The Discovery of Potential MDM2 Inhibitors: A Combination of Pharmacophore Modeling, Virtual Screening, Molecular Docking Studies and In Vitro/In Vivo Biological Evaluation

ChemMedChem ◽  
2021 ◽  
Author(s):  
Xuelin Zhang ◽  
Chunqiao Zhou ◽  
Yang Yang ◽  
Hailin Liu ◽  
Song Wang ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Virtual Screening ◽  
Pharmacophore Modeling ◽  
Docking Studies ◽  
Biological Evaluation ◽  
Molecular Docking Studies

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>

Evaluation of anti-diabetic and alpha glucosidase inhibitory action of anthraquinones from Rheum emodi

2015 ◽  
Vol 6 (8) ◽  
pp. 2693-2700 ◽  
Author(s):  
Aditya Arvindekar ◽  
Tanaji More ◽  
Pavan V. Payghan ◽  
Kirti Laddha ◽  
Nanda Ghoshal ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Inhibitory Action ◽  
Docking Studies ◽  
Molecular Docking Studies ◽  
Alpha Glucosidase

The 1,8-dihydroxyanthraquinones from the culinary and medicinally important plant Rheum emodi exert anti-hyperglycemic potential but notably different α-glucosidase actions as established by in vitro, in vivo, kinetics and molecular docking studies.

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.

Evaluation of Antiplasmodial Potential of C2 and C8 Modified Quinolines: in vitro and in silico Study

2019 ◽  
Vol 15 (7) ◽  
pp. 790-800 ◽  
Author(s):  
Rakesh Kumar ◽  
Ritika Sharma ◽  
Inder Kumar ◽  
Pooja Upadhyay ◽  
Ankit Kumar Dhiman ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Malaria Parasite ◽  
Resistance Index ◽  
Microtiter Plate ◽  
Docking Studies ◽  
Biological Evaluation ◽  
Molecular Docking Studies ◽  
Human Red Blood Cells ◽  
Computational Molecular Docking

Background: Malaria remains a common life-threatening infectious disease across the globe due to the development of resistance by Plasmodium parasite against most antimalarial drugs. The situation demands new and effective drug candidates against Plasmodium. Objectives: The objective of this study is to design, synthesize and test novel quinoline based molecules against the malaria parasite. Methods: C2 and C8 modified quinoline analogs obtained via C-H bond functionalization approach were synthesized and evaluated for inhibition of growth of P. falciparum grown in human red blood cells using SYBR Green microtiter plate based screening. Computational molecular docking studies were carried out with top fourteen molecules using Autodoc software. Results: The biological evaluation results revealed good activity of quinoline-8-acrylate 3f (IC50 14.2 µM), and the 2-quinoline-α-hydroxypropionates 4b (IC50 6.5 µM), 4j (IC50 5.5 µM) and 4g (IC50 9.5 µM), against chloroquine sensitive Pf3D7 strain. Top fourteen molecules were screened also against chloroquine resistant Pf INDO strain and the observed resistant indices were found to lie between 1 and 7.58. Computational molecular docking studies indicated a unique mode of binding of these quinolines to Falcipain-2 and heme moiety, indicating these to be the probable targets of their antiplasmodial action. Conclusion: An important finding of our work is the fact that unlike Chloroquine which shows a resistance Index of 15, the resistance indices for the most promising molecules studied by us were about one indicating equal potency against drug sensitive and resistant strains of the malaria parasite.

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