scholarly journals Pharmacophore Modeling and Molecular Docking Studies on Pinus roxburghii as a Target for Diabetes Mellitus

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Pawan Kaushik ◽  
Sukhbir Lal Khokra ◽  
A. C. Rana ◽  
Dhirender Kaushik
Keyword(s):  
Molecular Docking ◽  
Aldose Reductase ◽  
Pharmacophore Model ◽  
Docking Studies ◽  
Antidiabetic Activity ◽  
Bioactive Constituents ◽  
Active Constituent ◽  
Pinus Roxburghii ◽  
Molecular Docking Studies ◽  
Active Target

The present study attempts to establish a relationship between ethnopharmacological claims and bioactive constituents present in Pinus roxburghii against all possible targets for diabetes through molecular docking and to develop a pharmacophore model for the active target. The process of molecular docking involves study of different bonding modes of one ligand with active cavities of target receptors protein tyrosine phosphatase 1-beta (PTP-1β), dipeptidyl peptidase-IV (DPP-IV), aldose reductase (AR), and insulin receptor (IR) with help of docking software Molegro virtual docker (MVD). From the results of docking score values on different receptors for antidiabetic activity, it is observed that constituents, namely, secoisoresinol, pinoresinol, and cedeodarin, showed the best docking results on almost all the receptors, while the most significant results were observed on AR. Then, LigandScout was applied to develop a pharmacophore model for active target. LigandScout revealed that 2 hydrogen bond donors pointing towards Tyr 48 and His 110 are a major requirement of the pharmacophore generated. In our molecular docking studies, the active constituent, secoisoresinol, has also shown hydrogen bonding with His 110 residue which is a part of the pharmacophore. The docking results have given better insights into the development of better aldose reductase inhibitor so as to treat diabetes related secondary complications.

scholarly journals IN SILICO STUDIES ON FUNCTIONALIZED AZAGLYCINE DERIVATIVES CONTAINING 2, 4-THIAZOLIDINEDIONE SCAFFOLD ON MULTIPLE TARGETS

2017 ◽  
Vol 9 (8) ◽  
pp. 209 ◽  
Author(s):  
Arifa Begum ◽  
Shaheen Begum ◽  
Prasad Kvsrg ◽  
Bharathi K.
Keyword(s):  
Molecular Docking ◽  
Oral Bioavailability ◽  
In Silico ◽  
Viral Infections ◽  
Target Prediction ◽  
Docking Studies ◽  
Antidiabetic Activity ◽  
Molecular Docking Studies ◽  
In Silico Studies ◽  
Glycine Derivative

Objective: The 2, 4-thiazolidinedione containing compounds could lead to most promising scaffolds with higher efficiency toward the targets recognized for its antidiabetic activity when combined with azaglycine moiety. The objective of the present work was to merge functionalized aza glycines with 2, 4-thiazolidinediones, perform in silico evaluation by molecular properties prediction and undertake the molecular docking studies with targets relevant to diabetes, bacterial and viral infections using Swiss Dock programme for unraveling the target identification which can be used for further designing.Methods: (i) In silico studies were performed using Molinspiration online tool, Swiss ADME website and Swiss Target Prediction websites to compute the physicochemical descriptors, oral bioavailability and brain penetration. (ii) Molecular docking studies were performed using Swiss Dock web service for enumeration of binding affinities and assess their biological potentiality.Results: The results predicted good drug likeness, solubility, permeability and oral bioavailability for the compounds. All the compounds showed good docking scores as compared to the reference drugs. The N-oleoyl functionalized aza glycine derivative demonstrated superior binding properties towards all the studied target reference proteins, suggesting its significance in pharmacological actions.Conclusion: The binding interactions observed in the molecular docking studies suggest good binding affinity of the oleoyl functionalized aza glycine derivative, indicating that this derivative would be a promising lead for further investigations of anti-viral, anti-inflammatory and anti-diabetic activities.

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 A new class of potential antidiabetic acetohydrazides: Synthesis, in vivo antidiabetic activity and molecular docking studies

2017 ◽  
Vol 12 (3) ◽  
pp. 319 ◽  
Author(s):  
Mubeen Arif ◽  
Furukh Jabeen ◽  
Aamer Saeed ◽  
Irfan Zia Qureshi ◽  
Nadia Mushtaq
Keyword(s):  
Molecular Docking ◽  
Video Clip ◽  
Docking Studies ◽  
Antidiabetic Activity ◽  
Molecular Docking Studies ◽  
H Nmr ◽  
New Class ◽  
Full Screen ◽  
Pharmacologically Active

<p class="Abstract">Two new pharmacologically active series of tetrazolopyridine-acetohydrazide conjugates [9 (a-n), 10 (a-n)] were synthesized by reacting a variety of suitably substituted benzaldehydes and isomeric 2-(5-(pyridin-3/4-yl)-2H-tetrazol-2-yl)acetohydrazides (7, 8). The synthesized compounds were analyzed through FTIR, <sup>1</sup>H NMR, <sup>13</sup>C NMR and elemental techniques. These acetohydrazides were screened for their in vivo antidiabetic activity and molecular docking studies. An excellent agreement was obtained as the best docked poses show-ed important binding features mostly based on interactions due to an oxygen atom and aromatic moieties of the series. The compounds 9a, 9c and 10l were found to be the most active in lowering blood glucose, having the potential of being good antidiabetic agents.</p><p><strong>Video Clip of Methodology</strong>:</p><p>Synthesis of 3/4-(2H-tetrazole-5-yl)pyridine: 1 min 57 sec   <a href="https://www.youtube.com/v/CHp8HxlEa2M">Full Screen</a>   <a href="https://www.youtube.com/watch?v=CHp8HxlEa2M">Alternate</a></p>

scholarly journals Discovery of Small Molecules that Target Vascular Endothelial Growth Factor Receptor-2 Signalling Pathway Employing Molecular Modelling Studies

Cells ◽  
2019 ◽  
Vol 8 (3) ◽  
pp. 269 ◽  
Author(s):  
Shailima Rampogu ◽  
Ayoung Baek ◽  
Chanin Park ◽  
Shraddha Parate ◽  
Saravanan Parameswaran ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Molecular Docking ◽  
Growth Factor ◽  
Growth Factor Receptor ◽  
Pharmacophore Model ◽  
Docking Studies ◽  
Vascular Endothelial ◽  
Molecular Docking Studies ◽  
Angiogenic Inhibitors ◽  
Endothelial Growth Factor

Angiogenesis is defined as the formation of new blood vessels and is a key phenomenon manifested in a host of cancers during which tyrosine kinases play a crucial role. Vascular endothelial growth factor receptor-2 (VEGFR-2) is pivotal in cancer angiogenesis, which warrants the urgency of discovering new anti-angiogenic inhibitors that target the signalling pathways. To obtain this objective, a structure-based pharmacophore model was built from the drug target VEGFR-2 (PDB code: 4AG8), complexed with axitinib and was subsequently validated and employed as a 3D query to retrieve the candidate compounds with the key inhibitory features. The model was escalated to molecular docking studies resulting in seven candidate compounds. The molecular docking studies revealed that the seven compounds displayed a higher dock score than the reference-cocrystallised compound. The GROningen MAchine for Chemical Simulations (GROMACS) package guided molecular dynamics (MD) results determined their binding mode and affirmed stable root mean square deviation. Furthermore, these compounds have preserved their key interactions with the residues Glu885, Glu917, Cys919 and Asp1046. The obtained findings deem that the seven compounds could act as novel anti-angiogenic inhibitors and may further assist as the prototype in designing and developing new 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.

Mechanochemical Synthesis, in vitro Evaluation and Molecular Docking Studies of 4-Amino-2-arylamino-5-(benzofuran-2-oyl)thiazoles as Antidiabetic Agents

2019 ◽  
Vol 16 (7) ◽  
pp. 560-568
Author(s):  
Vijayan R. Akhila ◽  
Maheswari R. Priya ◽  
Daisy R. Sherin ◽  
Girija K. Krishnapriya ◽  
Sreerekha V. Keerthi ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Mechanochemical Synthesis ◽  
Active Sites ◽  
Docking Studies ◽  
Binding Energies ◽  
Antidiabetic Activity ◽  
Antidiabetic Agents ◽  
Molecular Docking Studies ◽  
Ic50 Value

The synthesis of 4-amino-2-arylamino-5-(benzofuran-2-oyl)thiazoles 4a-h, as example of 2,4-diaminothiazole-benzofuran hybrids and an evaluation of their antidiabetic activity, by in vitro and computational methods, are reported. The synthesis of these diaminothiazoles was achieved mechano chemically by a rapid solvent-less method. Their antidiabetic activity was assessed by &#945;-glucosidase and &#945;-amylase inhibition assays. The, IC50 value for &#945;-glucosidase inhibition by 4-amino-5- (benzofuran-2-oyl)-2-(4-methoxyphenylamino)thiazole (4d) was found to be 20.04 &#181;M and the IC50 value for &#945;-amylase inhibition, 195.03 &#181;M, whereas the corresponding values for reference acarbose were 53.38 &#181;M and 502.03 &#181;M, respectively. Molecular docking studies at the active sites of &#945;- glucosidase and α-amylase showed that among the diaminothiazoles 4a-h now studied, 4-amino-5- (benzofuran-2-oyl)-2-(4-methoxyphenylamino)thiazole (4d) has the highest D-scores of -8.63 and -8.08 for &#945;-glucosidase and for α-amylase, with binding energies -47.76 and -19.73 kcal/mol, respectively.

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