Bioactive Supra Decorated Thiazolidine-4-carboxylic acid derivative attenuates cellular oxidative stress by enhancing catalase activity.
A pharmacophoric motif decorated with supramolecular functionalities (TZT) was designed for potential interaction with biological targets. Main insights of this work are correlation of supra functionalities and binding ability of TZT to restructure proteins for bioactivity modulation as promising perspective in the field of cellular protection from oxidative stress. To investigate bio-availabity and role of TZT in obliterating oxidative stress at molecular level, its binding propensity with Bovine serum albumin (BSA) and Catalase (BLC) was characterized by various biophysical methods. The binding constants of TZT with BSA (Kb= 2.09×105 M-1) and BLC (Kb= 2.349×105 M-1) indicate its considerable interaction with these proteins. TZT efficiently triggers favourable structural changes in BLC, thereby enhancing its enzyme activity in a dose dependent manner. The enzyme kinetics parameters of TZT binding to BLC were quantified using Michaelis–Menten model. The molecular docking results and experimental trend of Km values suggest increased substrate availability as possible reason of enhanced BLC activity. Furthermore, physiological relevance of this interaction was investigated by ability of TZT to attenuate oxidative stress induced inhibition of cell proliferation. Treatment with TZT led to reversal of inhibition in A549 cell proliferation effectuated by high concentrations of vitamin C. At molecular level, TZT was found to inhibit apoptotic cell death induced by accumulation of hydrogen peroxide as evaluated from PARP cleavage status.