Receptor-based QSAR study for a series of 3,3-disubstituted-5-aryl oxindoles and 6-aryl benzimidazol-2-ones derivatives as progesterone receptor inhibitors

Wang, J.H.; Hou, Qianqian; Tang, Ke; Cheng, Xian-Chao; Dong, Lin; Liu, Yanjie; Liu, C.B.

doi:10.1080/1062936x.2011.623324

Cited by 7 publications

(2 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Figure 3(a) (using Surflex-Dock). The docking results showed that four H-bonds are formed between the ligand (14) and protein (hDHODH). The carboxylic acid group in Compound 14 formed H-bonds with Arg136 and Gln47, which have already been found to be important residues for binding the ligand to the active site and also for providing inhibition.…”

Section: In Silico Admet Studiesmentioning

confidence: 99%

See 1 more Smart Citation

Development of docking-based 3D QSAR models for the design of substituted quinoline derivatives as human dihydroorotate dehydrogenase (hDHODH) inhibitors

Vyas

Ghate

2013

SAR and QSAR in Environmental Research

View full text Add to dashboard Cite

This study has investigated docking-based 3D quantitative structure-activity relationships (QSARs) for a range of quinoline carboxylic acid derivatives by comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA). A docking study has shown that most of the compounds formed H-bonds with Arg136 and Gln47, which have already been shown to be essential for the binding of ligands at the active site of the hydroorotate dehydrogenase adenovirus (hDHODH). Bioactive conformations of all the molecules obtained from the docking study were used for the 3D QSAR study. The best CoMFA and CoMSIA models were obtained for the training set and were found to be statistically significant, with cross-validated coefficients (q²) of 0.672 and 0.613, r² cv of 0.635 and 0.598 and coefficients of determination (r²) of 0.963 and 0.896, respectively. Both models were validated by a test set of 15 compounds, giving satisfactory predicted correlation coefficients (r² pred) of 0.824 and 0.793 for the CoMFA and CoMSIA models, respectively. From the docking-based 3D QSAR study we designed 34 novel quinoline-based compounds and performed structure-based virtual screening. Finally, in silico pharmacokinetics and toxicities were predicted for 24 of the best docked molecules. The study provides valuable information for the understanding of interactions between hDHODH and the novel compounds.

show abstract

Section: In Silico Admet Studiesmentioning

confidence: 99%

“…In CoMSIA similarity indices are calculated at regularly placed grid points for aligned molecules. CoMSIA calculates other molecular descriptors, such as hydrophobic fields, and H-bond donor and acceptor fields [13,14].…”

Section: Introductionmentioning

confidence: 99%

Development of docking-based 3D QSAR models for the design of substituted quinoline derivatives as human dihydroorotate dehydrogenase (hDHODH) inhibitors

Vyas

Ghate

2013

SAR and QSAR in Environmental Research

View full text Add to dashboard Cite

show abstract

3D-QSAR, molecular dynamics simulations, and molecular docking studies on pyridoaminotropanes and tetrahydroquinazoline as mTOR inhibitors

Chaube

Bhatt

2017

Mol Divers

View full text Add to dashboard Cite

Cancer is a second major disease after metabolic disorders where the number of cases of death is increasing gradually. Mammalian target of rapamycin (mTOR) is one of the most important targets for treatment of cancer, specifically for breast and lung cancer. In the present research work, Comparative Molecular Field Analysis (CoMFA) and Comparative Molecular Similarity Indices Analysis (CoMSIA) studies were performed on 50 compounds reported as mTOR inhibitors. Three different alignment methods were used, and among them, distill method was found to be the best method. In CoMFA, leave-one-out cross-validated coefficients [Formula: see text], conventional coefficient [Formula: see text], and predicted correlation coefficient [Formula: see text] values were found to be 0.664, 0.992, and 0.652, respectively. CoMSIA study was performed in 25 different combinations of features, such as steric, electrostatic, hydrogen bond donor, hydrogen bond acceptor, and hydrophobic. From this, a combination of steric, electrostatic, hydrophobic (SEH), and a combination of steric, electrostatic, hydrophobic, donor, and acceptor (SEHDA) were found as best combinations. In CoMSIA (SEHDA), [Formula: see text], [Formula: see text] and [Formula: see text] were found to be 0.646, 0.977, and 0.682, respectively, while in the case of CoMSIA (SEH), the values were 0.739, 0.976, and 0.779, respectively. Contour maps were generated and validated by molecular dynamics simulation-assisted molecular docking study. Highest active compound 19, moderate active compound 15, and lowest active compound 42 were docked on mTOR protein to validate the results of our molecular docking study. The result of the molecular docking study of highest active compound 19 is in line with the outcomes generated by contour maps. Based on the features obtained through this study, six novel mTOR inhibitors were designed and docked. This study could be useful for designing novel molecules with increased anticancer activity.

show abstract

Recent Advances in the Synthesis of Benzimidazol-2-ones via Rearrangements

Мамедов

Zhukova

2017

Progress in Heterocyclic Chemistry

View full text Add to dashboard Cite

Receptor-based QSAR study for a series of 3,3-disubstituted-5-aryl oxindoles and 6-aryl benzimidazol-2-ones derivatives as progesterone receptor inhibitors

Cited by 7 publications

References 52 publications

Development of docking-based 3D QSAR models for the design of substituted quinoline derivatives as human dihydroorotate dehydrogenase (hDHODH) inhibitors

Development of docking-based 3D QSAR models for the design of substituted quinoline derivatives as human dihydroorotate dehydrogenase (hDHODH) inhibitors

3D-QSAR, molecular dynamics simulations, and molecular docking studies on pyridoaminotropanes and tetrahydroquinazoline as mTOR inhibitors

Recent Advances in the Synthesis of Benzimidazol-2-ones via Rearrangements

Contact Info

Product

Resources

About