Molecular Docking Studies of Dihydropyridazin-3(2H)-one Derivatives as Anticonvulsant Agents

2021 ◽  
Vol 6 (4) ◽  
pp. 270-283
Author(s):  
Sushil Prasad ◽  
Sukhbir Lal Khokra ◽  
Manish Devgun
Keyword(s):  
Molecular Docking ◽  
Binding Affinity ◽  
Rational Design ◽  
Docking Studies ◽  
Standard Drug ◽  
Branched Chain ◽  
Almost All ◽  
Derivatives Of ◽  
Affinity Score ◽  
Protein Active Site

Molecular docking is the identification of ligand’s correct binding geometry i.e. pose in the binding site and estimation of its binding affinity for rational design of drug molecule. The current study endeavored the high throughput in silico screening of 56 derivatives of dihydropyridazin-3(2H)-one docked with human cytosolic branched chain amino transferase using PyRx-virtual screening tool. Out of 56 compounds, almost all the test compounds showed very good binding affinity score. Gabapentin was used as standard drug which shows binding affinity of -6.2. On the basis of H-bond interactions, compounds 3, 9, 11, 25, 26, 31, 34, 39, 47, 48, 51, 54, 56 were found to be potent outcome for anticonvulsant activity. Compounds 11, 25, 39, 56 showed excellent H-bond interactions with protein active site, Among which compound 11 showed the outstanding interactions with acceptable bond length 2.34, 2.57, 2.62, 3.03 Å.

scholarly journals Molecular docking studies of dihydropyridazin-3(2H)-one derivatives as Antifungal, antibacterial and anti-helmintic agents

2021 ◽  
Vol 12 (1) ◽  
pp. 186-214
Author(s):  
Manish Devgun ◽  
Sushil Prasad ◽  
SukhbirLal Khokra ◽  
Rakesh Narang
Keyword(s):  
Molecular Docking ◽  
Binding Affinity ◽  
Rational Design ◽  
Antimicrobial Agents ◽  
Binding Free Energy ◽  
Docking Studies ◽  
Standard Drug ◽  
Almost All ◽  
Affinity Score ◽  
Protein Active Site

Molecular docking is the identification of ligand’s correct binding geometry i.e pose in the binding site and estimation of its binding affinity for the rational design of drug molecule. The current study endeavored the high throughput insilico screening of 24 compounds docked with their respective protein using PyRx-Virtual Screening Tool software. Out of 24 compounds, almost all test compounds showed a very good binding affinity score. Fluconazole was used as a standard drug in case of Antifungal, Ciprofloxacin in case of Antibacterial, and Albendazole in case of Antihelmintics. More negative is the binding free energy score, more favorable is the pose for binding to protein active site. Based on H-bond interactions of these 24 compounds, Compounds 3a5, 3c3, 3d5, 3d6 were found to be the similar outcome for antifungal activity as fluconazole, Compound3a1 for antibacterial, and Compounds 3b5, 3d6 for the antihelmintic agent. Furthermore, the affinity of any small ligand molecules can be considered as an extraordinary tool in the field of drug design and offer imminent in future examination to build up potent antimicrobial agents.

scholarly journals Computational Screening of Phytochemicals from Medicinal plants as COVID-19 Inhibitors

2020 ◽  
Author(s):  
Alisha Khandelwal ◽  
Tripti Sharma
Keyword(s):  
Molecular Docking ◽  
Medicinal Plants ◽  
Drug Development ◽  
Binding Affinity ◽  
Bioactive Compound ◽  
Docking Studies ◽  
Computational Screening ◽  
Natural Inhibitor ◽  
Almost All ◽  
High Binding Affinity

<p>In this research a dataset of plant based bioactive compound was developed. A total of 101 phytochemicals were selected, virtually designed and its binding affinity with ACE enzyme was studied by molecular docking. Human ACE related carboxypeptidase and complex (PDB ID: 1R42) and (PDB ID: 6CS2) were selected for molecular docking studies as corona virus binds to ACE2 to enter into the host cell. Docking score results revealed that almost all selected phytochemicals binds to the pocket of the human ACE protein with high binding affinity and the scores were compared with chloroquine and hydroxychloroquine. The drug likeliness and ADMET analysis of all the screened compounds were performed. Two potential compound 6-α-acetoxygedunin and echitamine exhibited optimum binding with both the receptor.These phytochemicals can serve as lead molecule for further optimization and drug development against COVID-19. Therefore, it is predicted that the insights in the present study could be regarded valuable towards development of natural inhibitor of this virus.</p>

scholarly journals in silico Anti-Cholinestarase Activity of Flavonoids: A Computational Approach

2019 ◽  
Vol 31 (12) ◽  
pp. 2859-2864
Author(s):  
Niraj Kumar Singh ◽  
Somdutt Mujwar ◽  
Debapriya Garabadu
Keyword(s):  
Molecular Docking ◽  
Binding Affinity ◽  
Docking Simulation ◽  
Docking Studies ◽  
Computational Approach ◽  
Molecular Docking Simulation ◽  
Flavonoid Compounds ◽  
Potent Inhibition ◽  
Potential Binding ◽  
Derivatives Of

In the present study, a computational approach has been designed to evaluate the potential anti-cholinesterase activity of derivatives of flavonoids. Molecular docking studies is performed for the 9 flavonoids against the human acetylcholine (ACh) enzyme to evaluate their binding affinity for having anti-alzheimer activity. All the 9 flavonoid compounds exhibited strong binding affinity that promises potent inhibition of human acetylcholine enzyme. Potential binding affinity of all the flavonoids against human acetylcholine enzyme confirms their possible mechanism of action by using AutoDock based molecular docking simulation technique. Thus, these flavonoid compounds could be presumed to be potential anti-cholinesterase drugs.

scholarly journals Computational Screening of Phytochemicals from Medicinal plants as COVID-19 Inhibitors

2020 ◽  
Author(s):  
Alisha Khandelwal ◽  
Tripti Sharma
Keyword(s):  
Molecular Docking ◽  
Medicinal Plants ◽  
Drug Development ◽  
Binding Affinity ◽  
Bioactive Compound ◽  
Docking Studies ◽  
Computational Screening ◽  
Natural Inhibitor ◽  
Almost All ◽  
High Binding Affinity

<p>In this research a dataset of plant based bioactive compound was developed. A total of 101 phytochemicals were selected, virtually designed and its binding affinity with ACE enzyme was studied by molecular docking. Human ACE related carboxypeptidase and complex (PDB ID: 1R42) and (PDB ID: 6CS2) were selected for molecular docking studies as corona virus binds to ACE2 to enter into the host cell. Docking score results revealed that almost all selected phytochemicals binds to the pocket of the human ACE protein with high binding affinity and the scores were compared with chloroquine and hydroxychloroquine. The drug likeliness and ADMET analysis of all the screened compounds were performed. Two potential compound 6-α-acetoxygedunin and echitamine exhibited optimum binding with both the receptor.These phytochemicals can serve as lead molecule for further optimization and drug development against COVID-19. Therefore, it is predicted that the insights in the present study could be regarded valuable towards development of natural inhibitor of this virus.</p>

scholarly journals One-Pot Synthesis of Novel Furochromone and Oxazocine Derivatives as Promising Antitumor Agents with Their Molecular Docking Studies

2020 ◽  
Vol 2020 ◽  
pp. 1-16
Author(s):  
Rita M. Borik
Keyword(s):  
Molecular Docking ◽  
Antitumor Agents ◽  
Docking Studies ◽  
One Pot ◽  
Simple Method ◽  
Standard Drug ◽  
Molecular Docking Studies ◽  
Benzoic Acid Derivatives ◽  
Derivatives Of ◽  
Good Agreement

One-pot efficient synthesis of novel chromone derivatives 4a–h and that of 5a–h were described in a simple method via four-component reaction between furochromone carbaldehyde, amine, isocyanate derivatives, and benzoic acid derivatives or nicotinic acid, respectively. Also, oxazocine derivatives 7a, b were prepared via reaction of visnagine carbaldehyde, ethyl acetoacetate and isocyanate derivatives 2a, b. The obtained derivatives of novel furochromone and oxazocine derivatives were evaluated as promising antitumor agents against panel of two human cell lines, hepatocellular carcinoma (HEPG2) and breast carcinoma (MCF7). The antitumor results suggested that furochromone derivatives 5a–h have activity against MCF7 in comparison with doxorubicin as the standard drug. Furthermore, the molecular docking studies of these novel derivatives of furochromone and oxazocine showed good agreement with the biological results when their binding pattern and affinity towards the active site of EGFR was investigate.

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, SYNTHESIS, MOLECULAR DOCKING, ADMET STUDIES AND BIOLOGICAL EVALUATION OF PYRAZOLINE INCORPORATED 1, 2, 3-TRIAZOLE BENZENE SULPHONAMIDES

2019 ◽  
pp. 6-15
Author(s):  
SRAVANTHI SILIVERI ◽  
NAGARAJU BASHABOINA ◽  
HARINADHA BABU VAMARAJU ◽  
Shiva Raj
Keyword(s):  
Molecular Docking ◽  
Cytotoxic Activity ◽  
Binding Affinity ◽  
Active Site ◽  
Docking Studies ◽  
Biological Evaluation ◽  
Standard Drug ◽  
Molecular Docking Studies ◽  
Anti Inflammatory ◽  
Potassium Oxonate

Objective: The main objective of this work was to design, synthesize and evaluate the novel pyrazoline incorporated 1,2,3-triazole benzene sulphonamides for cytotoxic and anti-gout activities also to perform Insilco molecular docking studies. Methods: Designed compounds were synthesized by condensation of different substituted chalcones (3a-i) with hydrazine hydrate and substituted phenylhydrazines. All the synthesized compounds were characterized on the basis of physical and spectral data. To predict the affinity and activity of the ligand molecule Libdock program was employed to generate different bioactive binding poses of designing molecules at the active site of protein Phosphatidylinositol 3-kinase (PI3Kα). Title compounds were evaluated for cytotoxic activity by using 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and anti-gout activity by potassium oxonate induced assay. Results: All the synthesized compounds showed characteristic peaks in FTIR, 1H, 13C NMR and MASS spectral analysis. In molecular docking studies, compound 3i has shown good binding affinity to the active site of PI3Kα with a docking score of 145.031 and 4 hydrogen bonding interactions with least hepatotoxicity and good bioavailability when compared with that of reference ligand KKR exhibited a Libdock score of 88.35. Remaining compounds also have a good binding affinity with a minimum of 2 bonding interactions and having better absorption, distribution, metabolism, elimination and toxicity (ADMET) profile. The same compound (3i) exhibited the highest cytotoxic activity with an IC50 value of 4.54µg/ml. Compound 4d was evaluated for anti-inflammatory activity and it has significantly ameliorated against potassium oxonate induced gout in mice when compared with that of standard drug allopurinol due to its anti-inflammatory property. Conclusion: We designed and synthesized a novel series of title compounds in quantitative yields and performed docking studies. New derivatives have a good binding affinity towards PI3Kα enzyme, good bioavailability, least hepatotoxicity and significant cytotoxic activity.

scholarly journals Molecular Docking of Some Monoazaphenothiazine Derivatives as Antimicrobial Agents

2020 ◽  
Vol 5 (2) ◽  
Keyword(s):  
Staphylococcus Aureus ◽  
Molecular Docking ◽  
Binding Affinity ◽  
Antimicrobial Activities ◽  
Diffusion Method ◽  
Standard Drug ◽  
Aniline Derivatives ◽  
In Silico Studies ◽  
Bacillus Spp ◽  
Derivatives Of

Purpose: This study was carried out to determine the antibacterial activities and molecular docking interactions of some aniline derivatives of monoazaphenothiazine earlier reported. Methods: The antimicrobial activities were determined by agar well diffusion method on Bacillus SPP, Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli. The 3D crystal structures of cryptogein complexed with cholesterol molecule, (PDB Code: 1LRI) and glucosamine 6-phosphate synthase (2VF5) complexed with glucosamine 6 phosphate (PDB Code: 2VF5) used for the present molecular docking studies were retrieved from the Protein Data Bank (PDB). Results: Compound 21 was most sensitive to Staphylococcus aureus with an MIC of 0.0625 mg/ml while compound 19 was most sensitive to Bacillus spp (MIC = 0.0625 mg/ml). Compound 22 gave the highest binding affinity with 2VF5 (11.51 kcal/ mol). Compounds 21 and 23 showed significant binding affinity for 1LRI comparable to the standard drug fluconazole. Conclusion: The aniline derivatives of monoazaphenothiazines were found to possess interesting antimicrobial activities. The in silico studies showed that the compounds had strong binding interactions with the drug receptors.

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 QSAR, molecular docking studies, ligand-based design and pharmacokinetic analysis on Maternal Embryonic Leucine Zipper Kinase (MELK) inhibitors as potential anti-triple-negative breast cancer (MDA-MB-231 cell line) drug compounds

2021 ◽  
Vol 45 (1) ◽  
Author(s):  
Hadiza Abdulrahman Lawal ◽  
Adamu Uzairu ◽  
Sani Uba
Keyword(s):  
Breast Cancer ◽  
Molecular Docking ◽  
Triple Negative Breast Cancer ◽  
Leucine Zipper ◽  
Triple Negative ◽  
Qsar Model ◽  
Docking Studies ◽  
Model Parameters ◽  
Standard Drug ◽  
Molecular Docking Studies

Abstract Background Cancer of the breast is known to be among the top spreading diseases on the globe. Triple-negative breast cancer is painstaking the most destructive type of mammary tumor because it spreads faster to other parts of the body, with high chances of early relapse and mortality. This research would aim at utilizing computational methods like quantitative structure–activity relationship (QSAR), performing molecular docking studies and again to further design new effective molecules using the QSAR model parameters and to analyze the pharmacokinetics “drug-likeliness” properties of the new compounds before they could proceed to pre-clinical trials. Results The QSAR model of the derivatives was highly robust as it also conforms to the least minimum requirement for QSAR model from the statistical assessments of (R2) = 0.6715, (R2adj) = 0.61920, (Q2) = 0.5460 and (R2pred) of 0.5304, and the model parameters (AATS6i and VR1_Dze) were used in designing new derivative compounds with higher potency. The molecular docking studies between the derivative compounds and Maternal Embryonic Leucine Zipper Kinase (MELK) protein target revealed that ligand 2, 9 and 17 had the highest binding affinities of − 9.3, − 9.3 and − 8.9 kcal/mol which was found to be higher than the standard drug adriamycin with − 7.8 kcal/mol. The pharmacokinetics analysis carried out on the newly designed compounds revealed that all the compounds passed the drug-likeness test and also the Lipinski rule of five. Conclusions The results obtained from the QSAR mathematical model of parthenolide derivatives were used in designing new derivatives compounds that were more effective and potent. The molecular docking result of parthenolide derivatives showed that compounds 2, 9 and 17 had higher docking scores than the standard drug adriamycin. The compounds would serve as the most promising inhibitors (MELK). Furthermore, the pharmacokinetics analysis carried out on the newly designed compounds revealed that all the compounds passed the drug-likeness test (ADME and other physicochemical properties) and they also adhered to the Lipinski rule of five. This gives a great breakthrough in medicine in finding the cure to triple-negative breast cancer (MBA-MD-231 cell line).

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