Title:Novel Cinnamic Acid Derivatives as Potential PPARδ Agonists for Metabolic Syndrome: Design, Synthesis, Evaluation and Docking Studies
VOLUME: 17 ISSUE: 3
Author(s):Ajay Chauhan, Ajmer S. Grewal*, Deepti Pandita and Viney Lather
Affiliation:Jan Nayak Ch. Devi Lal Memorial College of Pharmacy, Sirsa, Haryana, Chitkara College of Pharmacy, Chitkara University, Punjab, Amity Institute of Molecular Medicine & Stem Cell Research, Amity University, Noida, Uttar Pradesh, Amity Institute of Pharmacy, Amity University, Noida, Uttar Pradesh
Keywords:Cinnamic acid derivatives, diabetes mellitus, inflammation, metabolic syndrome, PPARδ agonists, docking.
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.
