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.
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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 |
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