Potent α-amylase inhibitors and radical (DPPH and ABTS) scavengers based on benzofuran-2-yl(phenyl)methanone derivatives: Syntheses, in vitro, kinetics, and in silico studies

• Published in: Bioorganic chemistry 2020-11, Vol.104, p.104238, Article 104238
• Main Authors: Ali, Irfan, Rafique, Rafaila, Khan, Khalid Mohammed, Chigurupati, Sridevi, Ji, Xingyue, Wadood, Abdul, Rehman, Ashfaq Ur, Salar, Uzma, Iqbal, Muhammad Shahid, Taha, Muhammad, Perveen, Shahnaz, Ali, Basharat
• Format: Article
• Language: English
• Subjects: ABTS; alpha-Amylases - antagonists & inhibitors; alpha-Amylases - metabolism; Benzofuran; Benzofurans - chemical synthesis; Benzofurans - chemistry; Benzofurans - pharmacology; Benzothiazoles - antagonists & inhibitors; Biphenyl Compounds - antagonists & inhibitors; Docking studies; Dose-Response Relationship, Drug; DPPH; Enzyme Inhibitors - chemical synthesis; Enzyme Inhibitors - chemistry; Enzyme Inhibitors - pharmacology; Free Radical Scavengers - chemical synthesis; Free Radical Scavengers - chemistry; Free Radical Scavengers - pharmacology; In vitro; Kinetics; Molecular Docking Simulation; Molecular Structure; Picrates - antagonists & inhibitors; Radical scavengers; Structure-Activity Relationship; Sulfonic Acids - antagonists & inhibitors; Synthesis; α-amylase
• ISSN: 0045-2068; 1090-2120
• DOI: 10.1016/j.bioorg.2020.104238

[Display omitted] •Synthesis of benzofuran derivatives (1-30) and fully characterized by various spectroscopic techniques.•In vitro screening against α-Amylase enzyme inhibitory and antioxidant activities.•Limited Structure-activity relationship was established to understand the contribution of different substituents.•In silico studies of most active compounds were performed to understand the binding interactions with enzyme.•Kinetic studies were performed to insight the mode of inhibition. Thirty benzofuran-2-yl(phenyl)methanones 1–30 were synthesized and characterized their structures by spectroscopic techniques. Substituted phenacyl bromide and different derivatives of 2-hydroxy-benzaldehyde treated in the presence of anhydrous K2CO3 in acetonitrile at room temperature to afford the desired benzofurans 1–30. All compounds were screened for their in vitro α-amylase inhibitory and radical scavenging (DPPH and ABTS) activities. Results revealed that para substituted compounds were found to be more active than the others with IC50 values ranges for α-amylase inhibition (IC50 = 18.04–48.33 µM), DPPH (IC50 = 16.04–32.33 µM) and ABTS (IC50 = 16.99–33.01 µM) radical scavenging activities. Activities results were compared with the standards acarbose (IC50 = 16.08 ± 0.07 µM) for α-amylase, ascorbic acid (IC50 = 15.08 ± 0.03 and 15.09 ± 0.17 µM) for DPPH and ABTS radical scavenging activities, respectively. Kinetic studies predicted that all compounds followed non-competitive mechanism of inhibition. Molecular docking results showed good protein–ligand interactions profile against the corresponding target. To the best of our knowledge, out of thirty molecules, ten compounds 18–20, 22, and 25–30 were structurally new.