scholarly journals Molecular docking studies of α-mangostin, γ-mangostin, and xanthone on peroxisome proliferator-activated receptor gamma diphenyl peptidase-4 enzyme, and aldose reductase enzyme as an antidiabetic drug candidate

2021 ◽  
Vol 12 (2) ◽  
pp. 196
Author(s):  
Rifa'atul Mahmudah ◽  
IKetut Adnyana ◽  
ElinYulinah Sukandar
Keyword(s):  
Molecular Docking ◽  
Aldose Reductase ◽  
Docking Studies ◽  
Drug Candidate ◽  
Peroxisome Proliferator ◽  
Antidiabetic Drug ◽  
Peroxisome Proliferator Activated Receptor ◽  
Molecular Docking Studies

scholarly journals In silico molecular docking studies of some phytochemicals against peroxisome-proliferator activated receptor gamma (PPAR-γ)

2018 ◽  
Vol 5 (2) ◽  
pp. 001-005
Author(s):  
H. A. Ahmed ◽  
I. Y. Alkali
Keyword(s):  
Molecular Docking ◽  
Insulin Sensitivity ◽  
Binding Affinity ◽  
Docking Studies ◽  
Peroxisome Proliferator ◽  
Autodock Vina ◽  
Peroxisome Proliferator Activated Receptor ◽  
Standard Drug ◽  
Molecular Docking Studies ◽  
Ppar Γ

Peroxisome Proliferator-Activated Receptor-γ (PPAR-γ) is a ligand-activated transcription factor and a member of the nuclear receptor superfamily that regulate the gene expression of proteins involved in glucose, lipid metabolism, adipocyte proliferation and differentiation and insulin sensitivity. Thiazolidinediones (TZDs) are one important class of synthetic agonists of PPAR-γ. TZDs are antidiabetic agents that target adipose tissue and improve insulin sensitivity, and they are currently being used in the treatment of type 2 diabetes. The study was carried out in order to discover new phytochemicals that have the ability to stimulate the PPAR-γ using molecular docking studies. AutoDock vina was used as molecular-docking tool in order to carry out the docking simulations. Nine phytochemicals namely plumbagin, quercetin, isovitexin, mangiferin, syringin, lupe-20-ene-3-one, purine 2, 6-dione, diosmetin and β sitosterol and pioglitazone a standard drug were docked against PPAR-γ using AutoDock vina and the results were analyzed using binding affinity. The results revealed that the compounds have significant binding affinity towards the PPAR-γ comparable to pioglitazone the standard drug. Based on the findings of this study these phytochemicals can serve as source of antidiabetic drugs via the mechanism of inhibition of PPAR-γ.

scholarly journals Design and synthesis of novel heterocyclic compounds as a PPAR-γ agonist

2020 ◽  
Vol 11 (2) ◽  
pp. 2063-2069
Author(s):  
Zambare Y. B. ◽  
Bhole R. P. ◽  
Chitlange S. S.
Keyword(s):  
Diabetes Mellitus ◽  
Molecular Docking ◽  
Docking Studies ◽  
Binding Energies ◽  
Oral Glucose ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Molecular Docking Studies ◽  
Discovery Studio ◽  
Ppar Γ

The multifarious metabolic syndrome, diabetes mellitus (DM), is a diseaseof concern all over the world and is approximate to affect 400 million individuals by the 2020. Several classes of drugs at the moment are available to lessen hyperglycemia in diabetes mellitus especially in Type-II. These drugs mostly have dangerous side effects and thus incisive for a new class of compounds is necessary to conquer this inconvenience. A series of 6 novel 5-nitrobenzofuran-2yl-carbamides derivatives were synthesized and molecular docking studies were performed on PPAR-γ target using (PDB code-4rfm).The preparation of5-nitro-1-benzofuran-2-carbohydrazide(4) on action with acetic acid, 1, 4-diaxone and sodium nitrite resulted in 5-nitro-1-benzofuran-2-carbonyl azide (5).The related compound (5) on action with substituted aromatic substituted amines undergoes Curtis type of rearrangement to give 5-nitro-N-(sub. carbamoyl)-1-benzofuran-2-carboxamide.The characterization and identification of prepared compounds were identified on the basis of NMR, IR, Mass and elemental analysis. Docking study of targeted compounds were done using software Autodock Tools 1.5.6 and visualisation done by Discovery Studio 3.5 software (Accelrys Inc. San Diego, CA USA). Molecular docking studies, the binding energies are determined to be in the range of –5.90 to –9.80 kcal/mol, with peroxisome proliferator activated receptor γ (PPAR-γ) receptors (PDB ID: 4RFM). The prepared compounds have been studied for their oral glucose tolerance test to distinguish the effect on plasma glucose level.

scholarly journals Hypoglycemic, hepatoprotective and molecular docking studies of 5-[(4-chlorophenoxy) methyl]-1, 3, 4-oxadiazole-2-thiol

2018 ◽  
Vol 13 (2) ◽  
pp. 149 ◽  
Author(s):  
Naureen Shehzadi ◽  
Khalid Hussain ◽  
Nadeem Irfan Bukhari ◽  
Muhammad Islam ◽  
Muhammad Tanveer Khan ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Video Clip ◽  
Serum Levels ◽  
Docking Studies ◽  
Normal Serum ◽  
Yeast Cells ◽  
Drug Candidate ◽  
Molecular Docking Studies

<p class="Abstract">The present study aimed at the evaluation of anti-hyperglycemic and hepatoprotective potential of a new drug candidate, 5-[(4-chlorophenoxy) methyl]-1,3,4-oxadiazole-2-thiol (OXCPM) through in vitro and in vivo assays, respectively. The compound displayed excellent dose-dependent ɑ-amylase (28.0-92.0%), ɑ-glucosidase (40.3-93.1%) and hemoglobin glycosylation (9.0%-54.9%) inhibitory effects and promoted the uptake of glucose by the yeast cells (0.2 to 26.3%). The treatment of the isoniazid- and rifampicin- (p.o., 50 mg/kg of each) intoxicated rats with OXCPM (100 mg/kg, p.o.) resulted in restoring the normal serum levels of the non-enzymatic (total bilirubin, total protein and albumin) and bringing about a remarkable decrease in the levels of enzymatic (alanine transaminases, aspartate transaminases and alkaline phosphatase) biomarkers. The molecular docking studies indicated high binding affinity of the compound for hyperglycemia-related protein targets; fructose-1,6-bisphosphatase, beta<sub>2</sub>-adrenergic receptors and glucokinase. The results indicate that OXCPM may not only reduce hyperglycemia by enzyme inhibition but also the disease complications through protection of hemoglobin glycosylation and hepatic injury.</p><p class="Abstract"><strong>Video Clip of Methodology:</strong></p><p class="Abstract">Glucose uptake by yeast cells:   4 min 51 sec   <a href="https://www.youtube.com/v/8cJkuMtV0Wc">Full Screen</a>   <a href="https://www.youtube.com/watch?v=8cJkuMtV0Wc">Alternate</a></p>

scholarly journals Multi-Targeted Molecular Docking, Pharmacokinetics, and Drug-Likeness Evaluation of Okra-Derived Ligand Abscisic Acid Targeting Signaling Proteins Involved in the Development of Diabetes

Molecules ◽  
2021 ◽  
Vol 26 (19) ◽  
pp. 5957
Author(s):  
Syed Amir Ashraf ◽  
Abd Elmoneim O. Elkhalifa ◽  
Khalid Mehmood ◽  
Mohd Adnan ◽  
Mushtaq Ahmad Khan ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Abscisic Acid ◽  
Molecular Docking ◽  
Binding Energy ◽  
Age Groups ◽  
Ppar Gamma ◽  
Inhibition Constant ◽  
Drug Candidate ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor

Diabetes mellitus is a global threat affecting millions of people of different age groups. In recent years, the development of naturally derived anti-diabetic agents has gained popularity. Okra is a common vegetable containing important bioactive components such as abscisic acid (ABA). ABA, a phytohormone, has been shown to elicit potent anti-diabetic effects in mouse models. Keeping its anti-diabetic potential in mind, in silico study was performed to explore its role in inhibiting proteins relevant to diabetes mellitus- 11β-hydroxysteroid dehydrogenase (11β-HSD1), aldose reductase, glucokinase, glutamine-fructose-6-phosphate amidotransferase (GFAT), peroxisome proliferator-activated receptor-gamma (PPAR-gamma), and Sirtuin family of NAD(+)-dependent protein deacetylases 6 (SIRT6). A comparative study of the ABA-protein docked complex with already known inhibitors of these proteins relevant to diabetes was compared to explore the inhibitory potential. Calculation of molecular binding energy (ΔG), inhibition constant (pKi), and prediction of pharmacokinetics and pharmacodynamics properties were performed. The molecular docking investigation of ABA with 11-HSD1, GFAT, PPAR-gamma, and SIRT6 revealed considerably low binding energy (ΔG from −8.1 to −7.3 Kcal/mol) and predicted inhibition constant (pKi from 6.01 to 5.21 µM). The ADMET study revealed that ABA is a promising drug candidate without any hazardous effect following all current drug-likeness guidelines such as Lipinski, Ghose, Veber, Egan, and Muegge.

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

2012 ◽  
Vol 197 (2-3) ◽  
pp. 110-118 ◽  
Author(s):  
Hyun Ah Jung ◽  
Hye Eun Moon ◽  
Sang Ho Oh ◽  
Byung-Woo Kim ◽  
Hee Sook Sohn ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Aldose Reductase ◽  
Docking Studies ◽  
Molecular Docking Studies ◽  
Aldose Reductase Inhibitors ◽  
Reductase Inhibitors

scholarly journals Rhodanine-3-Acetamide Derivatives as Aldose and Aldehyde Reductase Inhibitors to Treat Diabetic Complications; Synthesis, Biological Evaluation and Molecular Docking Studies

2020 ◽  
Author(s):  
Mohsinul Mulk Bacha ◽  
Humaira Nadeem ◽  
Shafiq Ur Rehman ◽  
Sadia Sarwar ◽  
Aqeel Imran ◽  
...  
Keyword(s):  
Acetic Acid ◽  
Molecular Docking ◽  
Aldose Reductase ◽  
Diabetic Complications ◽  
Docking Studies ◽  
Biological Evaluation ◽  
Aldehyde Reductase ◽  
Standard Drug ◽  
Molecular Docking Studies

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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