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 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 Natural xanthone compounds as promising drug candidates against COVID-19 - An integrated molecular docking and dynamics simulation study

2020 ◽  
Author(s):  
Shravan Kumar Gunda ◽  
Hima Kumari P ◽  
Gourav Choudhir ◽  
Anuj Kumar ◽  
P B. Kavi Kishor ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Antiviral Agents ◽  
Binding Energies ◽  
Dynamics Simulation ◽  
Lipinski’S Rule ◽  
Drug Candidates ◽  
Main Protease ◽  
Lipinski’S Rule Of Five ◽  
Dynamics Simulations ◽  
Potential Inhibitors

Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease2019 (COVID-19). SARS-CoV-2 is known for its high pathogenicity and transmission due to thepresence of polybasic cleavage sites. No specific drug is available for the treatment. To identifythe potential inhibitors, we have performed molecular docking against the SARS-CoV-2 mainprotease (6Y84) with fifteen important natural xanthone compounds. The docking results showedall the compounds exhibited good binding energies and interactions with the main protease. Thevalidation of representative docking complexes through molecular dynamics simulations showedthat xanthones binds with a higher binding affinity and lower free energy than the standardligand with Brasixanthone C and Brasixanthone B on 50 ns. Natural xanthone compounds havealso passed the Absorption, Distribution, Metabolism, and Excretion (ADME) property criteriaas well as Lipinski’s rule of five. The present integrated molecular docking and dynamicssimulations study unveil the use of xanthones as potential antiviral agents against SARS-CoV-2.

Can Antimalarial Phytochemicals be a Possible Cure for COVID-19? Molecular Docking Studies of Some Phytochemicals to SARS-CoV-2 3C-like Protease

2021 ◽  
Vol 21 ◽  
Author(s):  
Anamul Hasan ◽  
Khoshnur Jannat ◽  
Tohmina Afroze Bondhon ◽  
Rownak Jahan ◽  
Md Shahadat Hossan ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Docking Studies ◽  
Binding Energies ◽  
Binding Affinities ◽  
Drug Candidates ◽  
Lead Compounds ◽  
High Binding ◽  
Main Protease ◽  
Acridone Alkaloid ◽  
First Time

Objective: To evaluate the efficacy of reported anti-malarial phytochemicals as lead compounds for possible drug development against COVID-19. Methods: An in silico approach was used in this study to determine through molecular docking the binding affinities and site of binding of these phytochemicals to the 3C-like protease of COVID-19 which is considered as the main protease of the virus. Results: A number of anti-malarial phytochemicals like apigenin-7-O-glucoside, decurvisine, luteolin-7-O-glucoside, sargabolide J, and shizukaols A, B, F, and G showed predicted high binding energies with G values of -8.0 kcal/mol or higher. Shizukaols F and B demonstrated the best binding energies of -9.5 and -9.8, respectively. The acridone alkaloid 5-hydroxynoracronycine also gave a predicted high binding energy of -7.9 kcal/mol. Conclusion: This is for the first time that decursivine and several shizukaols were reported as potential anti-viral agents. These compounds merit further studies to determine whether they can be effective drug candidates against COVID-19.

scholarly journals Screening nucleotide and nucleoside analogues as potential inhibitors of SARS-CoV-2 RNA-dependent RNA polymerase by the molecular docking method for the treatment of COVID-19

2021 ◽  
Vol 63 (9) ◽  
pp. 14-21
Author(s):  
Thi Thu Hang Ta ◽  
◽  
Bao Kim Nguyen ◽  
Dang Huy Le ◽  
Thanh Tung Bui ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Rna Polymerase ◽  
Health Concern ◽  
Pharmacokinetic Parameters ◽  
Rna Dependent Rna Polymerase ◽  
Lipinski’S Rule ◽  
Docking Method ◽  
Lipinski’S Rule Of Five

The COVID-19 pandemic triggering acute respiratory syndrome is a major global health concern. The SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) enzyme regulating viral replication has been evaluated as a potential therapeutic target for inhibition of the infection of SARS-CoV-2. In this study, we evaluated the ability of RNA-dependent RNA polymerase drug inhibitors by using molecular docking in silico model. Lipinski’s rule of Five was used to evaluate drug - like properties of potential compound. Pharmacokinetic parameters of potential compounds were assessed using the pkCSM tool. Based on previous publications, we have collected 100 compounds. The results exhibited that 18 compounds have RdRp inhibitory activity stronger than the remdesivir as reference compounds. The Lipinski’s rule of Five showed that 17 among 18 compounds had proprietary drug-likenesss. Compounds including novuridine, didanosine, sofosbuvir, puromycin, defibrotite, gemcitabine, and nikkomycins are the most negative energies and have pharmacokinetic good absorption, not metabolised in the liver, excreted by the kidney and may have hepatotoxicity properties. Therefore, it is necessary to conduct the in vitro and in vivo assays to developthese compounds into drugs for COVID-19 treatment

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.

scholarly journals Computational Identification of Drug Lead Compounds for COVID-19 from Moringa Oleifera

2020 ◽  
Author(s):  
Dr. Divya Shaji
Keyword(s):  
Molecular Docking ◽  
Drug Targets ◽  
Moringa Oleifera ◽  
Docking Studies ◽  
World Health ◽  
Lipinski’S Rule ◽  
Lead Compounds ◽  
Global Pandemic ◽  
Drug Lead ◽  
Health Organization

<div>COVID-19 which is caused by the virus SARS-CoV-2, has now been declared a global pandemic by the World Health Organization. At present, no specific vaccines or drugs are available to treat COVID-19. Therefore, there is an urgent need for the identification of novel drug lead compounds</div><div>to treat COVID-19. The SARS-CoV-2 main protease (Mpro also known as 3CLpro) and RNA-dependent RNA polymerase (RdRp also known as nsp12) are the best-characterized drug targets among corona viruses. In order to discover the natural lead compounds for SARS-CoV-2, we</div><div>performed molecular docking with the compounds from <i>Moringa Oleifera</i> that target the Mpro and RdRp. The molecular docking studies were carried out using AutoDock Vina through PyRx. Drug-likeness property of the selected compounds was checked by applying the ‘Lipinski’s rule of five’ using Swiss ADME. The top four compounds with most favourable binding affinity were selected for each of the targets. The results indicated that the compounds kaempferol, pterygospermin, morphine and quercetin exhibited best binding energy towards Mpro and RdRp. This study suggests that these natural compounds could be promising candidates for further evaluation of COVID-19 prevention.</div>

scholarly journals Computational Identification of Drug Lead Compounds for COVID-19 from Moringa Oleifera

2020 ◽  
Author(s):  
Dr. Divya Shaji
Keyword(s):  
Molecular Docking ◽  
Drug Targets ◽  
Moringa Oleifera ◽  
Docking Studies ◽  
World Health ◽  
Lipinski’S Rule ◽  
Lead Compounds ◽  
Global Pandemic ◽  
Drug Lead ◽  
Health Organization

<div>COVID-19 which is caused by the virus SARS-CoV-2, has now been declared a global pandemic by the World Health Organization. At present, no specific vaccines or drugs are available to treat COVID-19. Therefore, there is an urgent need for the identification of novel drug lead compounds</div><div>to treat COVID-19. The SARS-CoV-2 main protease (Mpro also known as 3CLpro) and RNA-dependent RNA polymerase (RdRp also known as nsp12) are the best-characterized drug targets among corona viruses. In order to discover the natural lead compounds for SARS-CoV-2, we</div><div>performed molecular docking with the compounds from <i>Moringa Oleifera</i> that target the Mpro and RdRp. The molecular docking studies were carried out using AutoDock Vina through PyRx. Drug-likeness property of the selected compounds was checked by applying the ‘Lipinski’s rule of five’ using Swiss ADME. The top four compounds with most favourable binding affinity were selected for each of the targets. The results indicated that the compounds kaempferol, pterygospermin, morphine and quercetin exhibited best binding energy towards Mpro and RdRp. This study suggests that these natural compounds could be promising candidates for further evaluation of COVID-19 prevention.</div>

scholarly journals Synthesis, Characterization, Anti-Mycobacterial Evaluation and In-Silico Molecular Docking of Novel Isoxazole Clubbed Pyrimidine Derivatives

2021 ◽  
pp. 69-79
Author(s):  
Nagaraju Pappula ◽  
Ravichandra Sharabu
Keyword(s):  
Molecular Docking ◽  
Software Tool ◽  
Antitubercular Activity ◽  
Spectroscopic Studies ◽  
Docking Studies ◽  
Lipinski’S Rule ◽  
Mycobacterium Tuberculosis H37rv ◽  
Lead Compounds ◽  
H37rv Strain ◽  
In Silico Molecular Docking

In the present research, we tend to ready a series of novel pyrimidine-linked isoxazole derivatives (11-20). The molecular structure and the elemental composition of these compounds were confirmed by spectroscopic studies and elemental analysis. MABA (Microplate alamar Blue Assay) assay was employed for assessing the antitubercular activity against the Mycobacterium tuberculosis H37Rv strain. Among the ten synthesized compounds, 18 and 20 showed excellent anti-tubercular activity than the reference (MIC-3.125 µg/ml) at 0.78 µg/mL. The compounds were found to possess good binding affinity than a standard against thymidylate kinase enzyme (PDB-1MRS) as evidenced by the molecular docking studies. Additionally, the bioactivity was conducted by Mol-inspiration software tool and the drug-likeness property was evaluated on Lipinski's rule of five by SCFBio online software. The lead compounds identified through these studies could be useful for the furtherance of the drug discovery process in the area of antitubercular research.

scholarly journals Natural xanthone compounds as promising drug candidates against COVID-19 - An integrated molecular docking and dynamics simulation study

2021 ◽  
Author(s):  
Shravan Kumar Gunda ◽  
Hima Kumari P ◽  
Anuj Kumar ◽  
P B. Kavi Kishor ◽  
Anil Kumar S
Keyword(s):  
Molecular Docking ◽  
Antiviral Agents ◽  
Binding Energies ◽  
Dynamics Simulation ◽  
Lipinski’S Rule ◽  
Drug Candidates ◽  
Main Protease ◽  
Lipinski’S Rule Of Five ◽  
Dynamics Simulations ◽  
Potential Inhibitors

Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease2019 (COVID-19). SARS-CoV-2 is known for its high pathogenicity and transmission due to thepresence of polybasic cleavage sites. No specific drug is available for the treatment. To identifythe potential inhibitors, we have performed molecular docking against the SARS-CoV-2 mainprotease (6Y84) with fifteen important natural xanthone compounds. The docking results showedall the compounds exhibited good binding energies and interactions with the main protease. Thevalidation of representative docking complexes through molecular dynamics simulations showedthat xanthones binds with a higher binding affinity and lower free energy than the standardligand with Brasixanthone C and Brasixanthone B on 50 ns. Natural xanthone compounds havealso passed the Absorption, Distribution, Metabolism, and Excretion (ADME) property criteriaas well as Lipinski’s rule of five. The present integrated molecular docking and dynamicssimulations study unveil the use of xanthones as potential antiviral agents against SARS-CoV-2.

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