Insights into Thiazolidinedione Analogues: Unveiling Antioxidant Activity through Descriptor-Based Quantitative Structure-Activity Relationship Investigations

Background: Diabetes mellitus, a chronic metabolic disorder is characterized by defective insulin secretion (β-cell dysfunction), insulin action (insulin resistance) and reduced bio-antioxidant potential. Antioxidants play key role in diabetes by reducing the oxidative stress and alleviating diabetic complications. Thiazolidinediones (TZDs) attenuate insulin resistance and produce antioxidant effect.

Study Design: In continuation of our goal to develop thiazolidine-2,4-dione analogues that can address both oxidative stress and Type 2 diabetes, the in vitro antioxidant potential of a few synthesized thiazolidinediones (1-61) were evaluated for their DPPH and nitric oxide free radical scavenging assays. Descriptor-based QSAR analysis was utilized to study the structural contribution to the radical scavenging potential.

Results: Among all test compounds, the DPPH radical scavenging activity of compound 12 was found to be significant (IC50 22.7±0.43 μM). The compound 11 (IC50: 13.8±0.5 μM) showed superior nitric oxide radical scavenging potential, when compared to ascorbic acid (IC50: 14.8±0.7 µM). Among various developed QSAR models, 16 and 29 models were found to be best for DPPH and nitric oxide radical scavenging activities, respectively. The R2 value 0.745 and 0.890 in the above models are indicative of good correlation between in vitro and in silico antioxidant activity.

Conclusion: The QSAR studies revealed the potential contribution of the partition-coefficient, hydrogen bond acceptor and donors and molecular weight towards the antioxidant activity in both the assay models.