐(6‐nitro‐1,4‐dioxo‐1,2,3,4‐tetrahydrophthalazine‐2‐carbonyl)benzenesulfonamide (5e) and 1,4‐dioxo‐3‐(4‐sulfamoylbenzoyl)‐1,2,3,4‐tetrahydrophthalazine‐6‐carboxylic acid (5f) showed prominent inhibitory activity with KI values of 67.73 and 148.20 nM, respectively, vs AR and were found to be more potent than epalrestat (KI = 852.50 nM), the only AR inhibitor currently used in the therapy. Moreover, molecular docking studies were also performed to rationalize binding site interactions of these sulfonamides (5a‐l) with the target enzyme AR. According to ADME‐Tox, predicts were also determined that these derivatives be ARIs displaying suitable drug‐like properties. The sulfonamides identified in this study may be used to develop lead therapeutic agents inhibiting diabetic complications.

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Mechanism of capsaicin inhibition of aldose reductase activity

Cited by 23 publications

References 23 publications

Antidiabetic potential: In vitro inhibition effects of bromophenol and diarylmethanones derivatives on metabolic enzymes

Antidiabetic potential: In vitro inhibition effects of bromophenol and diarylmethanones derivatives on metabolic enzymes

Synthesis, biological evaluation and molecular docking studies of new 2-ethoxy-4-{[3-alkyl(aryl)-4,5-dihydro-1H-1,2,4-triazol-5-on-4-yl]-azomethine}-phenyl benzenesulfonate derivatives on human aldose reductase enzyme

N‐substituted phthalazine sulfonamide derivatives as non‐classical aldose reductase inhibitors

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