3D-QSAR and Molecular Docking Studies on Fused Pyrazoles as p38α Mitogen-Activated Protein Kinase Inhibitors

Lan, Ping; Huang, Zhijian; Sun, Jun-Rong; Chen, Weimin

doi:10.3390/ijms11093357

Cited by 24 publications

(8 citation statements)

References 21 publications

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“…With the 3D grid spacing of 2 Å in x, y and z axis, the Coulomb potentials and the Lennard-Jones were applied to calculate the energies of steric and electrostatic field 27 . The field values of CoMFA model were detected by a probe atom of a sp 3 hybridized carbon with the value cut off set at 30 kcal/mol 28 29 . For the CoMSIA method, two additional different fields of hydrophobic, hydrogen-bond acceptor were also calculated as an extension of steric and electrostatic fields 30 .…”

Section: Methodsmentioning

confidence: 99%

Prediction and evaluation of the lipase inhibitory activities of tea polyphenols with 3D-QSAR models

Chang

Deng

et al. 2016

Sci Rep

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The extraordinary hypolipidemic effects of polyphenolic compounds from tea have been confirmed in our previous study. To gain compounds with more potent activities, using the conformations of the most active compound revealed by molecular docking, a 3D-QSAR pancreatic lipase inhibitor model with good predictive ability was established and validated by CoMFA and CoMISA methods. With good statistical significance in CoMFA (r2cv = 0.622, r2 = 0.956, F = 261.463, SEE = 0.096) and CoMISA (r2cv = 0.631, r2 = 0.932, F = 75.408, SEE = 0.212) model, we summarized the structure-activity relationship between polyphenolic compounds and pancreatic lipase inhibitory activities and find the bulky substituents in R2, R4 and R5, hydrophilic substituents in R1 and electron withdrawing groups in R2 are the key factors to enhance the lipase inhibitory activities. Under the guidance of the 3D-QSAR results, (2R,3R,2′R,3′R)-desgalloyloolongtheanin-3,3′-O-digallate (DOTD), a potent lipase inhibitor with an IC50 of 0.08 μg/ml, was obtained from EGCG oxidative polymerization catalyzed by crude polyphenol oxidase. Furthermore, DOTD was found to inhibit lipid absorption in olive oil-loaded rats, which was related with inhibiting the activities of lipase in the intestinal mucosa and contents.

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Section: Methodsmentioning

confidence: 99%

Prediction and evaluation of the lipase inhibitory activities of tea polyphenols with 3D-QSAR models

Chang

Deng

et al. 2016

Sci Rep

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“…In this equation, SD is the sum of the squared deviations between the agonistic activities of the test set and the mean activity of the training molecules and PRESS is the sum of squared deviations between predicted and actual activity values for each molecule in the test set [ 13 , 24 , 25 , 26 ].…”

Section: Methodsmentioning

confidence: 99%

Molecular Modeling Studies on 11H-Dibenz[b,e]azepine and Dibenz[b,f][1,4]oxazepine Derivatives as Potent Agonists of the Human TRPA1 Receptor

Song

Wang

et al. 2010

Molecules

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A computational strategy based on comparative molecular fields analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) was performed on a series of the 11H-dibenz[b,e]azepine and dibenz[b,f][1,4]oxazepine derivatives as potent agonists of the human TRPA1 receptor. The CoMFA and CoMSIA models resulting from a 21 molecule training set gave r2cv values of 0.631 and 0.542 and r2 values of 0.986 and 0.981, respectively. The statistically significant models were validated by a test set of five compounds with predictive r2pred. values of 0.967 and 0.981 for CoMFA and CoMSIA, respectively. A systemic external validation was also performed on the established models. The information obtained from 3D counter maps could facilitate the design of more potent human TRPA1 receptor agonists.

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“…After obtaining the optimum number of components, a PLS analysis was performed with no validation and column filtering 2.0 to generate the highest correlation coefficient (r 2 ) [22].…”

Section: Partial Least Square Analysismentioning

confidence: 99%

3D-QSAR and Docking Studies on Pyrrolopyrimidine Derivatives as LIM-Kinase 2 Inhibitors

Sun¹,

Lan²,

Sun³

et al. 2011

LDDD

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The pyrrolopyrimidine derivatives have been regarded as a novel class of LIM-kinase 2 inhibitor. To explore the relationship between the structures of substituted pyrrolopyrimidine derivatives and their inhibitory activities against LIMK2, CoMFA and CoMSIA analyses, and molecular docking studies were performed on a dataset of forty-one compounds. The two 3D-QSAR models resulted from thirty-one molecules in the training set gave r 2 cv values of 0.635 and 0.660, r 2 values of 0.973 and 0.965, respectively. The predictive ability of CoMFA and CoMSIA, determined using a test set of ten compounds, gave predictive correlation coefficients of 0.971 and 0.964, respectively. 3D contour maps generated from CoMFA and CoMSIA along with the docking binding structures provided enough information about the structural requirements for better activity. The results can serve as a useful guideline to design novel LIMK2 inhibitors with better potencies.

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3D-QSAR and Molecular Docking Studies on Fused Pyrazoles as p38α Mitogen-Activated Protein Kinase Inhibitors

Cited by 24 publications

References 21 publications

Prediction and evaluation of the lipase inhibitory activities of tea polyphenols with 3D-QSAR models

Prediction and evaluation of the lipase inhibitory activities of tea polyphenols with 3D-QSAR models

Molecular Modeling Studies on 11H-Dibenz[b,e]azepine and Dibenz[b,f][1,4]oxazepine Derivatives as Potent Agonists of the Human TRPA1 Receptor

3D-QSAR and Docking Studies on Pyrrolopyrimidine Derivatives as LIM-Kinase 2 Inhibitors

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