Abstract
With a view to develop novel non-TZD anti-diabetic compounds, series of isoxazolidinediones were designed to target the PPAR-γ receptors. Docking studies were performed on co-crystallized protein structure of rosiglitazone with PPAR-γ receptor obtained from Protein Data Bank (2PRG). Interactions similar to that of rosiglitazone were observed for three molecules; 3a, 3b and 3c which were further synthesized and subjected to in vivo hypoglycemic, total cholesterol (CHL) and triglyceride (TG) evaluation. 14 days treatment revealed significant reduction in blood glucose levels but did not portray desirable results in terms of total CHL and TG lowering effect. The blood glucose reduction observed for 3a, 3b and 3c at 20 mg/kg/day was 53.96 %, 61.35%, 61.32% respectively as against 59.95% of the standard pioglitazone at 10mg/kg/day.
Keywords: 4-benzylidene-3, 5-isoxazolidinedione, docking, HFD- low STZ model, hypoglycemic activity , Knoevenagel condensation
Medicinal Chemistry
Title:Design, Synthesis and In-vivo Hypoglycemic Evaluation of Novel Non - TZD’S in a Type - 2 Diabetic Model
Volume: 9 Issue: 1
Author(s): Rupali Jadhav, Ranu Gupta-Rajoria, Tanushree Pal and Ramaa Chelakara Subramanian
Affiliation:
Keywords: 4-benzylidene-3, 5-isoxazolidinedione, docking, HFD- low STZ model, hypoglycemic activity , Knoevenagel condensation
Abstract: With a view to develop novel non-TZD anti-diabetic compounds, series of isoxazolidinediones were designed to target the PPAR-γ receptors. Docking studies were performed on co-crystallized protein structure of rosiglitazone with PPAR-γ receptor obtained from Protein Data Bank (2PRG). Interactions similar to that of rosiglitazone were observed for three molecules; 3a, 3b and 3c which were further synthesized and subjected to in vivo hypoglycemic, total cholesterol (CHL) and triglyceride (TG) evaluation. 14 days treatment revealed significant reduction in blood glucose levels but did not portray desirable results in terms of total CHL and TG lowering effect. The blood glucose reduction observed for 3a, 3b and 3c at 20 mg/kg/day was 53.96 %, 61.35%, 61.32% respectively as against 59.95% of the standard pioglitazone at 10mg/kg/day.
Export Options
About this article
Cite this article as:
Jadhav Rupali, Gupta-Rajoria Ranu, Pal Tanushree and Chelakara Subramanian Ramaa, Design, Synthesis and In-vivo Hypoglycemic Evaluation of Novel Non - TZD’S in a Type - 2 Diabetic Model, Medicinal Chemistry 2013; 9 (1) . https://dx.doi.org/10.2174/1573406411309010104
DOI https://dx.doi.org/10.2174/1573406411309010104 |
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
-
Combination Therapies of DPP4 Inhibitors and GLP1 Analogues with Insulin in Type 2 Diabetic Patients: A Systematic Review
Current Vascular Pharmacology Capsaicin-Sensitive Nociceptive Innervation of the Dura Mater: Implications for the Pathomechanism of Headache
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Systemic Approach to the Study of Complex Bone Disorders at the Whole- Genome Level
Current Genomics Atherogenic Index of Plasma is Associated with Body Fat Level in Type 2 Diabetes Mellitus Patients
Current Vascular Pharmacology Gene-Diet Interactions in Childhood Obesity
Current Genomics Flow Cytometry Study of Leukocyte Function: Analytical Comparison of Methods and their Applicability to Clinical Research
Current Medicinal Chemistry Thrombophilia in Pregnancy: Maternal and Fetal Implications
Current Women`s Health Reviews Smooth Muscle Cell Pathophysiology and Advanced Glycation End Products (AGEs)
Current Drug Targets SARS: Understanding the Virus and Development of Rational Therapy
Current Molecular Medicine Masked Hypertension and Diabetes
Current Hypertension Reviews Lipopolysaccharide-Induced Chorioamnionitis Causes Acute Inflammatory Changes in the Ovine Central Nervous System
CNS & Neurological Disorders - Drug Targets Endothelial Dysfunction and Atherosclerosis: Focus on Novel Therapeutic Approaches
Recent Patents on Cardiovascular Drug Discovery Thymosin β4 Protein Therapy for Cardiac Repair
Current Pharmaceutical Design Chitosan and Its Use in Design of Insulin Delivery System
Recent Patents on Drug Delivery & Formulation Mitochondrial Dysfunction and Its Relationship with mTOR Signaling and Oxidative Damage in Autism Spectrum Disorders
Mini-Reviews in Medicinal Chemistry Literature Review: Use of Family History for Primary Paediatric Care as the Next Step Towards use of Genomics in Healthcare
Current Pediatric Reviews MR Imaging of Pancreatic Islets: Tracking Isolation, Transplantation and Function
Current Pharmaceutical Design Negative Glucocorticoid Receptor Response Elements and their Role in Glucocorticoid Action
Current Pharmaceutical Design p38 Mitogen-Activated Protein Kinase: A Critical Node Linking Insulin Resistance and Cardiovascular Diseases in Type 2 Diabetes Mellitus
Endocrine, Metabolic & Immune Disorders - Drug Targets Role of Environmental Contaminants in the Etiology of Alzheimer’s Disease: A Review
Current Alzheimer Research