Title:Synthesis, Docking and Evaluation of Phenylacetic Acid and Trifluoro-methylphenyl Substituted Benzamide Derivatives as Potential PPARδ Agonists
Volume: 14
Issue: 11
Author(s): Ajmer Singh Grewal, Viney Lather*, Deepti Pandita and Garima Bhayana
Affiliation:
- Department of Pharmaceutical Chemistry, JCDM College of Pharmacy, Sirsa 125055, Haryana,India
Keywords:
Benzamide derivatives, diabetes mellitus, inflammation, metabolic syndrome, phenylacetic acid derivatives,
PPARδ, PPARδ agonists.
Abstract: Background: Peroxisome proliferator-activated receptor (PPAR) δ is a type of
PPARs belonging to the steroid or nuclear hormone receptor super family. Activation of PPARδ
leads to metabolism of fat instead of glucose by body for energy requirements. PPARδ represent an
emerging pharmacological target for the treatment of metabolic syndrome (MS). Many selective
and potent PPARδ agonists had been synthesized with a potential role in the treatment of various
disorders associated with MS including type 2 diabetes and inflammation.
Objective: The present work was designed to synthesize and evaluate the antidiabetic and
anti-inflammatory activity of some newer phenylacetic acid and trifluoromethylphenyl substituted
benzamide derivatives as potential PPARδ agonists.
Methods: This work involved the synthesis of newer sulfamoyl benzamide derivatives and
their evaluation by molecular docking studies to determine the binding interactions for the best fit
conformations in the binding site of the PPARδ protein. Based on the results of the in silico studies,
the selected compounds were tested for their antidiabetic and anti-inflammatory activity in the
animal models.
Results: Amongst the synthesized molecules, compound 7 showed higher anti-diabetic activity and
compound 19 showed higher anti-inflammatory activity. The experimental results were found to be
in concordance with that of the in silico results. Most of the synthesized molecules were found to
have drug like properties as devised by Lipinski's rule of five.
Conclusion: These molecules can act as the starting hits for the design of safe, effective and
bioavailable PPARδ agonists for the potential treatment of MS and related diseases.
