Abstract
In the present work, molecular modeling studies have been reported on a series of diazine indole acetic acid derivatives to analyze the structure-activity relationship studies of CRTH2 using fragment (Topomer CoMFA and HQSAR) and field (CoMFA and CoMSIA) based QSAR methods. Twenty-six compounds were used as a training set to establish the model, and six compounds were used as a test set to validate the model. The generated models exhibited good statistical results such as correlation coefficient (r2) and the cross-validated correlation coefficient (q2). Topomer CoMFA analysis yielded the q2 of 0.610 and r2 of 0.981. HQSAR model generated using bond and connectivity as fragment distinction and 3-6 as fragment size has the q2 value of 0.707 and conventional r2 value of 0.892 with five components. CoMFA model was assessed by cross-validated q2 value of 0.543 and r2 value of 0.901 with steric and electrostatic fields. CoMSIA model generated using steric, hydrophobic and donor fields with q2 value of 0.550 and r2 value of 0.888 was found to be the optimal model among the various models generated. The contour maps were generated to analyze the important structural features that regulate their inhibitory potency. From the result of contour maps we have suggested the critical sites for chemical modification which will be useful in designing potent compounds with improved activity.
Keywords: CRTH2, Diazine indole acetic acid, Topomer CoMFA, HQSAR, CoMFA, CoMSIA.
Combinatorial Chemistry & High Throughput Screening
Title:Molecular Modeling Study on Diazine Indole Acetic Acid Derivatives for CRTH2 Inhibitory Activity
Volume: 19 Issue: 6
Author(s): Sathya Babu, Mottadi Rupa, Santhosh Kumar Nagarajan, Honglae Sohn and Thirumurthy Madhavan
Affiliation:
Keywords: CRTH2, Diazine indole acetic acid, Topomer CoMFA, HQSAR, CoMFA, CoMSIA.
Abstract: In the present work, molecular modeling studies have been reported on a series of diazine indole acetic acid derivatives to analyze the structure-activity relationship studies of CRTH2 using fragment (Topomer CoMFA and HQSAR) and field (CoMFA and CoMSIA) based QSAR methods. Twenty-six compounds were used as a training set to establish the model, and six compounds were used as a test set to validate the model. The generated models exhibited good statistical results such as correlation coefficient (r2) and the cross-validated correlation coefficient (q2). Topomer CoMFA analysis yielded the q2 of 0.610 and r2 of 0.981. HQSAR model generated using bond and connectivity as fragment distinction and 3-6 as fragment size has the q2 value of 0.707 and conventional r2 value of 0.892 with five components. CoMFA model was assessed by cross-validated q2 value of 0.543 and r2 value of 0.901 with steric and electrostatic fields. CoMSIA model generated using steric, hydrophobic and donor fields with q2 value of 0.550 and r2 value of 0.888 was found to be the optimal model among the various models generated. The contour maps were generated to analyze the important structural features that regulate their inhibitory potency. From the result of contour maps we have suggested the critical sites for chemical modification which will be useful in designing potent compounds with improved activity.
Export Options
About this article
Cite this article as:
Babu Sathya, Rupa Mottadi, Nagarajan Kumar Santhosh, Sohn Honglae and Madhavan Thirumurthy, Molecular Modeling Study on Diazine Indole Acetic Acid Derivatives for CRTH2 Inhibitory Activity, Combinatorial Chemistry & High Throughput Screening 2016; 19 (6) . https://dx.doi.org/10.2174/1386207319666160502123759
DOI https://dx.doi.org/10.2174/1386207319666160502123759 |
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
-
Cardiac Oxidative Stress and Inflammation are Similar in SAMP8 and SAMR1 Mice and Unaltered by Curcumin and Ginkgo biloba Extract Intake
Current Pharmaceutical Biotechnology Investigation of <i>ACE rs4646994, MTHFR rs1801133</i> and <i>VDR rs2228570</i> Genotypes in Jordanian Patients with Fibromyalgia Syndrome
Endocrine, Metabolic & Immune Disorders - Drug Targets Blood-Brain Barrier and Feeding: Regulatory Roles of Saturable Transport Systems for Ingestive Peptides
Current Pharmaceutical Design Progress in Multiple Sclerosis Genetics
Current Genomics CDC25 Phosphatase Inhibitors: An Update
Mini-Reviews in Medicinal Chemistry Biological Roles of the Eclectic Chromogranin-A-derived Peptide Catestatin
Current Medicinal Chemistry Calcium-related Neurotoxicity of Oxaliplatin: Understanding the Mechanisms to Drive Therapy
Current Medicinal Chemistry Gamma/Delta T Cell mRNA Levels Decrease at Mucosal Sites and Increase at Lymphoid Sites Following an Oral SIV Infection of Macaques
Current HIV Research Idiopathic Nephrotic Syndrome in Pediatrics: An Up-to-date
Current Pediatric Reviews Editorial [Hot Topic: New Developments in Drug and Vaccine Discoveries (Executive Editor: Aldar S. Bourinbaiar)]
Current Pharmaceutical Design Rational Design and Development of Colon-Specific Prodrugs
Current Topics in Medicinal Chemistry Microdialysis in Drug Discovery
Current Drug Discovery Technologies Cardiovascular Risk Factors in Chronic Inflammatory Rheumatic Diseases: Modern Assessment and Diagnosis
Current Vascular Pharmacology Identification of Potent Caspase-3 Inhibitors for Treatment of Multi- Neurodegenerative Diseases Using Pharmacophore Modeling and Docking Approaches
CNS & Neurological Disorders - Drug Targets [General Articles] Intracellular Thiol Concentration Modulating Inflammatory Response: Influence on the Regulation of Cell Functions Through Cysteine Prodrug Approach
Current Medicinal Chemistry Fast and Efficient Monitoring of Diclofenac Dissolution Profile by CE
Current Pharmaceutical Analysis Chlorogenic Acid: A Dietary Phenolic Acid with Promising Pharmacotherapeutic Potential
Current Medicinal Chemistry Protein Tyrosine Phosphatase SHP-2 as Drug Target
Mini-Reviews in Organic Chemistry Cytokine Release Syndrome in Pathogenesis and Treatment of COVID-19
Current Pharmaceutical Design Is there a Relationship between Endothelial Dysfunction of the Brachial Artery, Carotid Intima-Media Thickness and Soluble Receptors of Tumor Necrosis Factor-Alpha?
Vascular Disease Prevention (Discontinued)