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Current Drug Discovery Technologies

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ISSN (Print): 1570-1638
ISSN (Online): 1875-6220

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Research Article

Novel Cinnamic Acid Derivatives as Potential PPARδ Agonists for Metabolic Syndrome: Design, Synthesis, Evaluation and Docking Studies

Author(s): Ajay Chauhan, Ajmer S. Grewal*, Deepti Pandita and Viney Lather

Volume 17, Issue 3, 2020

Page: [338 - 347] Pages: 10

DOI: 10.2174/1570163816666190314124543

Price: $65

Abstract

Background: Peroxisome proliferator-activated receptor (PPAR) δ is expressed universally in the entire tissues, particularly in those concerned with the lipid metabolism. PPAR δ stimulation alters body’s energy fuel preference to fat from glucose and shows up as an emerging pharmacological target for the treatment of metabolic disorders.

Methods: A new series of cinnamic acid derivatives was synthesized and evaluated for the antidiabetic and antiinflammatory activities in the animal models followed by in silico docking studies to determine the binding interactions for the best fit conformations in the binding site of the PPARδ protein.

Results: Amongst the synthesized molecules, compound 3 showed higher antidiabetic activity in oral glucose tolerance test and compound 1 showed higher antiinflammatory activity in the carrageenan induced rat paw oedema method. The in vivo study results were supported by the similar in silico molecular docking results. Most of the synthesized derivatives showed drug likeness as depicted via Lipinski’s rule of 5.

Conclusion: These molecules can serve as the early hit molecules for the discovery of safe, effective and bioavailable PPARδ agonists for the potential treatment of various metabolic disorders.

Keywords: Cinnamic acid derivatives, diabetes mellitus, inflammation, metabolic syndrome, PPARδ agonists, docking.

Graphical Abstract

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