scholarly journals STUDY OF MAO-B INHIBITOR ANALOUGES FOR PARKINSON’S DISEASE THROUGH CADD APPROACHES

2018 ◽  
Vol 8 (5-s) ◽  
pp. 240-250
Author(s):  
Manish Bachhar ◽  
BK Singh
Keyword(s):  
Molecular Design ◽  
Neurodegenerative Disorder ◽  
Binding Mode ◽  
Docking Studies ◽  
Target Protein ◽  
Binding Affinities ◽  
Discovery Process ◽  
Drug Discovery Process ◽  
Mao B ◽  
Pharmacokinetic Properties

New derivatives are designed as target directed MAO-B Inhibitors for medical care of the patients for neurodegenerative disorder. Molecular design and estimated pharmacokinetic properties have been evaluated by using Inventus v 1.1 software. The binding mode of the proposed compounds with target protein i.e. 1S2Q was evaluated and the resulting data from docking studies explained that newly designed derivatives have high and better affinity towards target protein. Based on these properties, the binding affinities are used for speeding up drug discovery process by eliminating less potent compounds from synthesis. Keywords: MAO-B, Inventus, Target protein, Neurodegenerative, Docking.

Screening ,development of Transglutaminase-2 Inhibitors and its derivative as anti-lung cancer agent by insilico and invitro approach

2021 ◽  
Vol 17 ◽  
Author(s):  
Prachi P. Parvatikar ◽  
Sumangala Patil ◽  
Joy Hoskeri ◽  
Sandeep Swargam ◽  
Raghvendra Kulkarni ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Transglutaminase 2 ◽  
Docking Studies ◽  
Target Protein ◽  
Cellular Processes ◽  
Cytotoxicity Studies ◽  
Pharmacokinetic Properties ◽  
Cancer Agent ◽  
Inhibition Property ◽  
Cancer Inhibition

Aim: Screening and development of TG2 inhibitors as anti lung cancer agent. Background: Transglutaminase 2 (TG2) is multifunctional and ubiquitously expressed protein from transglutaminase family. It takes part in various cellular processes and plays an important role in the pathogenesis of autoimmune, neurodegerative and also cancer. Background: Transglutaminase 2 (TG2) is multifunctional and ubiquitously expressed protein from transglutaminase family. It takes part in various cellular processes and plays an important role in the pathogenesis of autoimmune, neurodegerative and also cancer. Objective : The of proposed study is to focused on screening of potent inhibitors of TG2 by in-silico method and synthesis its derivative as well as analysis of its activity by invitro approach. Material and Methods: Molecular docking studies have been carried on the different classes of TG2 inhibitors against the target protein. Nearly thirty TG2 inhibitors were selected from literature and docking was performed against transglutaminase 2. The computational ADME property screening was also carried out to check their pharmacokinetic properties. The compounds which exhibited positive ADME properties with good interaction with possessing least binding energy were further validated for their anti-lung cancer inhibition property against A549 cell lines by cytotoxicity studies. Results: The results of present study indicate that the docked complex formed by cystamine showed better binding affinity towards target protein so, this derivative of cystamine is formed using 2,5 dihydrobenzoic acid. Invitro results revealed that both molecule proved good cytotoxic agent against A549 lung cancer (875.10, 553.22 µg/ml) respectively. Further its activity should be validated on TG2 expressing lung cancer. Conclusion : Cystamine and its derivative can be act as potential therapeutic target for lung cancer but further its activity should be validated on TG2 expressing lung cancer.

scholarly journals Newly Synthesized Fluorinated Cinnamylpiperazines Possessing Low In Vitro MAO-B Binding

Molecules ◽  
2020 ◽  
Vol 25 (21) ◽  
pp. 4941
Author(s):  
Ivana I. Jevtić ◽  
Thu Hang Lai ◽  
Jelena Z. Penjišević ◽  
Sladjana Dukić-Stefanović ◽  
Deana B. Andrić ◽  
...  
Keyword(s):  
Binding Assay ◽  
Docking Studies ◽  
Emission Tomography ◽  
Binding Affinities ◽  
The Novel ◽  
Competitive Binding Assay ◽  
Mao B ◽  
Positron Emission ◽  
Further Development

Herein, we report on the synthesis and pharmacological evaluation of ten novel fluorinated cinnamylpiperazines as potential monoamine oxidase B (MAO-B) ligands. The designed derivatives consist of either cinnamyl or 2-fluorocinnamyl moieties connected to 2-fluoropyridylpiperazines. The three-step synthesis starting from commercially available piperazine afforded the final products in overall yields between 9% and 29%. An in vitro competitive binding assay using l-[3H]Deprenyl as radioligand was developed and the MAO-B binding affinities of the synthesized derivatives were assessed. Docking studies revealed that the compounds 8–17 were stabilized in both MAO-B entrance and substrate cavities, thus resembling the binding pose of l-Deprenyl. Although our results revealed that the novel fluorinated cinnamylpiperazines 8–17 do not possess sufficient MAO-B binding affinity to be eligible as positron emission tomography (PET) agents, the herein developed binding assay and the insights gained within our docking studies will certainly pave the way for further development of MAO-B ligands.

Recent Advancements in Docking Methodologies

Oncology ◽  
2017 ◽  
pp. 848-875
Author(s):  
Vijay Kumar Srivastav ◽  
Vineet Singh ◽  
Meena Tiwari
Keyword(s):  
Molecular Docking ◽  
Binding Free Energy ◽  
Binding Mode ◽  
Docking Studies ◽  
Protein Docking ◽  
Scoring Functions ◽  
Discovery Process ◽  
Ligand Complex ◽  
Small Molecule Databases ◽  
Homology Models

Nowadays molecular docking has become an important methodology in CADD (Computer-Aided Drug Design)-assisted drug discovery process. It is an important computational tool widely used to predict binding mode, binding affinity and binding free energy of a protein-ligand complex. The important factors responsible for accurate results in docking studies are correct binding site prediction, use of suitable small-molecule databases, consistent docking pose, high dock score with good MD (Molecular Dynamics), clarity whether the compound is an inhibitor or agonist, etc. However, still there are several limitations which make it difficult to obtain accurate results from docking studies. In this chapter, the main focus is on recent advancements in various aspects of molecular docking such as ligand sampling, protein flexibility, scoring functions, fragment docking, post-processing, docking into homology models and protein-protein docking.

scholarly journals Pyrazolobenzothiazine-based carbothioamides as new structural leads for the inhibition of monoamine oxidases: design, synthesis, in vitro bioevaluation and molecular docking studies

MedChemComm ◽  
2017 ◽  
Vol 8 (2) ◽  
pp. 452-464 ◽  
Author(s):  
Syed Mobasher Ali Abid ◽  
Sana Aslam ◽  
Sumera Zaib ◽  
Syeda Mahwish Bakht ◽  
Matloob Ahmad ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Active Site ◽  
Potent Inhibitor ◽  
Binding Mode ◽  
Docking Studies ◽  
Design Synthesis ◽  
Molecular Docking Studies ◽  
Monoamine Oxidases ◽  
Mao B

Binding mode of potent inhibitor (green) & cognate ligand (pink) in the active site of MAO-B.

Synthesis, anticancer activity, SAR and binding mode of interaction studies of substituted pentanoic acids: part II

2021 ◽  
Author(s):  
Sanchita Datta ◽  
Amit Kumar Halder ◽  
Nilanjan Adhikari ◽  
Sk Abdul Amin ◽  
Sanjib Das ◽  
...  
Keyword(s):  
Anticancer Agents ◽  
Leukemia Cell ◽  
Binding Mode ◽  
Docking Studies ◽  
Leukemia Cell Line ◽  
Pentanoic Acid ◽  
Dna Deformation ◽  
Pharmacokinetic Properties ◽  
New Compounds ◽  
Inhibiting Property

Aim: Our previous results suggest that phenyl/naphthylacetyl pentanoic acid derivatives may exhibit dual MMP-2 and HDAC8 inhibitory activities and show effective cytotoxic properties. Methodology: Here, 13 new compounds (C1–C13) were synthesized and characterized. Along with these new compounds, 16 previously reported phenyl/napthylacetyl pentanoic acid derivatives (C14–C29) were biologically evaluated. Results: Compounds C6 and C27 showed good cytotoxicity against leukemia cell line Jurkat E6.1. The mechanisms of cytotoxicity of these compounds were confirmed by DNA deformation assay and reactive oxygen species assay. MMP-2 and HDAC8 expression assays suggested the dual inhibiting property of these two compounds. These findings were supported by results of molecular docking studies. In silico pharmacokinetic properties showed compounds C6 and C27 have high gastrointestinal absorption. Conclusion: This study highlights the action of phenyl/naphthylacetyl pentanoic acid derivatives as anticancer agents.

scholarly journals Cytotoxicity and Antimycobacterial Properties of Pyrrolo[1,2-a]quinoline Derivatives: Molecular Target Identification and Molecular Docking Studies

Antibiotics ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 233 ◽  
Author(s):  
Katharigatta N. Venugopala ◽  
Vijayakumar Uppar ◽  
Sandeep Chandrashekharappa ◽  
Hassan H. Abdallah ◽  
Melendhran Pillay ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Target Identification ◽  
Multidrug Resistant ◽  
Docking Studies ◽  
Molecular Target ◽  
Culture Collection ◽  
Binding Affinities ◽  
Atcc Strain ◽  
Pharmacokinetic Properties ◽  
Resistant Strains

A series of ethyl 1-(substituted benzoyl)-5-methylpyrrolo[1,2-a]quinoline-3-carboxylates 4a–f and dimethyl 1-(substituted benzoyl)-5-methylpyrrolo[1,2-a]quinoline-2,3-dicarboxylates 4g–k have been synthesized and evaluated for their anti-tubercular (TB) activities against H37Rv (American Type Culture Collection (ATCC) strain 25177) and multidrug-resistant (MDR) strains of Mycobacterium tuberculosis by resazurin microplate assay (REMA). Molecular target identification for these compounds was also carried out by a computational approach. All test compounds exhibited anti-tuberculosis (TB) activity in the range of 8–128 µg/mL against H37Rv. The test compound dimethyl-1-(4-fluorobenzoyl)-5-methylpyrrolo[1,2-a]quinoline-2,3-dicarboxylate 4j emerged as the most promising anti-TB agent against H37Rv and multidrug-resistant strains of Mycobacterium tuberculosis at 8 and 16 µg/mL, respectively. In silico evaluation of pharmacokinetic properties indicated overall drug-likeness for most of the compounds. Docking studies were also carried out to investigate the binding affinities as well as interactions of these compounds with the target proteins.

scholarly journals GC–MS Analysis, Molecular Docking and Pharmacokinetic Properties of Phytocompounds from Solanum torvum Unripe Fruits and Its Effect on Breast Cancer Target Protein

2021 ◽  
Author(s):  
R. Saravanan ◽  
K. Raja ◽  
D. Shanthi
Keyword(s):  
Breast Cancer ◽  
Molecular Docking ◽  
Binding Affinity ◽  
Docking Studies ◽  
Target Protein ◽  
Solanum Torvum ◽  
Ms Analysis ◽  
Pharmacokinetic Properties ◽  
Synthetic Drug ◽  
Unripe Fruits

Abstract This study was designed to identify phytocompounds from the aqueous extract of Solanum torvum unripe fruits using GC–MS analysis against breast cancer. For this, the identified phytocompounds were subjected to perform molecular docking studies to find the effects on breast cancer target protein. Pharmacokinetic properties were also tested for the identified phytocompounds to evaluate the ADMET properties. Molecular docking studies were done using docking software PyRx, and pharmacokinetic properties of phytocompounds were evaluated using SwissADME. From the results, ten best compounds were identified from GC–MS analysis against breast cancer target protein. Of which, three compounds showed very good binding affinity with breast cancer target protein. They are ergost-25-ene-3,6-dione,5,12-dihydroxy-,(5.alpha.,12.beta.) (− 7.3 kcal/mol), aspidospermidin-17-ol,1-acetyl-16-methoxy (− 6.7 kcal/mol) and 2-(3,4-dichlorophenyl)-4-[[2-[1-methyl-2-pyrrolidinyl]ethyl amino]-6-[trichloromethyl]-s-triazine (− 6.7 kcal/mol). Further, docking study was performed for the synthetic drug doxorubicin to compare the efficiency of phytocompounds. The binding affinity of ergost-25-ene-3,6-dione,5,12-dihydroxy-,(5.alpha.,12.beta.) is higher than the synthetic drug doxorubicin (− 7.2 kcal/mol), and the binding affinity of other compounds is also very near to the drug. Hence, the present study concludes that the phytocompounds from the aqueous extract of Solanum torvum unripe fruits have the potential ability to treat breast cancer.

Recent Advancements in Docking Methodologies

2016 ◽  
pp. 267-294
Author(s):  
Vijay Kumar Srivastav ◽  
Vineet Singh ◽  
Meena Tiwari
Keyword(s):  
Molecular Docking ◽  
Binding Free Energy ◽  
Binding Mode ◽  
Docking Studies ◽  
Protein Docking ◽  
Scoring Functions ◽  
Discovery Process ◽  
Ligand Complex ◽  
Small Molecule Databases ◽  
Homology Models

Nowadays molecular docking has become an important methodology in CADD (Computer-Aided Drug Design)-assisted drug discovery process. It is an important computational tool widely used to predict binding mode, binding affinity and binding free energy of a protein-ligand complex. The important factors responsible for accurate results in docking studies are correct binding site prediction, use of suitable small-molecule databases, consistent docking pose, high dock score with good MD (Molecular Dynamics), clarity whether the compound is an inhibitor or agonist, etc. However, still there are several limitations which make it difficult to obtain accurate results from docking studies. In this chapter, the main focus is on recent advancements in various aspects of molecular docking such as ligand sampling, protein flexibility, scoring functions, fragment docking, post-processing, docking into homology models and protein-protein docking.

scholarly journals VIRTUAL SCREENING OF GINKGO BILOBA FOR THERAPEUTIC POTENTIALS AGAINST PARKINSON’S DISEASE

2016 ◽  
Vol 3 (1) ◽  
pp. 6-11
Author(s):  
Kavitha V ◽  
Jone Kirubavathy S ◽  
Sivaramkumar M.S ◽  
Velmurugan R
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Molecular Docking ◽  
Monoamine Oxidase ◽  
Ginkgo Biloba ◽  
Neurodegenerative Disorder ◽  
Docking Studies ◽  
Monoamine Oxidase B ◽  
Mao B ◽  
The Brain

Parkinson's disease (PD) is a neurodegenerative disorder that affects 2% of the population older than 60 years. Monoamine Oxidase B (MAO-B) inhibitors improve the symptoms of Parkinson's disease and can delay the progress. Inhibition of MAO-B, further prevent breakdown of dopamine in the brain and reducethe motor symptoms associated with PD. Ginkgo biloba has a number of therapeutic properties and contains phytonutrients that helps in improvement of neurological disorders. In present study, phytonutrients of Ginkgo biloba namely Myricetin, Quercetin, Isorhamnetin, Kaempferol, Ginkgolides A-C, and Ginkgolide J were selected for Molecular docking against Monoamine Oxidase-B enzyme. The Molecular Docking studies were performed using Autodock 4.2 and interaction between MAO-B and compounds were analyzed. The efficiency of the compound was screened based on the binding energy existing between the protein and inhibitor. The docking studies show that the phytochemicals of Ginkgo biloba against MAO-B were quite effective. The potential compound can be subjected to further clinical trials and can be an alternative in the future treatment of Parkinson’s disease.

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