Investigating the potential of 6-substituted 3-formyl chromone derivatives as anti-diabetic agents using in silico methods

  • Sci Rep. 2024 Jun 8;14(1):13221. doi: 10.1038/s41598-024-63237-y.
Minhaz Zabin Saif  1 ,  Nusrat Jahan Ikbal Esha  1 ,  Syeda Tasnim Quayum  1 ,  Shofiur Rahman  2 ,  Mahmoud A Al-Gawati  3 ,  Ghadah Alsowygh  3 ,  Hamad Albrithen  3  4 ,  Abdullah N Alodhayb  5  6 ,  Raymond A Poirier  7 ,  Kabir M Uddin  8
Affiliations
  • 1. Department of Biochemistry and Microbiology, North South University, Bashundhara,, Dhaka, 1217, Bangladesh.
  • 2. Biological and Environmental Sensing Research Unit, King Abdullah Institute for Nanotechnology, King Saud University, 11451, Riyadh, Saudi Arabia. [email protected].
  • 3. Biological and Environmental Sensing Research Unit, King Abdullah Institute for Nanotechnology, King Saud University, 11451, Riyadh, Saudi Arabia.
  • 4. Research Chair for Tribology, Surface, and Interface Sciences, Department of Physics and Astronomy, College of Science, King Saud University, 11451, Riyadh, Saudi Arabia.
  • 5. Biological and Environmental Sensing Research Unit, King Abdullah Institute for Nanotechnology, King Saud University, 11451, Riyadh, Saudi Arabia. [email protected].
  • 6. Research Chair for Tribology, Surface, and Interface Sciences, Department of Physics and Astronomy, College of Science, King Saud University, 11451, Riyadh, Saudi Arabia. [email protected].
  • 7. Department of Chemistry, Memorial University, St. John's, Newfoundland, A1B 3X7, Canada. [email protected].
  • 8. Department of Biochemistry and Microbiology, North South University, Bashundhara,, Dhaka, 1217, Bangladesh. [email protected].
PMID: 38851807 DOI: 10.1038/s41598-024-63237-y
Abstract

In exploring nature's potential in addressing diabetes-related conditions, this study investigates the therapeutic capabilities of 3-formyl chromone derivatives. Utilizing in silico methodologies, we focus on 6-substituted 3-formyl chromone derivatives (1-16) to assess their therapeutic potential in treating diabetes. The research examined the formyl group at the chromone's C-3 position. ADMET, biological activities, were conducted along with B3LYP calculations using 3 different basis sets. The analogues were analyzed based on their parent structure obtained from PubChem. The HOMO-LUMO gap confirmed the bioactive nature of the derivatives, NBO analysis was performed to understand the charge transfer. PASS prediction revealed that 3-formyl chromone derivatives are potent aldehyde oxidase inhibitors, Insulin inhibitors, HIF1A expression inhibitors, and histidine kinase. Molecular docking studies indicated that the compounds had a strong binding affinity with proteins, including CAD, BHK, IDE, HIF-α, p53, COX, and Mpro of SARS-CoV2. 6-isopropyl-3-formyl chromone (4) displayed the highest affinity for IDE, with a binding energy of - 8.5 kcal mol-1. This result outperformed the affinity of the reference standard dapagliflozin (- 7.9 kcal mol-1) as well as two Other compounds that target human IDE, namely vitexin (- 8.3 kcal mol-1) and myricetin (- 8.4 kcal mol-1). MD simulations were revealed RMSD value between 0.2 and 0.5 nm, indicating the strength of the protein-ligand complex at the active site.

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