scholarly journals Molecular Docking Studies of Flavonoids from Andrographis paniculata as Potential Acetylcholinesterase, Butyrylcholinesterase and Monoamine Oxidase Inhibitors Towards the Treatment of Neurodegenerative Diseases

2020 ◽  
Vol 11 (3) ◽  
pp. 9871-9879
Keyword(s):  
Molecular Docking ◽  
Monoamine Oxidase ◽  
Neurodegenerative Diseases ◽  
Docking Studies ◽  
Monoamine Oxidase Inhibitors ◽  
Andrographis Paniculata ◽  
Lipinski’S Rule ◽  
Bioinformatic Tools ◽  
Pubchem Database ◽  
Lipinski’S Rule Of Five

Neurodegenerative diseases have been characterized by loss of neuron structures as well as their functions. This study was designed to assess molecular docking of flavonoids from Andrographis paniculata as potential acetylcholinesterase, butyrylcholinesterase, and monoamine oxidase inhibitors in the treatment of neurodegenerative diseases. Eight identified possible inhibitors of acetylcholinesterase, butyrylcholinesterase, and monoamine oxidase from Andrographis paniculata were retrieved from the PubChem database. The molecular docking, ADMET, and Lipinski’s rule of five were examined using different bioinformatic tools. It was shown that only rutin has the highest binding affinity (-12.6 kcal/mol) than the standard used. ADMET results demonstrated that all the eight compounds are druggable candidates except rutin. Also, only tangeritin has a blood-brain barrier (BBB) permeation potential. Hence, it can be deduced that all flavonoid compounds from Andrographis paniculata are orally druggable, which can make them useful in the treatment of neurodegenerative diseases better than donepezil.

scholarly journals Molecular docking, chemo-informatic properties, alpha-amylase, and lipase inhibition studies of benzodioxol derivatives

BMC Chemistry ◽  
2021 ◽  
Vol 15 (1) ◽  
Author(s):  
Mohammed Hawash ◽  
Nidal Jaradat ◽  
Suhaib Shekfeh ◽  
Murad Abualhasan ◽  
Ahmad M. Eid ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Docking Studies ◽  
Alpha Amylase ◽  
In Vivo Evaluation ◽  
Lipinski’S Rule ◽  
Drug Candidates ◽  
Lead Compounds ◽  
Lipase Enzyme ◽  
Lipinski’S Rule Of Five

AbstractCurrently, available therapies for diabetes could not achieve normal sugar values in a high percentage of treated patients. In this research project, a series of 17 benzodioxole derivatives were evaluated as antidiabetic agents; that belong to three different groups were evaluated against lipase and alpha-amylase (α-amylase) enzymes. The results showed that 14 compounds have potent inhibitory activities against α-amylase with IC50 values below 10 µg/ml. Among these compounds, 4f was the most potent compound with an IC50 value of 1.11 µg/ml compared to the anti-glycemic agent acarbose (IC50 6.47 µg/ml). On the contrary, these compounds showed weak or negligible activities against lipase enzyme. However, compound 6a showed the best inhibitory anti-lipase activity with IC50 44.1 µg/ml. Moreover, all the synthesized compounds were undergone Molinspiration calculation, and the result showed that all compounds obeyed Lipinski’s rule of five. Molecular docking studies were performed to illustrate the binding interactions between the benzodioxole derivatives and α-amylase enzyme pocket. Related to the obtained results it was clear that the carboxylic acid, benzodioxole ring, halogen or methoxy substituted aryl are important for the anti-amylase activities. The potent inhibitory results of some of the synthesized compounds suggest that these molecules should go further in vivo evaluation. It also suggests the benzodioxole derivatives as lead compounds for developing new drug candidates.

scholarly journals MOLECULAR DOCKING STUDY OF NEUROPROTECTIVEPLANT-DERIVED BIOMOLECULES IN PARKINSON’S DISEASE

2017 ◽  
Vol 9 (9) ◽  
pp. 149 ◽  
Author(s):  
Saurabh Kumar Jha ◽  
Pravir Kumar
Keyword(s):  
Molecular Docking ◽  
Docking Study ◽  
Docking Studies ◽  
Neuroprotective Activity ◽  
Therapeutic Window ◽  
Molecular Docking Study ◽  
Altered Expression ◽  
Lipinski’S Rule ◽  
Lipinski’S Rule Of Five ◽  
Free Energy Of Binding

Objective: The objective of this study was to explore the therapeutic role of biomolecules in targeting the altered expression of Parkin in PD pathogenesis.Methods: We employed various in silico tools such as drug-likeness parameters, namely, Lipinski filter analysis, Muscle tool for phylogenetic analysis, Castp Server for active site prediction, molecular docking studies using AutoDock 4.2.1 and LIGPLOT1.4.5 were carried out.Results: Our results show that neuroprotective activity of Quercetin to be most effective and can provide their possible clinical relevance in PD. Further, initial screenings of the molecules were done based on Lipinski’s rule of five. CastP server used to predict the ligand binding site suggests that this protein can be utilized as a potential drug target. Finally, we have found Quercetin to be most effective amongst four biomolecules in modulating Parkin based on minimum inhibition constant, Ki and highest negative free energy of binding with the maximum interacting surface area in a course of docking studies.Conclusion: This research could provide a potential therapeutic window for the treatment of PD.

Monoamine Oxidase Inhibitors: Ten Years of Docking Studies

2013 ◽  
Vol 12 (20) ◽  
pp. 2145-2162
Author(s):  
Giulio Ferino ◽  
Santiago Vilar ◽  
Maria J. Matos ◽  
Eugenio Uriarte ◽  
Enzo Cadoni
Keyword(s):  
Monoamine Oxidase ◽  
Docking Studies ◽  
Monoamine Oxidase Inhibitors

scholarly journals MOLECULAR DOCKING AND PHARMACOKINETIC PREDICTION OF HERBAL DERIVATIVES AS MALTASE-GLUCOAMYLASE INHIBITOR

2017 ◽  
Vol 10 (9) ◽  
pp. 392 ◽  
Author(s):  
Peter Juma Ochieng ◽  
Tony Sumaryada ◽  
Daniel Okun
Keyword(s):  
Molecular Docking ◽  
Surface Area ◽  
Docking Studies ◽  
Polar Surface Area ◽  
Autodock Vina ◽  
Standard Drug ◽  
Lipinski’S Rule ◽  
Structure Activity ◽  
Topological Polar Surface Area ◽  
High Binding Affinity

  Objective: To perform molecular docking and pharmacokinetic prediction of momordicoside F2, beta-sitosterol, and cis-N-feruloyltyramine herbal derivatives as maltase-glucoamylase (MGAM) inhibitors for the treatment of diabetes.Methods: The herbal derivatives and standard drug miglitol were docked differently onto MGAM receptor using AutoDock Vina software. In addition, Lipinski’s rule, drug-likeness, and absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties were analyzed using Molinspiration, ADMET structure–activity relationship, and prediction of activity spectra for substances online tools.Results: Docking studies reveal that momordicoside F2, beta-sitosterol, and cis-N-feruloyltyramine derivatives have high binding affinity to the MGAM receptor (−7.8, −6.8, and −6.5 Kcal/Mol, respectively) as compared to standard drug miglitol (−5.3 Kcal/Mol). In addition, all the herbal derivatives indicate good bioavailability (topological polar surface area <140 Ȧ and Nrot <10) without toxicity or mutagenic effects.Conclusion: The molecular docking and pharmacokinetic information of herbal derivatives obtained in this study can be utilized to develop novel MGAM inhibitors having antidiabetic potential with better pharmacokinetic and pharmacodynamics profile.

Structure-Based Docking Studies of GLUT4 Towards Exploring Selected Phytochemicals from Solanum xanthocarpum as a Therapeutic Target for the Treatment of Cancer

2019 ◽  
Vol 16 (4) ◽  
pp. 406-416 ◽  
Author(s):  
Babatunji Emmanuel Oyinloye ◽  
Tayo Alex Adekiya ◽  
Raphael Taiwo Aruleba ◽  
Oluwafemi Adeleke Ojo ◽  
Basiru Olaitan Ajiboye
Keyword(s):  
Glucose Transporter ◽  
Environmental Influence ◽  
Glucose Consumption ◽  
Docking Studies ◽  
The Body ◽  
Lipinski’S Rule ◽  
Pubchem Database ◽  
Potential Inhibitors ◽  
Cancerous Cells ◽  
Solanum Xanthocarpum

Background: In recent years, there has been an exponential increase in the global burden of cancer which has been associated with several factors including environmental influence, aging, diet, infectious agents, hormonal imbalance and chronic inflammation, among others. Cancerous cells utilize more glucose for its proliferation and survival than normal cells. Thus, the regulation of glucose consumption of cancerous cells through the inhibition of glucose transporter-4-protein (GLUT4) encoded by solute carrier family-2-member-4-gene (Slc2a4) by selected phytochemicals from Solanum xanthocarpum may serve as a new therapeutic candidate for the treatment of cancer. Methods: The seven identified potential inhibitors of GLUT4 from Solanum xanthocarpum were retrieved from PubChem database. Examination of their drug-likeness, toxicity prediction and molecular docking studies of these compounds with GLUT4 were carried out using online tools such as Molinspiration, PreADMET V.2.0 and Patchdock server. Results: The findings revealed that, five out of the seven compounds fulfil oral drugability of Lipinski’s rule of five (RO5) while two slightly meet the criteria of RO5. Conversely, five of the compounds are predicted to be mutagen while the remaining two are predicted to be safe for the body. Additionally, stigmasterol glucoside has higher binding-affinity (7590) with GLUT4 when compared to doxorubicin (6600) the control. Conclusion: These findings suggest that stigmasterol glucoside from Solanum xanthocarpum could be a promising therapeutic agent with better therapeutic efficacy than doxorubicin in the treatment of cancer via the inhibition of GLUT4.

scholarly journals AN IN SILICO STUDY OF NARINGENIN-MEDIATED NEUROPROTECTION IN PARKINSON’S DISEASE

2017 ◽  
Vol 10 (8) ◽  
pp. 171
Author(s):  
Saurabh Kumar Jha ◽  
Pravir Kumar
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Molecular Docking ◽  
In Silico ◽  
E3 Ligase ◽  
Docking Studies ◽  
Dimensional Structure ◽  
Molecular Docking Studies ◽  
Lipinski’S Rule ◽  
Ubiquitin E3 Ligase

  Objective: Naringenin is a dietary biomolecule with broad spectrum of activities which protects neurons from various neurotoxic insults and improves cognition and motor function in neurodegenerative diseases. DJ-1 has both, ubiquitin E3 ligase as well as chaperonic activity, and loss of ubiquitin E3 ligase activity of DJ-1 has been found to be associated with familial Parkinson’s disease (PD). Naringenin induced E3 ligase activity of DJ-1 which can have possible clinical relevance in PD.Methods: Various in silico parameters such as phylogenetic analysis, homology modeling, active site prediction, and molecular docking studies using AutoDock 4.2.1 and LIGPLOT1.4.5 were carried out.Results: Three-dimensional structure of DJ-1 was generated and Ramachandran plot was obtained for quality assessment. RAMPAGE displayed 99.5% of residues in the most favored regions. 0% residues in additionally allowed and 0.5% disallowed regions of DJ-1 protein. Further, initial screenings of the molecules were done based on Lipinski’s rule of five. CastP server used to predict the ligand binding site suggests that this protein can be utilized as a potential drug target. Finally, we have found naringenin to be most effective among four biomolecules in modulating DJ-1 based on minimum inhibition constant, Ki, and highest negative free energy of binding with maximum interacting surface area in the course of docking studies.Conclusion: Our study suggests that based on different in silico parameters and molecular docking studies, naringenin can provide a new avenue for PD therapeutics.

Development of fluorinated methoxylated chalcones as selective monoamine oxidase-B inhibitors: Synthesis, biochemistry and molecular docking studies

2015 ◽  
Vol 62 ◽  
pp. 22-29 ◽  
Author(s):  
Bijo Mathew ◽  
Githa Elizabeth Mathew ◽  
Gülberk Uçar ◽  
Ipek Baysal ◽  
Jerad Suresh ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Monoamine Oxidase ◽  
Docking Studies ◽  
Monoamine Oxidase B ◽  
Molecular Docking Studies

scholarly journals MOLECULAR DOCKING STUDIES FOR THE COMPARATIVE ANALYSIS OF DIFFERENT BIOMOLECULES TO TARGET HYPOXIA INDUCIBLE FACTOR-1α

2017 ◽  
Vol 9 (4) ◽  
pp. 83 ◽  
Author(s):  
Niraj Kumar Jha ◽  
Pravir Kumar
Keyword(s):  
Molecular Docking ◽  
In Silico ◽  
Hypoxia Inducible Factor ◽  
3D Structure ◽  
Amyloid Β ◽  
Docking Studies ◽  
Therapeutic Window ◽  
Hypoxic Exposure ◽  
Amyloid Β Protein ◽  
Lipinski’S Rule

Objective: Hypoxia plays a significant role in governing many vital signalling molecules in the central nervous system (CNS). Hypoxic exposure has also been depicted as a stimulus for oxidative stress, increase in lipid peroxidation, DNA damage, blood-brain dysfunction, impaired calcium (Ca2+) homoeostasis and agglomeration of oxidized biomolecules in neurons, which act as a novel signature in diverse neurodegenerative and oncogenic processes. On the contrary, the presence of abnormally impaired expression of HIF-1α under hypoxic insult could serve as an indication of the existence of tumors and neuronal dysfunction as well. For instance, under hypoxic stress, amyloid-β protein precursor (AβPP) cleavage is triggered due to the higher expression of HIF-1α and thus leads to synaptic loss. The objective of this research is to perform comparative studies of biomolecules in regulating HIF-1α activity based on in silico approaches that could establish a potential therapeutic window for the treatment of different abnormalities associated with impaired HIF-1α.Methods: We employed various in silico methods such as drug-likeness parameters namely Lipinski filter analysis, Muscle tool, SWISS-MODEL, active site prediction, Auto Dock 4.2.1 and LigPlot1.4.5for molecular docking studies.Results: 3D structure of HIF-1α was generated and Ramachandran plot obtained for quality assessment. RAMPAGE displayed 99.5% of residues in the most favoured regions. 0% residues in additionally allowed and 0.5% disallowed regions of the HIF-1α protein. Further, initial screenings of the molecules were done based on Lipinski’s rule of five. Cast P server used to predict the ligand binding site suggests that this protein can be utilised as a potential drug target. Finally, we have found Naringenin to be most effective amongst three biomolecules in modulating HIF-1α based on minimum inhibition constant, Ki and highest negative free energy of binding with the maximum interacting surface area during docking studies.Conclusion: The present study outlines the novel potential of Biomolecules in regulating HIF-1α activity for the treatment of different abnormalities associated with impaired HIF-1α.

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