Abstract
To optimize the physiochemical properties of 2-alkoxydihydrocinnamates as PPARα/γ dual agonist, a quantitative structure activity relationship, Hansch approach was made using combination of various thermodynamic, electronic and spatial descriptors. Several regression expressions are obtained using multiple linear regression analysis. The best QSAR model is further validated by leave-one-out cross validation method. Analyses of results from the present QSAR study suggest that for favorable dual PPARα/γ agonist activity electronic property of the substituents in hydrophobic tail phenyl ring plays a key role. The contribution of Hammett constant and dipole moment in the models deduced the importance of electron withdrawing substituents for dual activity. Additionally the study also indicates that bulky substituents in head acid moiety not confer selectivity towards the PPAR activity. Thus the QSAR study brings important structural insight to aid the design of dual PPARα/γ receptor agonist.
Keywords: QSAR, diabetes, hansch analysis, PPARα, PPARγ, hammett constant, dipole moment, heat of formation
Medicinal Chemistry
Title: Quantitative Structure Activity Analysis of 2-Alkoxydihydrocinnamates as PPARα /γ Dual Agonist
Volume: 4 Issue: 3
Author(s): P. Manoj Kumar, R. Hemalatha, S. C. Mahajan, C. Karthikeyan, N. S. Hari Narayana Moorthy and Piyush Trivedi
Affiliation:
Keywords: QSAR, diabetes, hansch analysis, PPARα, PPARγ, hammett constant, dipole moment, heat of formation
Abstract: To optimize the physiochemical properties of 2-alkoxydihydrocinnamates as PPARα/γ dual agonist, a quantitative structure activity relationship, Hansch approach was made using combination of various thermodynamic, electronic and spatial descriptors. Several regression expressions are obtained using multiple linear regression analysis. The best QSAR model is further validated by leave-one-out cross validation method. Analyses of results from the present QSAR study suggest that for favorable dual PPARα/γ agonist activity electronic property of the substituents in hydrophobic tail phenyl ring plays a key role. The contribution of Hammett constant and dipole moment in the models deduced the importance of electron withdrawing substituents for dual activity. Additionally the study also indicates that bulky substituents in head acid moiety not confer selectivity towards the PPAR activity. Thus the QSAR study brings important structural insight to aid the design of dual PPARα/γ receptor agonist.
Export Options
About this article
Cite this article as:
Kumar Manoj P., Hemalatha R., Mahajan C. S., Karthikeyan C., Hari Narayana Moorthy S. N. and Trivedi Piyush, Quantitative Structure Activity Analysis of 2-Alkoxydihydrocinnamates as PPARα /γ Dual Agonist, Medicinal Chemistry 2008; 4 (3) . https://dx.doi.org/10.2174/157340608784325188
DOI https://dx.doi.org/10.2174/157340608784325188 |
Print ISSN 1573-4064 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-6638 |
Call for Papers in Thematic Issues
Carbohydrates in Computational and Medicinal Chemistry
Carbohydrates are the most essential organic molecules and are involved in the maintenance of various physiological and metabolic processes in living organisms. Carbohydrate-based compounds have come to the attention of researchers because of their significant contributions to biological functions, such as cell development and cell proliferation, connections between several cells, ...read more
Recent Advances in the Medicinal Chemistry of Cancer
Scope of the Thematic Issue: Correlation between structure and function is one of the important aspects of the success of anti-cancer compounds associated with their structure-activity interactions, physiology, biochemical, molecular, and genetic processes. Overcoming these obstacles is key to obtaining further insights into developments in rational drug design, bioorganic chemistry, ...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
-
The Phosphodiesterase III Inhibitor Cilostazol Ameliorates Ethanolinduced Endothelial Dysfunction
Current Neurovascular Research Stem Cells and Cardiovascular Repair: A Role for Natural and Synthetic Molecules Harboring Differentiating and Paracrine Logics
Cardiovascular & Hematological Agents in Medicinal Chemistry The Role of PPARs in Obesity and other Insulin Resistance Associated Disorders
Current Medicinal Chemistry - Immunology, Endocrine & Metabolic Agents Molecular Probes for Malignant Melanoma Imaging
Current Pharmaceutical Biotechnology Diversified Synthetic Pathway of 1, 4-Dihydropyridines: A Class of Pharmacologically Important Molecules
Mini-Reviews in Medicinal Chemistry Have We Learnt all from IMPROVE-IT? Part I. Core Results and Subanalyses on the Effects of Ezetimibe Added to Statin Therapy Related to Age, Gender and Selected Chronic Diseases (Kidney Disease, Diabetes Mellitus and Non-Alcoholic Fatty Liver Disease)
Current Vascular Pharmacology Potential Therapeutic Relevance of Adenosine A2B and A2A Receptors in the Central Nervous System
CNS & Neurological Disorders - Drug Targets Naoxintong Protects against Atherosclerosis through Lipid-lowering and Inhibiting Maturation of Dendritic Cells in LDL Receptor Knockout Mice fed a High-fat Diet
Current Pharmaceutical Design Ambulatory Blood Pressure Monitoring in Type 2 Diabetes Mellitus: A Cross-sectional Study
Current Hypertension Reviews Association between the Polymorphisms of TLR4 and CD14 Genes and Alzheimers Disease
Current Pharmaceutical Design Potential Application of Biliverdin Reductase and its Fragments to Modulate insulin/IGF-1/MAPK/PI3-K Signaling Pathways in Therapeutic Settings
Current Drug Targets Simultaneous Monitoring of Febuxostat and Uric Acid in Human Serum Samples Using the Direct Square-Wave Voltammetric Method
Current Analytical Chemistry Synthetic Androgens as Designer Supplements
Current Neuropharmacology Social Cognition Deficit in Schizophrenia: Accounting for Pragmatic Deficits in Communication Abilities?
Current Psychiatry Reviews Driving Neural Stem Cells Towards a Desired Phenotype
Current Stem Cell Research & Therapy Thromboprophylaxis in Medical Patients: An Update
Vascular Disease Prevention (Discontinued) The Effects of Melatonin on the Oxidative Stress and Duration of Atrial Fibrillation after Coronary Artery Bypass Graft Surgery: A Randomized Controlled Trial
Endocrine, Metabolic & Immune Disorders - Drug Targets Myocardial Perfusion SPECT Imaging in Patients after Percutaneous Coronary Intervention
Current Cardiology Reviews Subject Index To Volume 1
Recent Patents on Anti-Cancer Drug Discovery Selected PET Radioligands for Ion Channel Linked Neuroreceptor Imaging: Focus on GABA, NMDA and nACh Receptors
Current Topics in Medicinal Chemistry