scholarly journals Pharmacophore-driven Identification of N-Methyl-D-Receptor Antagonists as Potent Neuroprotective Agents Validated Using In-Vivo Studies

2018 ◽  
Author(s):  
Mukta Sharma ◽  
Anupama Mittal ◽  
Aarti Singh ◽  
Ashwin K. Jainarayanan ◽  
Swapnil Sharma ◽  
...  
Keyword(s):  
Nmda Receptor ◽  
Virtual Screening ◽  
Learning And Memory ◽  
Three Dimensional ◽  
Scoring Function ◽  
The Elderly ◽  
Structural Features ◽  
In Vivo Studies ◽  
Receptor Antagonists

AbstractAlzheimer’s disease (AD), the most widespread cause of dementia is delineated by progressive cognitive impairment in the elderly people. During its progression, N-Methyl-D-Aspartate receptor antagonists are known to play a key role in the mechanisms of learning and memory. Extensive side effects alongside other effects on learning and memory have limited the therapeutic significance of various blockers and antagonists of the NMDA receptor. In this study, we identify potential compounds targeted against NMDA. In order to reveal the essential structural features for NMDA receptor, three-dimensional pharmacophore models are constructed based on a set of known NMDA inhibitors. This is followed by virtual screening which results in novel chemical compounds having the potential to inhibit NMDA. The lead compounds are then subjected to molecular docking and assessed by a scoring function, which results in two compounds with high Libdock scores. These compounds also show interactions with important residues at the active site. The compounds are shortlisted on the basis of high estimated activity, fit values, LibDock score, no violation to Lipinski’s and availability for procuring.Of the shortlisted compounds, one compound satisfying the entire aforementioned criterion is further tested using in-vivo studies on mice with the help of an eight-arm radial maze. The pharmacophore-based virtual screening protocol presented in this study pave the way forward to address the unmet medical need of Alzheimer disease.

Promising Anti-stroke Signature of Voglibose: Investigation through In- Silico Molecular Docking and Virtual Screening in In-Vivo Animal Studies

2020 ◽  
Vol 20 (3) ◽  
pp. 223-235
Author(s):  
Pooja Shah ◽  
Vishal Chavda ◽  
Snehal Patel ◽  
Shraddha Bhadada ◽  
Ghulam Md. Ashraf
Keyword(s):  
Molecular Docking ◽  
Virtual Screening ◽  
In Silico ◽  
Reductase Activity ◽  
Infarct Volume ◽  
Docking Studies ◽  
Serum Glucose ◽  
In Vivo Studies ◽  
In Silico Molecular Docking

Background: Postprandial hyperglycemia considered to be a major risk factor for cerebrovascular complications. Objective: The current study was designed to elucidate the beneficial role of voglibose via in-silico in vitro to in-vivo studies in improving the postprandial glycaemic state by protection against strokeprone type 2 diabetes. Material and Methods: In-Silico molecular docking and virtual screening were carried out with the help of iGEMDOCK+ Pymol+docking software and Protein Drug Bank database (PDB). Based on the results of docking studies, in-vivo investigation was carried out for possible neuroprotective action. T2DM was induced by a single injection of streptozotocin (90mg/kg, i.v.) to neonates. Six weeks after induction, voglibose was administered at the dose of 10mg/kg p.o. for two weeks. After eight weeks, diabetic rats were subjected to middle cerebral artery occlusion, and after 72 hours of surgery, neurological deficits were determined. The blood was collected for the determination of serum glucose, CK-MB, LDH and lipid levels. Brains were excised for determination of brain infarct volume, brain hemisphere weight difference, Na+-K+ ATPase activity, ROS parameters, NO levels, and aldose reductase activity. Results: In-silico docking studies showed good docking binding score for stroke associated proteins, which possibly hypotheses neuroprotective action of voglibose in stroke. In the present in-vivo study, pre-treatment with voglibose showed a significant decrease (p<0.05) in serum glucose and lipid levels. Voglibose has shown significant (p<0.05) reduction in neurological score, brain infarct volume, the difference in brain hemisphere weight. On biochemical evaluation, treatment with voglibose produced significant (p<0.05) decrease in CK-MB, LDH, and NO levels in blood and reduction in Na+-K+ ATPase, oxidative stress, and aldose reductase activity in brain homogenate. Conclusion: In-silico molecular docking and virtual screening studies and in-vivo studies in MCAo induced stroke, animal model outcomes support the strong anti-stroke signature for possible neuroprotective therapeutics.

scholarly journals Three-Dimensional Zirconia-Based Scaffolds for Load-Bearing Bone-Regeneration Applications: Prospects and Challenges

Materials ◽  
2021 ◽  
Vol 14 (12) ◽  
pp. 3207
Author(s):  
Kumaresan Sakthiabirami ◽  
Vaiyapuri Soundharrajan ◽  
Jin-Ho Kang ◽  
Yunzhi Peter Yang ◽  
Sang-Won Park
Keyword(s):  
Bone Regeneration ◽  
Biological Activities ◽  
Three Dimensional ◽  
In Vivo Studies ◽  
High Mechanical Strength ◽  
Real World Applications ◽  
3D Fabrication ◽  
Dental Applications

The design of zirconia-based scaffolds using conventional techniques for bone-regeneration applications has been studied extensively. Similar to dental applications, the use of three-dimensional (3D) zirconia-based ceramics for bone tissue engineering (BTE) has recently attracted considerable attention because of their high mechanical strength and biocompatibility. However, techniques to fabricate zirconia-based scaffolds for bone regeneration are in a stage of infancy. Hence, the biological activities of zirconia-based ceramics for bone-regeneration applications have not been fully investigated, in contrast to the well-established calcium phosphate-based ceramics for bone-regeneration applications. This paper outlines recent research developments and challenges concerning numerous three-dimensional (3D) zirconia-based scaffolds and reviews the associated fundamental fabrication techniques, key 3D fabrication developments and practical encounters to identify the optimal 3D fabrication technique for obtaining 3D zirconia-based scaffolds suitable for real-world applications. This review mainly summarized the articles that focused on in vitro and in vivo studies along with the fundamental mechanical characterizations on the 3D zirconia-based scaffolds.

scholarly journals The Challenging Melanoma Landscape: From Early Drug Discovery to Clinical Approval

Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 3088
Author(s):  
Mariana Matias ◽  
Jacinta O. Pinho ◽  
Maria João Penetra ◽  
Gonçalo Campos ◽  
Catarina Pinto Reis ◽  
...  
Keyword(s):  
Therapeutic Potential ◽  
Drug Evaluation ◽  
Three Dimensional ◽  
Experimental Models ◽  
In Vivo Studies ◽  
Murine Models ◽  
In Vivo Experiments ◽  
Novel Therapeutic Strategies

Melanoma is recognized as the most dangerous type of skin cancer, with high mortality and resistance to currently used treatments. To overcome the limitations of the available therapeutic options, the discovery and development of new, more effective, and safer therapies is required. In this review, the different research steps involved in the process of antimelanoma drug evaluation and selection are explored, including information regarding in silico, in vitro, and in vivo experiments, as well as clinical trial phases. Details are given about the most used cell lines and assays to perform both two- and three-dimensional in vitro screening of drug candidates towards melanoma. For in vivo studies, murine models are, undoubtedly, the most widely used for assessing the therapeutic potential of new compounds and to study the underlying mechanisms of action. Here, the main melanoma murine models are described as well as other animal species. A section is dedicated to ongoing clinical studies, demonstrating the wide interest and successful efforts devoted to melanoma therapy, in particular at advanced stages of the disease, and a final section includes some considerations regarding approval for marketing by regulatory agencies. Overall, considerable commitment is being directed to the continuous development of optimized experimental models, important for the understanding of melanoma biology and for the evaluation and validation of novel therapeutic strategies.

scholarly journals Potential anticancer activity of curcumin analogs containing sulfone on human cancer cells

2016 ◽  
Vol 68 (1) ◽  
pp. 125-133 ◽  
Author(s):  
Qiuyan Zhang ◽  
Dongli Li ◽  
Yue Liu ◽  
Hui Wang ◽  
Changyuan Zhang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Human Cancer ◽  
Three Dimensional ◽  
In Vivo Studies ◽  
Anticancer Activities ◽  
Human Cancer Cells ◽  
Curcumin Analogs ◽  
Phosphorylated Akt ◽  
Transcription 3

Three curcumin analogs(S1-S3) containing sulfone were investigated for their effects on human prostate cancer PC-3, colon cancer HT-29, lung cancer H1299 and pancreatic cancer BxPC-3 cells. The three compounds were approximately 16-to 96-fold more active than curcumin in these cell lines as determined by the MTT assay. The effects of these compounds on cell growth were further studied in prostate cancer PC-3 cells in both two dimensional (2D) and three dimensional (3D) cultures. S1-S3strongly inhibited the growth and induced cell death in PC-3 cells, and the effects of these compounds were associated with suppression of nuclear factor kappa B (NF-?B) transcriptional activity. Moreover, treatment of PC-3 cells with all three compounds caused a decrease in the level of phosphorylated signal transducer and activator of transcription-3 (p-STAT3) (Tyr705),but not p-STAT3(Ser727). Only S1and S2decreased the presence of phosphorylated Akt (p-Akt) in PC-3 cells. These curcumin analogs warrant further in vivo studies for anticancer activities in suitable animal models.

scholarly journals NMDA receptor antagonists ketamine and Ro25-6981 inhibit evoked release of glutamate in vivo in the subiculum

2014 ◽  
Vol 4 (6) ◽  
pp. e395-e395 ◽  
Author(s):  
T L Stan ◽  
A Alvarsson ◽  
N Branzell ◽  
V C Sousa ◽  
P Svenningsson
Keyword(s):  
Nmda Receptor ◽  
Nmda Receptor Antagonists ◽  
Receptor Antagonists

Identifying the structural features and diversifying the chemical domain of peripherally acting CB1 receptor antagonists using molecular modeling techniques

RSC Advances ◽  
2016 ◽  
Vol 6 (2) ◽  
pp. 1466-1483 ◽  
Author(s):  
Mayank Kumar Sharma ◽  
Prashant R. Murumkar ◽  
Guanglin Kuang ◽  
Yun Tang ◽  
Mange Ram Yadav
Keyword(s):  
Molecular Modeling ◽  
Virtual Screening ◽  
3D Qsar ◽  
Structural Features ◽  
Cb1 Receptor ◽  
Receptor Antagonists ◽  
Modeling Techniques ◽  
Qsar Models ◽  
Cb1 Receptor Antagonists

A four featured pharmacophore and predictive 3D-QSAR models were developed which were used for virtual screening of the Asinex database to get chemically diverse hits of peripherally active CB1 receptor antagonists.

The Effect of Angle and Flow Rate Upon Hemodynamics in Distal Vascular Graft Anastomoses: A Numerical Model Study

1994 ◽  
Vol 116 (3) ◽  
pp. 331-336 ◽  
Author(s):  
Ding-Yu Fei ◽  
James D. Thomas ◽  
Stanley E. Rittgers
Keyword(s):  
Numerical Model ◽  
Stagnation Point ◽  
Arterial Wall ◽  
Artery Bypass ◽  
Three Dimensional ◽  
Separated Flow ◽  
Reynolds Numbers ◽  
In Vivo Studies ◽  
Stagnation Points

Flow in distal end-to-side anastomoses of iliofemoral artery bypass grafts was simulated using a steady flow, three-dimensional numerical model. With the proximal artery occluded, anastomotic angles were varied over 20, 30, 40, 45, 50, 60 and 70 deg while the inlet Reynolds numbers were 100 and 205. Fully developed flow in the graft became somewhat skewed toward the inner wall with increasing angle for both Reynolds numbers. Separated flow regions were seen along the inner arterial wall (toe region) for angles ≥ 60 deg at Re = 100 and for angles ≥ 45 deg at Re = 205 while a stagnation point existed along the outer arterial wall (floor region) for all cases which moved downstream relative to the toe of the anastomosis with decreasing angles. Normalized shear rates (NSR) along the arterial wall varied widely throughout the anastomotic region with negative values seen in the separation zones and upstream of the stagnation points which increased in magnitude with angle. The NSR increased with distance downstream of the stagnation point and with magnitudes which increased with the angle. Compared with observations from chronic in vivo studies, these results appear to support the hypothesis of greater intimal hyperplasia occurring in regions of low fluid shear.

scholarly journals Repositioning FDA Drugs as Potential Cruzain Inhibitors from Trypanosoma cruzi: Virtual Screening, In Vitro and In Vivo Studies

Molecules ◽  
2017 ◽  
Vol 22 (6) ◽  
pp. 1015 ◽  
Author(s):  
Isidro Palos ◽  
Edgar E. Lara-Ramirez ◽  
Julio Cesar Lopez-Cedillo ◽  
Carlos Garcia-Perez ◽  
Muhammad Kashif ◽  
...  
Keyword(s):  
Virtual Screening ◽  
Trypanosoma Cruzi ◽  
In Vivo Studies ◽  
Screening In Vitro ◽  
Cruzain Inhibitors

Effects of NMDA receptor antagonists on visceromotor reflexes and on intestinal motility, in vivo

2007 ◽  
Vol 19 (7) ◽  
pp. 617-624 ◽  
Author(s):  
a. d. shafton ◽  
g. bogeski ◽  
p. d. kitchener ◽  
g. j. sanger ◽  
j. b. furness ◽  
...  
Keyword(s):  
Nmda Receptor ◽  
Intestinal Motility ◽  
Nmda Receptor Antagonists ◽  
Receptor Antagonists
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