Back to Search
Start Over
Synthesis, biological activities, and evaluation molecular docking-dynamics studies of new phenylisoxazole quinoxalin-2-amine hybrids as potential α-amylase and α-glucosidase inhibitors.
- Source :
-
RSC advances [RSC Adv] 2024 Mar 05; Vol. 14 (11), pp. 7684-7698. Date of Electronic Publication: 2024 Mar 05 (Print Publication: 2024). - Publication Year :
- 2024
-
Abstract
- New phenylisoxazole quinoxalin-2-amine hybrids 5a-i were successfully synthesised with yields of 53-85% and characterised with various spectroscopy methods. The synthesised hybrids underwent in vitro α-amylase and α-glucosidase inhibitory assays, with acarbose as the positive control. Through the biological study, compound 5h exhibits the highest α-amylase inhibitory activity with IC <subscript>50</subscript> = 16.4 ± 0.1 μM while compounds 5a-c, 5e and 5h exhibit great potential as α-glucosidase inhibitors, with 5c being the most potent (IC <subscript>50</subscript> = 15.2 ± 0.3 μM). Among the compounds, 5h exhibits potential as a dual inhibitor for both α-amylase (IC <subscript>50</subscript> = 16.4 ± 0.1 μM) and α-glucosidase (IC <subscript>50</subscript> = 31.6 ± 0.4 μM) enzymes. Through the molecular docking studies, the inhibition potential of the selected compounds is supported. Compound 5h showed important interactions with α-amylase enzyme active sites and exhibited the highest binding energy of -8.9 ± 0.10 kcal mol <superscript>-1</superscript> , while compound 5c exhibited the highest binding energy of -9.0 ± 0.20 kcal mol <superscript>-1</superscript> by forming important interactions with the α-glucosidase enzyme active sites. The molecular dynamics study showed that the selected compounds exhibited relative stability when binding with α-amylase and α-glucosidase enzymes. Additionally, compound 5h demonstrated a similar pattern of motion and mechanism of action as the commercially available miglitol.<br />Competing Interests: The authors declare no conflict of interest.<br /> (This journal is © The Royal Society of Chemistry.)
Details
- Language :
- English
- ISSN :
- 2046-2069
- Volume :
- 14
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- RSC advances
- Publication Type :
- Academic Journal
- Accession number :
- 38444963
- Full Text :
- https://doi.org/10.1039/d3ra08642a