Volume 8 ; Issue 2 ; in Month : July-Dec (2025) Article No : 169
Neelambari S, Satish M, Priyadharshini R, et al.

Abstract

Aim: To design, synthesize, and biologically validate novel 2,4-thiazolidinedione derivatives as potential FFAR4 modulators for the treatment of non-alcoholic fatty liver disease (NAFLD). Objective: This study aims to investigate the interactions between synthesized thiazolidinedione derivatives and the FFAR4 binding site, assess their lipid-lowering efficacy, and evaluate their safety profiles in vitro. Method: In silico molecular docking studies were conducted to identify potential interactions between the derivatives and the FFAR4 binding site, followed by the synthesis of selected compounds using conventional methods. Comprehensive physicochemical characterization was performed using UV, FTIR, NMR, and mass spectrometry. In vitro evaluations included lipid accumulation assays using hepatocyte cell lines and cytotoxicity assessments via MTT assays. Result: The docking studies revealed favourable binding affinities with key amino acid residues in FFAR4, guiding the rational design of lead compounds. The synthesized derivatives demonstrated significant lipid-lowering activity in hepatocyte cell lines, with several compounds exhibiting promising safety profiles in cytotoxicity tests. Conclusion: The results support the hypothesis that 2,4-thiazolidinedione derivatives can effectively act as FFAR4 agonists, contributing to reduced lipid accumulation in hepatocytes. This study underscores the potential of these derivatives as therapeutic agents for NAFLD, highlighting the importance of further development and clinical evaluation in addressing this critical health concern. The integrated approach utilized here provides a valuable foundation for advancing the discovery of novel FFAR4-targeted agents in the fight against metabolic liver diseases.

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