Kinetics and molecular docking studies of kaempferol and its prenylated derivatives as aldose reductase inhibitors

Abstract In diabetes, increased accumulation of sorbitol has been associated with diabetic complications through polyol pathway. Aldose reductase (AR) is one of the key factors involved in reduction of glucose to sorbitol, thereby its inhibition is considered to be important for the management of diabetic complications. In the present study, a series of seven 4-oxo-2-thioxo-1,3-thiazolidin-3-yl acetamide derivatives 3(a-g) were synthesized by the reaction of 5-(4-hydroxy-3-methoxybenzylidene)-4-oxo-2-thioxo-1,3-thiazolidin-3-yl acetic acid (2a) and 5-(4-methoxybenzylidene)-4-oxo-2-thioxo-1,3-thiazolidin-3-yl acetic acid (2b) with different amines. The synthesized compounds 3(a-g) were investigated for their in vitro aldehyde reductase (ALR1) and aldose reductase (ALR2) enzyme inhibitory potential. Compound 3c, 3d, 3e, and 3f showed ALR1 inhibition at lower micromolar concentration whereas all the compounds were more active than the standard inhibitor valproic acid. Most of the compounds were active against ALR2 but compound 3a and 3f showed higher inhibition than the standard drug sulindac. Overall the most potent compound against aldose reductase was 3f with an inhibitory concentration of 0.12 ± 0.01 µM. In vitro results showed that vanillin derivatives exhibited better activity against both aldehyde reductase and aldose reductase. The molecular docking studies were carried out to investigate the binding affinities of synthesized derivatives with both ALR1 and ALR2.

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Evaluation of antidiabetic potential of flavonoid rich fraction of Hybanthus enneaspermum in diabetic rats: In-silico molecular docking studies for aldose reductase, α-glucosidase and α-amylase

Bone Reports ◽

10.1016/j.bonr.2020.100476 ◽

2020 ◽

Vol 13 ◽

pp. 100476

Author(s):

Dinesh Kumar Patel

Keyword(s):

Molecular Docking ◽

Aldose Reductase ◽

In Silico ◽

Docking Studies ◽

Diabetic Rats ◽

Molecular Docking Studies ◽

In Silico Molecular Docking

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Exploration of Diosmin to control diabitis and its complications-an in vitro and in silico approach

Current Computer - Aided Drug Design ◽

10.2174/1573409916666200324135734 ◽

2020 ◽

Vol 16 ◽

Author(s):

Kushagra Dubey ◽

Raghvendra Dubey ◽

Revathi Gupta ◽

Arun Gupta

Keyword(s):

Molecular Docking ◽

Aldose Reductase ◽

Inhibitory Activity ◽

Blood Lipid ◽

Docking Studies ◽

Alpha Amylase ◽

Lipid Lowering ◽

Molecular Docking Studies ◽

Alpha Glucosidase

Background: Diosmin is a flavonoid obtained from the citrus fruits of the plants. Diosmin has blood lipid lowering activities, antioxidant activity, enhances venous tone and microcirculation, protects capillaries, mainly by reducing systemic oxidative stress. Objective: The present study demonstrates the potential of Diosmin against the enzymes aldose reductase, α-glucosidase, and α-amylase involved in diabetes and its complications by in vitro evaluation and reverse molecular docking studies. Method: The assay of aldose reductase was performed by using NADPH as starting material and DL-Glyceraldehyde as a substrate. DNS method was used for alpha amylase inhibition and in alpha glucosidase inhibitory activity p-nitrophenyl glucopyranoside (pNPG) was used as substrate. The reverse molecular docking studies was performed by using Molegro software (MVD) with grid resolution of 30 Å. Result: Diosmin shows potent inhibitory effect against aldose reductase (IC50:333.88±0.04 µg/mL), α-glucosidase (IC50:410.3±0.01 µg/mL) and α-amylase (IC50: 404.22±0.02 µg/mL) respectively. The standard drugs shows moderate inhibitory activity for enzymes. The MolDock Score of Diosmin was -224.127 against aldose reductase, -168.17 against α-glucosidase and -176.013 against α-amylase respectively, which was much higher than standard drugs. Conclusion: From the result it was concluded that diosmin was a potentially inhibitor of aldose reductase, alpha amylase and alpha glucosidase enzymes then the standard drugs and it will be helpful in the management of diabetes and its complications. This will also be benevolent to decrease the socio economical burden on the middle class family of the society.

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Kinetic and molecular docking studies of loganin and 7-O-galloyl-d-sedoheptulose from Corni Fructus as therapeutic agents for diabetic complications through inhibition of aldose reductase

Archives of Pharmacal Research ◽

10.1007/s12272-014-0493-3 ◽

2014 ◽

Vol 38 (6) ◽

pp. 1090-1098 ◽

Cited By ~ 8

Author(s):

Chan Mee Lee ◽

Hyun Ah Jung ◽

Sang Ho Oh ◽

Chan Hum Park ◽

Takashi Tanaka ◽

...

Keyword(s):

Molecular Docking ◽

Aldose Reductase ◽

Diabetic Complications ◽

Docking Studies ◽

Therapeutic Agents ◽

Molecular Docking Studies ◽

Corni Fructus

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In Vitro and Insilico screening platform for the identification of aldose reductase inhibitors for antidiabetic lead compounds from Abutilon indicum (L.)

10.1101/2020.10.31.363549 ◽

2020 ◽

Author(s):

L Lavanya ◽

V. Veeraraghavan ◽

CN Prashantha ◽

Renuka Srihari

Keyword(s):

Aldose Reductase ◽

Developed Countries ◽

Docking Studies ◽

Binding Interaction ◽

Reference Drug ◽

Rat Lens Aldose Reductase ◽

Aldose Reductase Inhibitors ◽

Reductase Inhibitors ◽

Abutilon Indicum

AbstractIntroductionType 2 Diabetes Mellitus (T2DM) is a long-term metabolic disorder that primarily characterized by impaired insulin resistance to become hyperglycemia. People suffering from T2DM have a higher risk of developing various diseases but, on top of that, some diabetic drugs are also suspected of increasing the risk in some cases. Aldose reductase is a key target enzyme to catalyze the reduction of glucose to sorbitol and does not readily diffuse across cell membranes and cause retinopathy and neuropathy. The aldolase reductase inhibitors prevent the conversion of glucose to sorbitol and may have the capacity of preventing and / or treating several diabetic complications. It will be expected to be twofold in the subsequent decade due to intensification in the senile population with the number of people affected, thus adding to the liability on medical providers in poor developed countries using herbal medicine to control the diabetes. In recent investigation, the antidiabetic property of phytochemicals extracted from leafs of Abutilon indicum (L.) is elucidated using animal models.Materials and MethodsIn the current study using aldose reductase enzyme assay inhibitor of Rat lens Aldose reductase were treated with A. indicum methanolic leaf extract at different concentrations (6.25, 12.5, 25, 50, 100, and 200μg/mL). Copper sulphate was used as reference drug and docking studies to predict the screen the best aldose reductase inhibitor.Results and DiscussionThe crude extract exhibited cytotoxicity against rat lens aldose reductase (IC50 = 135.8 μg/L vs ref 13.60 μg/L) using In Vitro. The docking is performed with 11 compounds shows Ertugliflozin, 9H-Cycloisolongifolene, 8-oxo and 7-hydroxy cadalene showed a good binding interaction with aldose reductase.ConclusionWe are concluding that the invitro and in silico analysis helps researchers to utilize these compound for aldose reductase inhibitors and further can be used for clinical applications.

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