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

  • Bioorg Chem. 2020 Nov:104:104238. doi: 10.1016/j.bioorg.2020.104238.
Irfan Ali  1 ,  Rafaila Rafique  1 ,  Khalid Mohammed Khan  2 ,  Sridevi Chigurupati  3 ,  Xingyue Ji  4 ,  Abdul Wadood  5 ,  Ashfaq Ur Rehman  5 ,  Uzma Salar  6 ,  Muhammad Shahid Iqbal  7 ,  Muhammad Taha  8 ,  Shahnaz Perveen  9 ,  Basharat Ali  1
Affiliations
  • 1. H. E. J. Research Institute of Chemistry, International Center for Chemical and Biological, Sciences, University of Karachi, Karachi 75270, Pakistan.
  • 2. H. E. J. Research Institute of Chemistry, International Center for Chemical and Biological, Sciences, University of Karachi, Karachi 75270, Pakistan; Department of Clinical Pharmacy, Institute for Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, P.O. Box 31441, Dammam, Saudi Arabia. Electronic address: [email protected].
  • 3. Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, Qassim University, Buraidah 52571, Saudi Arabia.
  • 4. Department of Medicinal Chemistry, College of Pharmaceutical Science, Soochow University, Suzhou, China.
  • 5. Department of Biochemistry, Shankar Campus, Abdul Wali Khan University, Mardan, Khyber Pukhtoonkhwa, Pakistan.
  • 6. Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan.
  • 7. Department of Clinical Pharmacy, College of Pharmacy, Prince Sattam bin Abdulaziz University, Alkharj, Saudi Arabia.
  • 8. Department of Clinical Pharmacy, Institute for Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, P.O. Box 31441, Dammam, Saudi Arabia.
  • 9. PCSIR Laboratories Complex, Karachi, Shahrah-e-Dr. Salimuzzaman Siddiqui, Karachi 75280, Pakistan.
PMID: 32911195 DOI: 10.1016/j.bioorg.2020.104238
Abstract

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.

Keywords
ABTS; Benzofuran; DPPH; Docking studies; In vitro; Kinetics; Radical scavengers; Synthesis; α-amylase.
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