In vitro and in silico studies of fluorinated 2, 3‐disubstituted thiazolidinone‐pyrazoles as potential α‐amylase inhibitors and antioxidant agents. Issue 3 (19th December 2021)

• Record Type: Journal Article
• Authors: Ganavi, Devaraj; Ramu, Ramith; Kumar, Vasantha; Patil, Shashank M.; Martiz, Reshma M.; Shirahatti, Prithvi S.; Sathyanarayana, Reshma; Poojary, Boja; Holla, B. Shivarama; Poojary, Vishwanatha; Kumari, K. P. Nanda; Shivachandra, Jagadeep Chandra
• Is Part Of: Archiv der Pharmazie. Volume 355:Issue 3(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2021-12-19
• Subjects: antioxidant -- enzyme kinetics -- molecular docking -- pyrazole aldehydes -- thiazolidin‐4‐ones -- α‐amylase inhibition; Pharmaceutical chemistry -- Periodicals; Pharmacology -- Periodicals; 615.19
• DOI: 10.1002/ardp.202100342
• Languages: English
• ISSNs: 0365-6233

Abstract

Abstract: As part of our effort to identify potent α‐amylase inhibitors, in the present study, a novel series of fluorinated thiazolidinone‐pyrazole hybrid molecules were prepared by the condensation of 3‐(aryl/benzyloxyaryl)‐pyrazole‐4‐carbaldehydes with fluorinated 2, 3‐disubstituted thiazolidin‐4‐ones. The structures of the newly synthesized compounds were confirmed by infrared, 1 H nuclear magnetic resonance (NMR), 13 C NMR, and liquid chromatography–mass spectrometry data. All the compounds were screened for their α‐amylase inhibitory and free radical scavenging activities by DPPH (1, 1‐diphenyl‐2‐picrylhydrazyl) and ABTS methods. Among the tested compounds, compound 8g emerged as a promising α‐amylase inhibitor with IC50 = 0.76 ± 1.23 µM, and it was found to be more potent than the standard drug acarbose (IC50 = 0.86 ± 0.81 μM). Compounds 8b and 8g showed strong free radical scavenging activity compared to the standard butylated hydroxyl anisole. The kinetic study of compound 8g revealed the reversible, classical competitive inhibition mode on the α‐amylase enzyme. Molecular docking and dynamic simulations studies were performed for the most potent compound 8g, which displayed remarkable hydrogen bonding with the α‐amylase protein (PDB ID: 1DHK). Abstract : Novel fluorinated thiazolidinone‐pyrazole hybrid molecules were prepared and tested as α‐amylase inhibitors and free radical‐scavenging agents. Compound 8g emerged as a promising α‐amylase inhibitor that was more potent than the standard drug acarbose. Compounds 8b and 8g showed strong free radical‐scavenging activity. Molecular docking revealed remarkable hydrogen bonding of compound 8g with the α‐amylase protein.