Use of Quantitative Structure–Activity Relationship (QSAR) and ADMET prediction studies as screening methods for design of benzyl urea derivatives for anti-cancer activity

Lokwani, Deepak K.; Bhandari, Shashikant V.; Pujari, Radha; Shastri, Padma; Shelke, Ganesh Vilas; Pawar, Vidya

doi:10.3109/14756366.2010.506437

Cited by 11 publications

(11 citation statements)

References 30 publications

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“…If the residual values obtained by the subtraction of the predicted activities from the biological activities are toward zero, the model is said to have a good predictive ability. The plots of observed versus predicted activities of both training and test set molecules helped in the cross-validation of the kNN-QSAR model [14, 17]. …”

Section: Methodsmentioning

confidence: 99%

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QSAR and Molecular Docking Studies of Oxadiazole-Ligated Pyrrole Derivatives as Enoyl-ACP (CoA) Reductase Inhibitors

Asgaonkar¹

2014

Sci. Pharm.

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A quantitative structure-activity relationship model was developed on a series of compounds containing oxadiazole-ligated pyrrole pharmacophore to identify key structural fragments required for anti-tubercular activity. Two-dimensional (2D) and three-dimensional (3D) QSAR studies were performed using multiple linear regression (MLR) analysis and k-nearest neighbour molecular field analysis (kNN-MFA), respectively. The developed QSAR models were found to be statistically significant with respect to training, cross-validation, and external validation. New chemical entities (NCEs) were designed based on the results of the 2D- and 3D-QSAR. NCEs were subjected to Lipinski’s screen to ensure the drug-like pharmacokinetic profile of the designed compounds in order to improve their bioavailability. Also, the binding ability of the NCEs with enoyl-ACP (CoA) reductase was assessed by docking.

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Section: Methodsmentioning

confidence: 99%

“…The standard error of estimate (SEE) was also considered before selecting a particular model [14, 17]. …”

Section: Methodsmentioning

confidence: 99%

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QSAR and Molecular Docking Studies of Oxadiazole-Ligated Pyrrole Derivatives as Enoyl-ACP (CoA) Reductase Inhibitors

Asgaonkar¹

2014

Sci. Pharm.

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“…XCSF is a piecewise linear function approximation system which approximates function values in the continuous space [1,11]. There are some differences between XCSF and XCS representation of conditions, classifier prediction mechanism, update process are some essential difference points between XCSF and XCS [12].…”

Section: Methodsmentioning

confidence: 99%

“…On the other hand, drug discovery is a costly and time consuming process. In this context, there is a great demand for predictive models to design new drugs with improved properties and diminished side effects [1]. Furthermore, there is also a demand for new methods that replace and reduce the use of laboratory animals [2].…”

Section: Introductionmentioning

confidence: 99%

An efficient piecewise linear model for predicting activity of caspase-3 inhibitors

et al. 2012

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Background and purpose of the studyMultimodal distribution of descriptors makes it more difficult to fit a single global model to model the entire data set in quantitative structure activity relationship (QSAR) studies.MethodsThe linear (Multiple linear regression; MLR), non-linear (Artificial neural network; ANN), and an approach based on “Extended Classifier System in Function approximation” (XCSF) were applied herein to model the biological activity of 658 caspase-3 inhibitors.ResultsVarious kinds of molecular descriptors were calculated to represent the molecular structures of the compounds. The original data set was partitioned into the training and test sets by the K-means classification method. Prediction error on the test data set indicated that the XCSF as a local model estimates caspase-3 inhibition activity, better than the global models such as MLR and ANN. The atom-centered fragment type CR2X2, electronegativity, polarizability, and atomic radius and also the lipophilicity of the molecule, were the main independent factors contributing to the caspase-3 inhibition activity.ConclusionsThe results of this study may be exploited for further design of novel caspase-3 inhibitors.

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Biosynthesis, total synthesis, structural modifications, bioactivity, and mechanism of action of the quinone‐methide triterpenoid celastrol

Lü

Liu

Zhou

et al. 2020

Medicinal Research Reviews

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Celastrol, a quinone‐methide triterpenoid, was extracted from Tripterygium wilfordii Hook. F. in 1936 for the first time. Almost 70 years later, it is considered one of the molecules most likely to be developed into modern drugs, as it exhibits notable bioactivity, including anticancer and anti‐inflammatory activity, and exerts antiobesity effects. In addition, the molecular mechanisms underlying its bioactivity are being widely studied, which offers new avenues for its development as a pharmaceutical reagent. Owing to its potential therapeutic effects and unique chemical structure, celastrol has attracted considerable interest in the fields of organic, biosynthesis, and medicinal chemistry. As several steps in the biosynthesis of celastrol have been revealed, the mechanisms of key enzymes catalyzing the formation and postmodifications of the celastrol scaffold have been gradually elucidated, which lays a good foundation for the future heterogeneous biosynthesis of celastrol. Chemical synthesis is also an effective approach to obtain celastrol. The total synthesis of celastrol was realized for the first time in 2015, which established a new strategy to obtain celastroid natural products. However, owing to the toxic effects and suboptimal pharmacological properties of celastrol, its clinical applications remain limited. To search for drug‐like derivatives, several structurally modified compounds were synthesized and tested. This review focuses primarily on the latest research progress in the biosynthesis, total synthesis, structural modifications, bioactivity, and mechanism of action of celastrol. We anticipate that this paper will facilitate a more comprehensive understanding of this promising compound and provide constructive references for future research in this field.

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Use of Quantitative Structure–Activity Relationship (QSAR) and ADMET prediction studies as screening methods for design of benzyl urea derivatives for anti-cancer activity

Cited by 11 publications

References 30 publications

QSAR and Molecular Docking Studies of Oxadiazole-Ligated Pyrrole Derivatives as Enoyl-ACP (CoA) Reductase Inhibitors

QSAR and Molecular Docking Studies of Oxadiazole-Ligated Pyrrole Derivatives as Enoyl-ACP (CoA) Reductase Inhibitors

An efficient piecewise linear model for predicting activity of caspase-3 inhibitors

Biosynthesis, total synthesis, structural modifications, bioactivity, and mechanism of action of the quinone‐methide triterpenoid celastrol

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