Development of Novel Glitazones as Antidiabetic Agents: Molecular Design, Synthesis, Evaluation of Glucose Uptake Activity and SAR Studies

Author(s): Mahendra Gowdru Srinivas, Prabitha Prabhakaran, Subhankar Probhat Mandal, Yuvaraj Sivamani, Pranesh Guddur, Bommenahally Ravanappa Prashantha Kumar*.

Journal Name: Letters in Drug Design & Discovery

Volume 17 , Issue 7 , 2020

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Background: Thiazolidinediones and its bioisostere, namely, rhodanines have become ubiquitous class of heterocyclic compounds in drug design and discovery. In the present study, as part of molecular design, a series of novel glitazones that are feasible to synthesize in our laboratory were subjected to docking studies against PPAR-γ receptor for their selection.

Methods and Results: As part of the synthesis of selected twelve glitazones, the core moiety, pyridine incorporated rhodanine was synthesized via dithiocarbamate. Later, a series of glitazones were prepared via Knovenageal condensation. In silico docking studies were performed against PPARᵧ protein (2PRG). The titled compounds were investigated for their cytotoxic activity against 3T3-L1 cells to identify the cytotoxicity window of the glitazones. Further, within the cytotoxicity window, glitazones were screened for glucose uptake activity against L6 cells to assess their possible antidiabetic activity.

Conclusion: Based on the glucose uptake results, structure activity relationships are drawn for the title compounds.

Keywords: Rhodanines, glitazones, Type 2 diabetes mellitus, glucose uptake, L6 cells, SAR.

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Article Details

Year: 2020
Page: [840 - 849]
Pages: 10
DOI: 10.2174/1570180816666191105124535
Price: $95

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