scholarly journals Evaluation of Inhibitory Activity In Silico of In-House Thiomorpholine Compounds between the ACE2 Receptor and S1 Subunit of SARS-CoV-2 Spike

Pathogens ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 1208
Author(s):  
Victor H. Vázquez-Valadez ◽  
Alejandro Hernández-Serda ◽  
Ma. Fernanda Jiménez-Cabiedes ◽  
Pablo Aguirre-Vidal ◽  
Ingrid González-Tapia ◽  
...  
Keyword(s):  
Inhibitory Activity ◽  
In Silico ◽  
De Novo ◽  
Computational Study ◽  
Antiviral Agents ◽  
Antihypertensive Agents ◽  
De Novo Design ◽  
Target Cells ◽  
Research Groups ◽  
International Scientific Community

At the end of 2019, the world was struck by the COVID-19 pandemic, which resulted in dire repercussions of unimaginable proportions. From the beginning, the international scientific community employed several strategies to tackle the spread of this disease. Most notably, these consisted of the development of a COVID-19 vaccine and the discovery of antiviral agents through the repositioning of already known drugs with methods such as de novo design. Previously, methylthiomorphic compounds, designed by our group as antihypertensive agents, have been shown to display an affinity with the ACE2 (angiotensin converting enzyme) receptor, a key mechanism required for SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) entry into target cells. Therefore, the objective of this work consists of evaluating, in silico, the inhibitory activity of these compounds between the ACE2 receptor and the S1 subunit of the SARS-CoV-2 spike protein. Supported by the advances of different research groups on the structure of the coronavirus spike and the interaction of the latter with its receptor, ACE2, we carried out a computational study that examined the effect of in-house designed compounds on the inhibition of said interaction. Our results indicate that the polyphenol LQM322 is one of the candidates that should be considered as a possible anti-COVID-19 agent.

2,4-Dichloro-5-[(N-aryl/alkyl)sulfamoyl]benzoic Acid Derivatives: In Vitro Antidiabetic Activity, Molecular Modeling and In silico ADMET Screening

2019 ◽  
Vol 15 (2) ◽  
pp. 186-195 ◽  
Author(s):  
Samridhi Thakral ◽  
Vikramjeet Singh
Keyword(s):  
Molecular Docking ◽  
Benzoic Acid ◽  
Inhibitory Activity ◽  
In Silico ◽  
Computational Study ◽  
Antidiabetic Activity ◽  
Standard Drug ◽  
Benzoic Acid Derivatives ◽  
In Silico Admet ◽  
Inhibitory Potential

Background: Postprandial hyperglycemia can be reduced by inhibiting major carbohydrate hydrolyzing enzymes, such as α-glucosidase and α-amylase which is an effective approach in both preventing and treating diabetes. Objective: The aim of this study was to synthesize a series of 2,4-dichloro-5-[(N-aryl/alkyl)sulfamoyl] benzoic acid derivatives and evaluate α-glucosidase and α-amylase inhibitory activity along with molecular docking and in silico ADMET property analysis. Method: Chlorosulfonation of 2,4-dichloro benzoic acid followed by reaction with corresponding anilines/amines yielded 2,4-dichloro-5-[(N-aryl/alkyl)sulfamoyl]benzoic acid derivatives. For evaluating their antidiabetic potential α-glucosidase and α-amylase inhibitory assays were carried out. In silico molecular docking studies of these compounds were performed with respect to these enzymes and a computational study was also carried out to predict the drug-likeness and ADMET properties of the title compounds. Results: Compound 3c (2,4-dichloro-5-[(2-nitrophenyl)sulfamoyl]benzoic acid) was found to be highly active having 3 fold inhibitory potential against α-amylase and 5 times inhibitory activity against α-glucosidase in comparison to standard drug acarbose. Conclusion: Most of the synthesized compounds were highly potent or equipotent to standard drug acarbose for inhibitory potential against α-glucosidase and α-amylase enzyme and hence this may indicate their antidiabetic activity. The docking study revealed that these compounds interact with active site of enzyme through hydrogen bonding and different pi interactions.

Towards the de novo design of DNA based catalytic sites using a combined NMR and in silico approach

2014 ◽  
Author(s):  
Dieter Buyst ◽  
V. Gheerardijn ◽  
J. Van Den Begin ◽  
A. Madder ◽  
J. C. Martins
Keyword(s):  
In Silico ◽  
De Novo ◽  
De Novo Design ◽  
Catalytic Sites

Structure-based de novo design and identification of D816V mutant-selective c-KIT inhibitors

2014 ◽  
Vol 12 (26) ◽  
pp. 4644-4655 ◽  
Author(s):  
Hwangseo Park ◽  
Soyoung Lee ◽  
Suhyun Lee ◽  
Sungwoo Hong
Keyword(s):  
Free Energy ◽  
Inhibitory Activity ◽  
High Selectivity ◽  
De Novo ◽  
Scoring Function ◽  
Solvation Free Energy ◽  
De Novo Design ◽  
Gain Of Function

New 7-azaindole-based c-KIT inhibitors with nanomolar inhibitory activity and high selectivity for the gain-of-function D816V mutant were identified through the structure-based de novo design using the scoring function improved by implementing an accurate solvation free energy.

scholarly journals de novo Design and in silico Optimization of Antibody-Like Binders Targeting Ebola Viral Antigen

2016 ◽  
Vol 110 (3) ◽  
pp. 537a
Author(s):  
Muyun Lihan ◽  
Boon Chong Goh ◽  
Tong Li ◽  
Costas D. Maranas ◽  
Klaus Shulten
Keyword(s):  
In Silico ◽  
Viral Antigen ◽  
De Novo ◽  
De Novo Design

Docking studies of tetra substituted pyrazolone derivatives as potential antiviral agents

2018 ◽  
Vol 5 (2) ◽  
pp. 5-8
Author(s):  
Jyothi Achuthanandhan ◽  
Baskar Lakshmanan
Keyword(s):  
Rna Polymerase ◽  
Inhibitory Activity ◽  
In Silico ◽  
Antiviral Agents ◽  
Docking Studies ◽  
Binding Modes ◽  
Binding Interaction ◽  
Rna Dependent Rna Polymerase ◽  
Adme Prediction ◽  
Pyrazolone Derivatives

In an attempt to find potential antiviral agents, a series of pyrazolones (PA1-PA6& PC1-PC6) were designed and evaluated for their  DENVNS5 (RNA-dependent RNA polymerase) inhibitory activity. Molecular docking studies of all the designed compounds into the binding site of DENVNS5 (PDB Code: 4C11) were performed to gain a comprehensive understanding into rational binding modes. These compounds were also screened for in silico drug-likeliness properties on the basis of the absorption, distribution, metabolism and excretion (ADME) prediction. Among all the synthesized compounds, analogue  PA6showed superior inhibitory activity against RNA dependent RNA polymerase. SAR  study indicated that the presence of an electron withdrawing substitution on pyrazolone derivatives significantly improves its binding interaction with the protein.Results of ADME prediction revealed that most of these compounds showed in silico drug-likeliness.

scholarly journals De-novo Drug Design, Molecular Docking and In-Silico Molecular Prediction of AChEI Analogues through CADD Approaches as Anti-Alzheimer’s Agents

2020 ◽  
Vol 16 (1) ◽  
pp. 54-72 ◽  
Author(s):  
Surabhi Pandey ◽  
B.K. Singh
Keyword(s):  
Molecular Docking ◽  
Drug Design ◽  
Inhibitory Activity ◽  
In Silico ◽  
Active Sites ◽  
De Novo ◽  
Docking Studies ◽  
Target Protein ◽  
Design And Development ◽  
Reference Drug

Background: There are over 44 million persons who suffer with Alzheimer’s disease (AD) worldwide, no existence of cure and only symptomatic treatments are available for it. The aim of this study is to evaluate the anti-Alzheimer potential of designed AChEI analogues using computer simulation docking studies. AChEIs are the most potential standards for treatment of AD, because they have proven efficacy. Among all AChEIs donepezil possesses lowest adverse effects, it can treat mildmoderate- severe AD and only once-daily dosing is required. Therefore, donepezil is recognized as a significant prototype for design and development of new drug molecule. Methods: In this study the Inhibitory potential of the design compounds on acetylcholinesterase enzyme has been evaluated. Docking studies has been performed which further analyzed by in-silico pharmacokinetic evaluation through pharmacopredicta after that Interaction modes with enzyme active sites were determined. Docking studies revealed that there is a strong interaction between the active sites of AChE enzyme and analyzed compounds. Results: As a result 26 compounds have been indicates better inhibitory activity on AChE enzyme and all the screening parameters have also been satisfied by all 26 compounds. From these 26 compounds, six compounds 17, 18, 24, 30, 36 and 56 are found to be the most potent inhibitors of this series by insilico study through INVENTUS v 1.1 software, having highest bio-affinities i.e. - 8.51, - 7.67, - 8.30, - 7.59, - 8.71 and -7.62 kcal/mol respectively, while the standard or reference drug donepezil had binding affinity of - 6.32 kcal/mol. Conclusion: Computer aided drug design approach has been playing an important role in the design and development of novel anti- AD drugs. With the help of structure based drug design some novel analogues of donepezil have been designed and the molecular docking studies with structure based ADME properties prediction studies is performed for prediction of AChE inhibitory activity. The binding mode of proposed compounds with target protein i.e. AChE has been evaluated and the resulting data from docking studies explains that all of the newly designed analogues had significantly high affinity towards target protein compared to donepezil as a reference ligand.

scholarly journals Target-templated de novo design of macrocyclic d-/l-peptides: discovery of drug-like inhibitors of PD-1

2021 ◽  
Vol 12 (14) ◽  
pp. 5164-5170
Author(s):  
Salvador Guardiola ◽  
Monica Varese ◽  
Xavier Roig ◽  
Macarena Sánchez-Navarro ◽  
Jesús García ◽  
...  
Keyword(s):  
Specific Surface ◽  
Protein Interactions ◽  
In Silico ◽  
Cyclic Peptides ◽  
De Novo ◽  
De Novo Design ◽  
Target Protein ◽  
Surface Patch ◽  
Protein Protein Interactions

In silico design of heterochiral cyclic peptides that bind to a specific surface patch on the target protein (PD-1, in this case) and disrupt protein–protein interactions.

scholarly journals De Novo Design of Protein Kinase Inhibitors by in Silico Identification of Hinge Region-Binding Fragments

2013 ◽  
Vol 8 (5) ◽  
pp. 1044-1052 ◽  
Author(s):  
Robert Urich ◽  
Grant Wishart ◽  
Michael Kiczun ◽  
André Richters ◽  
Naomi Tidten-Luksch ◽  
...  
Keyword(s):  
Protein Kinase ◽  
In Silico ◽  
Kinase Inhibitors ◽  
De Novo ◽  
De Novo Design ◽  
Protein Kinase Inhibitors ◽  
Hinge Region ◽  
In Silico Identification

In-vitro Cytotoxicity and Aromatase Inhibitory Activity of Flavonoids: Synthesis, Molecular Docking and In-silico ADME Prediction

2021 ◽  
Vol 21 ◽  
Author(s):  
Umang Shah ◽  
Samir Patel ◽  
Mehul Patel ◽  
Neeraj Jain ◽  
Nilesh Pandey ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Inhibitory Activity ◽  
In Silico ◽  
Computational Study ◽  
Cancer Cell Line ◽  
Inhibitory Effect ◽  
In Vitro Cytotoxicity ◽  
Spectroscopic Techniques ◽  
Reference Drug

Background: Many natural and synthetic flavonoids have been studied and documented by inhibiting aromatase enzymes for their anti-cancer activity against breast carcinoma. The aromatase enzyme is a possible target for the estrogen's positive breast cancer receptor. Objective: Hence, a series of flavonoids have been synthesized and assessed for their in vitro cytotoxicity and aromatase inhibitory activity. Methods: 39 flavonoids were synthesized and characterized by spectroscopic techniques, and their computational study was performed using the maestro version of the Schrodinger. In-silico ADME properties were checked by QikPro software. A total of 18 compounds were evaluated based on the docking score using cytotoxicity assay in human breast cancer cell line MCF-7. Results: Of the 18 compounds tested, 07 compounds, namely 2b, 8b, 14b, 15b, 19b, 24b, and 30b flavonoids were found to be more active with their IC50 values of 20.73 μM, 1.636 μM, 16.08 μM, 22.02 μM, 15.75 μM, 0.345 μM and 16.08 μM, respectively, compared with the reference drug letrozole. The in-vitro aromatase inhibitory activity of six compounds 2b, 8b, 14b, 19b, 24b, and 30b was conducted using a fluorogenic assay kit. The values of IC50 for compounds 2b and 24b were found to be 0.31 μM and 0.36 μM, respectively. Conclusion: Therefore, it was concluded that compounds 2b and 24b had a potent inhibitory effect of aromatase compared with letrozole with an IC50 value of 0.86 μM. At the same time, the other compounds 8b, 14b, 30b, and 19b were considered to have similar aromatase inhibitory activity. Hence, their essential aromatase inhibitory activities make them good lead candidates for developing potent inhibitors of aromatase.

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