Abstract
The present study deals with the development of an artificial neural network based quantitative structure activity relationship (QSAR) model for virtual screening of active compounds which contain androstenedione carbonskeleton or their similar skeleton at the core. An empirical data modeling (with fitted data mapping) has been performed on the basis of bioassay record for human breast cancer cell line MCF7. The whole experimental data set was considered as test set. Standard feed-forward back-propagation neural network technique was applied to build the model. Leave-One- Out (LOO) cross-validation was performed to evaluate the performance of the model. The mapped model became the basis for selection best mapped compounds followed by development of Pharmacophore specific secondary QSAR model. In the present study, two best mapped molecules ‘4beta-hydroxy Withanolide-E’ and ‘7, 8-Dehydrocalotropin’ were used for development of the secondary QSAR model. These secondary-QSAR models were resulted with R2 LOOCV value 0.9845 and 0.9666 respectively. Docking studies, in silico phamacokinetic and toxicity analysis was also done for selected compounds. The screened compounds CID_73621, CID_16757497, CID_301751, CID_390666 and CID_46830222 were found with promising binding affinity value with aromatase with reference to the co-crystallized control compound androstenedione. Due to excellent extent of variance coverage in ANN based QSAR map model, it can be used as a robust non-linear QSAR model for androstenedione carbon-skeleton containing molecules and the protocol can be used to derive secondary QSAR models for other compounds set.
Keywords: Androstenedione, ANN, MCF-7, QSAR, withanolide, Virtual Screening, Cytotoxic Activity, model, androstenedione carbonskeleton, non-linear QSAR model.
Combinatorial Chemistry & High Throughput Screening
Title:ANN-QSAR Model for Virtual Screening of Androstenedione C-Skeleton Containing Phytomolecules and Analogues for Cytotoxic Activity Against Human Breast Cancer Cell Line MCF-7
Volume: 16 Issue: 1
Author(s): Om Prakash, Feroz Khan, Rajender Singh Sangwan and Laxminarain Misra
Affiliation:
Keywords: Androstenedione, ANN, MCF-7, QSAR, withanolide, Virtual Screening, Cytotoxic Activity, model, androstenedione carbonskeleton, non-linear QSAR model.
Abstract: The present study deals with the development of an artificial neural network based quantitative structure activity relationship (QSAR) model for virtual screening of active compounds which contain androstenedione carbonskeleton or their similar skeleton at the core. An empirical data modeling (with fitted data mapping) has been performed on the basis of bioassay record for human breast cancer cell line MCF7. The whole experimental data set was considered as test set. Standard feed-forward back-propagation neural network technique was applied to build the model. Leave-One- Out (LOO) cross-validation was performed to evaluate the performance of the model. The mapped model became the basis for selection best mapped compounds followed by development of Pharmacophore specific secondary QSAR model. In the present study, two best mapped molecules ‘4beta-hydroxy Withanolide-E’ and ‘7, 8-Dehydrocalotropin’ were used for development of the secondary QSAR model. These secondary-QSAR models were resulted with R2 LOOCV value 0.9845 and 0.9666 respectively. Docking studies, in silico phamacokinetic and toxicity analysis was also done for selected compounds. The screened compounds CID_73621, CID_16757497, CID_301751, CID_390666 and CID_46830222 were found with promising binding affinity value with aromatase with reference to the co-crystallized control compound androstenedione. Due to excellent extent of variance coverage in ANN based QSAR map model, it can be used as a robust non-linear QSAR model for androstenedione carbon-skeleton containing molecules and the protocol can be used to derive secondary QSAR models for other compounds set.
Export Options
About this article
Cite this article as:
Prakash Om, Khan Feroz, Sangwan Singh Rajender and Misra Laxminarain, ANN-QSAR Model for Virtual Screening of Androstenedione C-Skeleton Containing Phytomolecules and Analogues for Cytotoxic Activity Against Human Breast Cancer Cell Line MCF-7, Combinatorial Chemistry & High Throughput Screening 2013; 16 (1) . https://dx.doi.org/10.2174/1386207311316010008
DOI https://dx.doi.org/10.2174/1386207311316010008 |
Print ISSN 1386-2073 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5402 |
Call for Papers in Thematic Issues
Artificial Intelligence Methods for Biomedical, Biochemical and Bioinformatics Problems
Recently, a large number of technologies based on artificial intelligence have been developed and applied to solve a diverse range of problems in the areas of biomedical, biochemical and bioinformatics problems. By utilizing powerful computing resources and massive amounts of data, methods based on artificial intelligence can significantly improve the ...read more
Eco-friendly Agents for Biological Control of Pathogenic Diseases
The discovery of an alternative biological approach to disease management includes work on medicinal products derived from natural sources as a starting point for the development of eco-friendly agents for these diseases and the injuries they cause, as well as reducing human contact with hazardous chemicals and their residues. We ...read more
Emerging trends in diseases mechanisms, noble drug targets and therapeutic strategies: focus on immunological and inflammatory disorders
Recently infectious and inflammatory diseases have been a key concern worldwide due to tremendous morbidity and mortality world Wide. Recent, nCOVID-9 pandemic is a good example for the emerging infectious disease outbreak. The world is facing many emerging and re-emerging diseases out breaks at present however, there is huge lack ...read more
Exploring Spectral Graph Theory in Combinatorial Chemistry
Scope of the Thematic Issue: Combinatorial chemistry involves the synthesis and analysis of a large number of diverse compounds simultaneously. Traditional methods rely on brute force experimentation, which can be time-consuming and resource-intensive. Spectral Graph Theory, a branch of mathematics dealing with the properties of graphs in relation to the ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Surgical Treatment in FIGO Stage I Cervical Cancer: Evolution of Concepts
Current Women`s Health Reviews Multi-Targeted Histone Deacetylase Inhibitors in Cancer Therapy
Current Medicinal Chemistry The ‘Arimidex’, Tamoxifen, Alone or in Combination (ATAC) Trial: A Step Forward in the Treatment of Early Breast Cancer
Reviews on Recent Clinical Trials Chemical Structure Characteristics and Bioactivity of Small Molecule FAK Inhibitors
Anti-Cancer Agents in Medicinal Chemistry ADAM Metalloproteinases as Potential Drug Targets
Current Medicinal Chemistry Neuropeptide Mimetics and Antagonists in the Treatment of Inflammatory Disease: Focus on VIP and PACAP
Current Topics in Medicinal Chemistry Pharmacokinetic Properties and In Silico ADME Modeling in Drug Discovery
Medicinal Chemistry Modular Protein Engineering in Emerging Cancer Therapies
Current Pharmaceutical Design Potential of Liposomes for Enhancement of Oral Drug Absorption
Current Drug Delivery Multi-targeting Andrographolide and its Natural Analogs as Potential Therapeutic Agents
Current Topics in Medicinal Chemistry Review on Epidermal Growth Factor Receptor (EGFR) Structure, Signaling Pathways, Interactions, and Recent Updates of EGFR Inhibitors
Current Topics in Medicinal Chemistry Oncologic Imaging End-Points for the Assessment of Therapy Response
Recent Patents on Anti-Cancer Drug Discovery A Tropical Lichen, Dirinaria consimilis Selectively Induces Apoptosis in MCF-7 Cells through the Regulation of p53 and Caspase-Cascade Pathway
Anti-Cancer Agents in Medicinal Chemistry ADAM Proteases: Protective Role in Alzheimers and Prion Diseases ?
Current Alzheimer Research Editorial (Thematic Issue: Challenging Organic Syntheses and Pharmacological Applications of Natural Products and their Derivatives – Part II)
Current Pharmaceutical Design Radiolabeled Small Molecule Inhibitors of VEGFR - Recent Advances
Current Pharmaceutical Design Incidental Extracardiac Findings on Coronary Computed Tomography Angiography: A Pictorial Review of Imaging Findings
Current Medical Imaging Hybrid PET Imaging in Neurologic Disease: PET/MRI Rather than PET/CT
Current Medical Imaging Editorial [Hot Topic: Targeting Cell Migration - The Next Generation Blockbusters (Guest Editors: Amanda E.I. Proudfoot, Marie Kosco-Vilbois and Zoe Johnson)]
Current Immunology Reviews (Discontinued) Drugging Cell Cycle Kinases in Cancer Therapy
Current Drug Targets