scholarly journals Identification of APOE4 modulators, targeted therapeutic candidates in Coronary Artery Disease, using Molecular Docking studies

2021 ◽  
Author(s):  
Lima Hazarika ◽  
Supriyo Sen ◽  
Akshaykumar Zawar ◽  
Jitesh Doshi
Keyword(s):  
Coronary Artery Disease ◽  
Molecular Docking ◽  
Coronary Artery ◽  
Binding Affinity ◽  
Intramolecular Interaction ◽  
Docking Studies ◽  
Structural Basis ◽  
Molecular Docking Studies ◽  
Artery Disease ◽  
Drug Receptor

AbstractA significant genetic suspect for coronary artery disease is the pathological adaptation of apolipoprotein E4 (APOE4) through intramolecular interaction. With the prevailing evidences on APOE4 genotype and its prevalence in coronary artery disease, the present study has investigated the protein–ligand binding affinity and unveil the receptor binding abilities of different classes of ligands for APOE4 through molecular docking studies. Structural basis of APOE4 involvement in CAD suggests that the intramolecular domain interactions to be a suitable target for therapeutic intervention. Various classes of ligands including known drugs used in the treatment of CAD, fragment-based stabilizers and their similar structures and molecules with known bioactivity against APOE4 were screened for their binding affinity and further investigated for their interactions with APOE4. Computational studies show the benzyl amide derived structures to be useful candidates in modulation of APOE4. The dynamics of the binding analysis can be further achieved with an in-depth understanding of drug-receptor interactions performing molecular dynamic simulation studies.

A New Series Of 1,3-Dimethylxanthine Based Adenosine A2a Receptor Antagonists As A Non-Dopaminergic Treatment Of Parkinson’s Disease

2020 ◽  
Vol 17 ◽  
Author(s):  
Suman Rohilla ◽  
Ranju Bansal ◽  
Puneet Chauhan ◽  
Sonja Kachler ◽  
Karl-Norbert Klotz
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Molecular Docking ◽  
Binding Affinity ◽  
Docking Studies ◽  
Binding Modes ◽  
Molecular Docking Studies ◽  
In Silico Docking ◽  
Adenosine A2a Receptor Antagonists ◽  
The Impact

Background: Adenosine receptors (AR) have emerged as competent and innovative nondopaminergic targets for the development of potential drug candidates and thus constitute an effective and safer treatment approach for Parkinson’s disease (PD). Xanthine derivatives are considered as potential candidates for the treatment Parkinson’s disease due to their potent A2A AR antagonistic properties. Objective: The objectives of the work are to study the impact of substituting N7-position of 8-m/pchloropropoxyphenylxanthine structure on in vitro binding affinity of compounds with various AR subtypes, in vivo antiparkinsonian activity and binding modes of newly synthesized xanthines with A2A AR in molecular docking studies. Methods: Several new 7-substituted 8-m/p-chloropropoxyphenylxanthine analogues have been prepared. Adenosine receptor binding assays were performed to study the binding interactions with various subtypes and perphenazine induced rat catatonia model was used for antiparkinsonian activity. Molecular docking studies were performed using Schrödinger molecular modeling interface. Results: 8-para-substituted xanthine 9b bearing an N7-propyl substituent displayed the highest affinity towards A2A AR (Ki = 0.75 µM) with moderate selectivity versus other AR subtypes. 7-Propargyl analogue 9d produced significantly longlasting antiparkinsonian effects and also produced potent and selective binding affinity towards A2A AR. In silico docking studies further highlighted the crucial structural components required to develop xanthine derived potential A2A AR ligands as antiparkinsonian agents. Conclusion: A new series of 7-substituted 8-m/p-chloropropoxyphenylxanthines having good affinity for A2A AR and potent antiparkinsonian activity has been developed.

scholarly journals MOLECULAR DOCKING STUDIES ON THE THERAPEUTIC TARGETS OF ALZHEIMER'S DISEASE (AChE AND BChE) USING NATURAL BIOACTIVE ALKALOIDS

2016 ◽  
Vol 8 (12) ◽  
pp. 108
Author(s):  
Punabaka Jyothi ◽  
Kuna Yellamma
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Molecular Docking ◽  
Binding Affinity ◽  
Neurodegenerative Disorder ◽  
Biological Activities ◽  
Neuropsychiatric Symptoms ◽  
Docking Studies ◽  
Kcal Mole ◽  
Molecular Docking Studies

Objective: Alzheimer’s disease (AD), a progressive neurodegenerative disorder with many cognitive and neuropsychiatric symptoms, is biochemically characterized by a significant decrease in the brain neurotransmitter Acetylcholine (ACh).Methods: In the present insilico study, six plant bioactive compounds namely Harmol, Vasicine, Harmaline, Harmine, Harmane and Harmalol (from P. Nigellastrum Bunge) were analyzed for their inhibitory role on AChE (Acetylcholinesterase) and BChE (Butyrylcholinesterase) activity by applying the molecular docking studies. Other parameters viz. determination of molecular interaction-based binding affinity values, protein-ligand interactions, Lipinski rule of five, functional properties and biological activities for the above compounds were also calculated by employing the appropriate bioinformatics tools.Results: The results of docking analysis clearly showed that Harmalol has highest binding affinity with AChE (-8.6 kcal/mole) and BChE (-8.0 kcal/mole) but it does not qualified the enzyme inhibitory activity, since it was exerted, and also has least percentage activity on AD and neurodegenerative disease. Whereas, the Harmine has been second qualified binding affinity (-8.4 kcal/mol) and first in other parameters when compared with Harmalol.Conclusion: Based on docking results and other parameters conducted, we are concluding that Harmine is the best compound for further studies to treat AD.Keywords: Alzheimer's disease (AD), Acetylcholinesterase, Butyrylcholinesterase, Lead Molecules

scholarly journals SUSTAINED RELEASE TABLETS OF SORAFENIB-SILIBININ COMBINATIONS FOR THE TREATMENT OF HEPATOCELLULAR CARCINOMA

2018 ◽  
Vol 10 (5) ◽  
pp. 117
Author(s):  
Savita Mishra ◽  
Sandhya Hora ◽  
Vibha Shukla ◽  
Mukul Das ◽  
Harsha Kharkwal ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Drug Release ◽  
Sustained Release ◽  
Cell Line ◽  
Binding Affinity ◽  
Drug Combination ◽  
Docking Studies ◽  
Molecular Docking Studies ◽  
Weight Variation

Objective: The aim of this study was to develop polymer coated sustained release tablet using sorafenib and silibinin combination for the treatment of hepatocellular carcinoma.Methods: The qualitative analysis such as weight variation, friability, hardness, interaction studies, disintegration and in vitro release were performed to validate formulated tablets. We have maintained the acceptable official limits for weight variation, friability, hardness and disintegration time according to prescribed pharmacopoeial recommendation. In vitro drug release studies were performed using USP-II (paddle type) dissolution apparatus. The MTT assay was performed for assessment of Cell viability of drug combination for tablet formulation. Molecular docking studies have been performed to determine the combinatorial mode of action for the tablet formulation.Results: Friability and weight variation were less than 1% for each formulation, which were within range of prescribed pharmacopoeial recommendation. The hardness of 20 tablets showed 5-6.5Kg/cm2 for all formulations 5-6.5Kg/cm2. The optimized formulation resulted in 98% drug release after 28 h. The present study reports the synergistic effects of drug combination to inhibit cell growth in HepG2 cell line. Molecular docking studies showed that sorafenib has high binding affinity for B-Raf vascular endothelial growth factor receptor β and protein kinase B. Silibinin showed binding affinity with MAP kinase-11, protein phosphatase 2 A and tankyrase.Conclusion: The present study reports for the first time a novel formulation for sustained release and reduced toxicity of sorafenib with enhanced inhibitory effect of the drug combination on cancerous hepatic cell line as well collaborative mechanism of action for the formulation.

scholarly journals Estrogenic Effect of Scoparia dulcis (Linn) Extract in Mice Uterus and In Silico Molecular Docking Studies of Certain Compounds with Human Estrogen Receptors

2020 ◽  
Author(s):  
Khamhee Wangsa ◽  
Indira Sarma ◽  
Purbajyoti Saikia ◽  
Dhanabalan Ananthakrishnan ◽  
Hirendra Nath Sarma ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Estrogen Receptors ◽  
Binding Affinity ◽  
In Silico ◽  
Md Simulations ◽  
Docking Studies ◽  
Female Reproduction ◽  
Molecular Docking Studies ◽  
Scoparia Dulcis ◽  
In Silico Molecular Docking

Background: Scoparia dulcis Linn. is reported to be used by women of Assam and Arunachal Pradesh in northeast India for treating menstrual disorders. Scoparia dulcis contains compounds that bind with estrogen receptors (ERα and ERβ) evidenced by increased PCNA in endometrial epithelium. Methods: Crude extract was orally administered at the dose of 500 mg/kg body weight/day to the female mice (60–70 days old) in five different groups. Each group containing six females included: (I) cyclic control, (II) cyclic extract treated, (III) Ovariectomized (OVX)-vehicle treated (Control), (IV) OVX-E2 treated (V) OVX- extract treated. Extract was administered for eight days to the cyclic groups and three days to the OVX groups. PCNA was detected immunohistochemically in uterine tiss ues and signals were analyzed by Image J software (NIH, USA). Compounds were separated by GC-MS and identified using NIST. In silico molecular docking studies was performed with human estrogen receptors (ERα and ERβ). Molecular dynamics (MD) simulations of the best interacting compound was done using gromacs. Results: The results showed cell proliferation in the uterine endometrium evidenced by PCNA. Two phytocompounds, Octadecanoic acid and methyl stearate showed binding affinity with ERα and ERβ. Conclusion: Scoparia dulcis contains compounds having binding affinity with ERα and ERβ. The present study is the first report on compounds from Scoparia dulcis showing binding affinity with human estrogen receptors which may have biological effect on female reproduction.

In silico discovery of novel phytoconstituents of Amyris pinnata as mitotic spindle kinase inhibitor

2020 ◽  
Vol 12 ◽  
Author(s):  
Ghanshyam R. Parmar ◽  
Ashish P. Shah ◽  
Girish U. Sailor ◽  
Avinash Kumar Seth
Keyword(s):  
Molecular Docking ◽  
Binding Affinity ◽  
Mitotic Spindle ◽  
In Silico ◽  
Kinase Inhibitor ◽  
Pharmacokinetic Profile ◽  
Docking Studies ◽  
Chemotherapeutic Agents ◽  
Cancer Disease ◽  
Molecular Docking Studies

Background: Despite of many successes in discovery of numerous cancer chemotherapeutic agents from natural sources, some of the moieties were dropped because of its inefficiency or serious toxicity. Mitosis is an ordered series of fundamentally mechanical events in which identical copies of the genome are moved to two discrete locations within the dividing cell. The crucial role of the mitotic spindle in cell division has identified which is an important target in cancer chemotherapy. In the present study we are reporting molecular docking studies and in silico pharmacokinetic profile of selected phytoconstituents obtained from Amyris pinnata. Methods: Molecular docking studies of selected phytoconstituents were performed using iGEMDOCK. The crystal structure of protein was exported from protein data bank (PDB id: 4C4H). In silico pharmacokinetic profile of selected phytoconstituents were performed using SWISSADME server. Results: Compound AMNP6 showed higher binding affinity as compared to standard ligand. All the selected phytoconstituents has passed Lipinski rule of five and shown no violations. Conclusion: Good binding affinity and drug likeliness of the AMNP6 suggest that it can be further investigated and explored as mitotic spindle kinase inhibitor in cancer disease.

scholarly journals Evaluation of in vitro antioxidant, anticancer activities and molecular docking studies of Capparis zeylanica Linn. leaves

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Ruturaj A. Warake ◽  
Ravindra J. Jarag ◽  
Rakesh P. Dhavale ◽  
Rekha R. Jarag ◽  
Nikhil S. Lohar
Keyword(s):  
Molecular Docking ◽  
Binding Affinity ◽  
Leaf Extract ◽  
Docking Studies ◽  
Total Phenolic ◽  
Anticancer Activities ◽  
Her2 Protein ◽  
Molecular Docking Studies ◽  
Phenolic And Flavonoid

Abstract Background Capparis zeylanica Linn. leaf extract was subjected to phytochemical screening for the determination of antioxidant and anticancer activity on (MCF-7) human breast cancer cells. The phytoconstituents previously determined were subjected to molecular docking studies against human epidermal growth factor receptor 2 (HER2) protein as a target receptor to support antioxidant and anticancer activities. Results Powdered plant leaves were extracted by maceration method using ethyl acetate, chloroform, methanol, ethanol and distilled water. Preliminary phytochemical evaluation and total phenolic and flavonoid content of the extract were evaluated using biochemical tests. Total antioxidant capacity of the extract was evaluated using different assays. Anticancer potential of methanolic and ethanolic extracts was studied on human breast cancer cells. Molecular docking studies were performed to evaluate the binding interactions of phytoconstituents on HER2 protein using AutoDock Vina. Phytochemical evaluation confirmed the presence of saponins, flavonoids, tannins, phenols, carbohydrates and proteins. Ethanolic extract showed a maximum total phenolic and flavonoid content in support with antioxidant and anticancer activities. The ethanolic leaf extract showed 66.63% cell growth inhibition against MCF-7 cells. Molecular docking studies revealed the highest binding affinity (− 8.4 Kcal/mol) of α-amyrin followed by quercetin and β-carotene. Glucocapparin, syringic acid, vanillic acid and p-coumaric acid showed almost a similar binding affinity to the amino acid residues of HER2 protein as compared to 5-FU. Conclusion C. zeylanica leaf extract showed the presence of phenolic and flavonoid constituents responsible for antioxidant and in vitro anticancer activities. Molecular docking studies showed the binding affinity of phytoconstituents on targeted HER2 protein.

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