Furanone derivatives as new inhibitors of CDC7 kinase: development of structure activity relationship model using 3D QSAR, molecular docking, and in silico ADMET

2018 ◽  
Vol 29 (4) ◽  
pp. 1031-1043 ◽  
Author(s):  
Adnane Aouidate ◽  
Adib Ghaleb ◽  
Mounir Ghamali ◽  
Samir Chtita ◽  
Abdellah Ousaa ◽  
...  
Keyword(s):  
Molecular Docking ◽  
In Silico ◽  
3D Qsar ◽  
Structure Activity Relationship ◽  
Activity Relationship ◽  
Structure Activity ◽  
In Silico Admet ◽  
Relationship Model ◽  
Cdc7 Kinase

scholarly journals In Silico Exploration of Aryl Halides Analogues as CheckpointKinase 1 Inhibitors by Using 3D QSAR, Molecular Docking Study,and ADMET Screening

2019 ◽  
Vol 9 (1) ◽  
pp. 84-92 ◽  
Author(s):  
Adib Ghaleb ◽  
Adnane Aouidate ◽  
Mohammed Bouachrine ◽  
Tahar Lakhlifi ◽  
Abdelouhid Sbai
Keyword(s):  
Molecular Docking ◽  
Drug Design ◽  
In Silico ◽  
3D Qsar ◽  
Structure Activity Relationship ◽  
Aryl Halides ◽  
Activity Relationship ◽  
Computer Aided Drug Design ◽  
Structure Activity ◽  
Computer Aided

Purpose: In this review, a set of aryl halides analogs were identified as potent checkpoint kinase1 (Chk1) inhibitors through a series of computer-aided drug design processes, to develop modelswith good predictive ability, highlight the important interactions between the ligand and theChk1 receptor protein and determine properties of the new proposed drugs as Chk1 inhibitorsagents.Methods: Three-dimensional quantitative structure–activity relationship (3D-QSAR) modeling,molecular docking and absorption, distribution, metabolism, excretion and toxicity (ADMET)approaches are used to determine structure activity relationship and confirm the stableconformation on the receptor pocket.Results: The statistical analysis results of comparative -molecular field analysis (CoMFA) andcomparative molecular similarity indices analysis (CoMSIA) models that employed for a trainingset of 24 compounds gives reliable values of Q2 (0.70 and 0.94, respectively) and R2 (0.68 and0.96, respectively).Conclusion: Computer–aided drug design tools used to develop models that possess goodpredictive ability, and to determine the stability of the observed and predicted molecules in thereceptor pocket, also in silico of pharmacokinetic (ADMET) results shows good properties andbioavailability for these new proposed Chk1 inhibitors agents.

3D-QSAR Assisted Design of Novel 7-Deazapurine Derivatives as TNNI3K Kinase Inhibitors Using Molecular Docking and Molecular Dynamics Simulation

2020 ◽  
Vol 17 (2) ◽  
pp. 155-168
Author(s):  
Pavithra K. Balasubramanian ◽  
Anand Balupuri ◽  
Swapnil P. Bhujbal ◽  
Seung Joo Cho
Keyword(s):  
Molecular Dynamics ◽  
Molecular Docking ◽  
Molecular Dynamics Simulation ◽  
3D Qsar ◽  
Structure Activity Relationship ◽  
Dynamics Simulation ◽  
Activity Relationship ◽  
Dual Function ◽  
Contour Maps ◽  
Structure Activity

Background: Cardiac troponin I-interacting kinase (TNNI3K) is a cardiac-specific kinase that belongs to MAPKKK family. It is a dual-function kinase with tyrosine and serine/threonine kinase activity. Over-expression of TNNI3K results in various cardiovascular diseases such as cardiomyopathy, ischemia/reperfusion injury, heart failure, etc. Since, it is a cardiac-specific kinase and expressed only in heart tissue, it is an ideal molecular target to treat cardiac diseases. The main objective of the work is to study and understand the structure-activity relationship of the reported deazapurine derivatives and to use the 3D-QSAR and docking results to design potent and novel TNNI3K inhibitors of this series. Methods: In the present study, we have used molecular docking 3D QSAR, and molecular dynamics simulation to understand the structure-activity correlation of reported TNNI3K inhibitors and to design novel compounds of deazapurine derivatives with increased activity. Results: Both CoMFA (q2=0.669, NOC=5, r2=0.944) and CoMSIA (q2=0.783, NOC=5, r2=0.965) have resulted in satisfactory models. The models were validated using external test set, Leave-out- Five, bootstrapping, progressive scrambling, and rm2 metrics calculations. The validation procedures showed the developed models were robust and reliable. The docking results and the contour maps analysis helped in the better understanding of the structure-activity relationship. Conclusion: This is the first report on 3D-QSAR modeling studies of TNNI3K inhibitors. Both docking and MD results were consistent and showed good correlation with the previous experimental data. Based on the information obtained from contour maps, 31 novel TNNI3K inhibitors were designed. These designed compounds showed higher activity than the existing dataset compounds.

scholarly journals 3D-QSAR, ADMET and Molecular Docking Study of a Series of 2-Substituted 1H-Benzimidazole-4-Carboxamide Derivatives Inhibitors Against Enteroviruses

2021 ◽  
Vol 12 (6) ◽  
pp. 8128-8143
Keyword(s):  
Molecular Docking ◽  
Cross Validation ◽  
3D Qsar ◽  
Docking Study ◽  
Structure Activity Relationship ◽  
Activity Relationship ◽  
Coxsackievirus A16 ◽  
Molecular Docking Study ◽  
Structure Activity ◽  
Coxsackievirus B

A series of bioactive benzimidazoles were theoretically evaluated for their effect against enteroviruses, particularly coxsackievirus B and coxsackievirus A16. The structure-activity relationship allowed to deduce a very efficient model that can be used as a reference for the synthesis of compounds against this type of virus. The model used is essentially based on the RML and NN method, and its validation was carried out using cross-validation. The results obtained by molecular docking and ADMET of compound 9 as an inhibitor of enterovirus A16 give the proposal of the drug of this series.

In vitro α-Glucosidase Inhibition by Non-sugar based Triazoles of Dibenzoazepine, their Structure-Activity Relationship, and Molecular Docking

2017 ◽  
Vol 13 (7) ◽  
Author(s):  
Maria A. Khan ◽  
Kulsoom Javaid ◽  
Abdul Wadood ◽  
Alam Jamal ◽  
Farhana Batool ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Structure Activity Relationship ◽  
Activity Relationship ◽  
Structure Activity

Towards further Understanding the Structural Requirements of Combretastatin- like Chalcones as Inhibitors of Microtubule Polymerization

2020 ◽  
Vol 16 (2) ◽  
pp. 155-166
Author(s):  
Naveen Dhingra ◽  
Anand Kar ◽  
Rajesh Sharma
Keyword(s):  
Three Dimensional ◽  
3D Qsar ◽  
Docking Study ◽  
Structure Activity Relationship ◽  
Docking Studies ◽  
Activity Relationship ◽  
Structural Requirement ◽  
Ligand Interaction ◽  
Microtubule Polymerization ◽  
Structure Activity

Background: Microtubules are dynamic filamentous cytoskeletal structures which play several key roles in cell proliferation and trafficking. They are supposed to contribute in the development of important therapeutic targeting tumor cells. Chalcones are important group of natural compounds abundantly found in fruits & vegetables that are known to possess anticancer activity. We have used QSAR and docking studies to understand the structural requirement of chalcones for understanding the mechanism of microtubule polymerization inhibition. Methods: Three dimensional (3D) QSAR (CoMFA and CoMSIA), pharmacophore mapping and molecular docking studies were performed for the generation of structure activity relationship of combretastatin-like chalcones through statistical models and contour maps. Results: Structure activity relationship revealed that substitution of electrostatic, steric and donor groups may enhance the biological activity of compounds as inhibitors of microtubule polymerization. From the docking study, it was clear that compounds bind at the active site of tubulin protein. Conclusion: The given strategies of modelling could be an encouraging way for designing more potent compounds as well as for the elucidation of protein-ligand interaction.

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