Investigating the potential of 6-substituted 3-formyl chromone derivatives as anti-diabetic agents using in silico methods.
Sci Rep
; 14(1): 13221, 2024 06 08.
Article
de En
| MEDLINE
| ID: mdl-38851807
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.
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
4H-1-Benzopyran-4-ones
/
Simulation de docking moléculaire
/
Hypoglycémiants
Limites:
Humans
Langue:
En
Journal:
Sci Rep
Année:
2024
Type de document:
Article
Pays d'affiliation:
Bangladesh
Pays de publication:
Royaume-Uni