Bioactive supra decorated thiazolidine-4-carboxylic acid derivatives attenuate cellular oxidative stress by enhancing catalase activity. Issue 15 (31st March 2020)

• Record Type: Journal Article
• Authors: Rizvi, Masood Ahmad; Hussain, Zakir; Ali, Fasil; Amin, Asif; Mir, Sajjad Husain; Rydzek, Gaulthier; Jagtap, Rohidas M.; Pardeshi, Satish K.; Qadri, Raies A.; Ariga, Katsuhiko
• Is Part Of: Physical chemistry chemical physics. Volume 22:Issue 15(2020)
• Page Start: 7942
• Page End: 7951
• Publication Date: 2020-03-31
• Subjects: Chemistry, Physical and theoretical -- Periodicals; 541.3
• DOI: 10.1039/d0cp00253d
• Languages: English
• ISSNs: 1463-9076

Abstract

Abstract : Bioactive (2 S, 4 R )-3-( tert -butoxycarbonyl)-2-(2-hydroxyphenyl)thiazolidine-4-carboxylic acid molecules restructure enzymes through complexation, allowing enhancing their activity to protect cells from oxidative stress. Abstract : A pharmacophoric motif decorated with supramolecular functionalities (TZT) was designed for potential interaction with biological targets. Main insights of this work include the correlation of supra functionalities of TZT with its binding ability to proteins leading to the modulation of their structure and bioactivity as a promising perspective in the field of cellular protection from oxidative stress. To investigate the role of TZT in obliterating oxidative stress at a molecular level, its binding propensity with bovine serum albumin (BSA) and bovine liver catalase (BLC) was characterized using various biophysical methods. The binding constants of TZT with BSA ( K b = 2.09 × 10 5 M −1 ) and BLC ( K b = 2.349 × 10 5 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 the Michaelis–Menten model. Both in silico and experimental results suggest that an increased substrate availability could be the reason for enhanced BLC activity. Furthermore, physiological relevance of this interaction was demonstrated by investigating the ability of TZT to attenuate oxidative stress. Treatment with TZT was found to mitigate the inhibition of A549 cell proliferation in the presence of high concentrations of vitamin C. This finding was confirmed at a molecular level by PARP cleavage status, demonstrating that TZT inhibits apoptotic cell death induced by oxidative stress.