Design, synthesis, in vitro α-glucosidase inhibition, docking, and molecular dynamics of new phthalimide-benzenesulfonamide hybrids for targeting type 2 diabetes
In the present work, a new series of 14 novel phthalimide-benzenesulfonamide derivatives 4a – n were synthesized, and their inhibitory activity against yeast α-glucosidase was screened. The obtained results indicated that most of the newly synthesized compounds showed prominent inhibitory activity a...
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Veröffentlicht in: | Scientific reports 2022-06, Vol.12 (1), p.10569-16, Article 10569 |
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Hauptverfasser: | , , , , , , , , , |
Format: | Artikel |
Sprache: | eng |
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Zusammenfassung: | In the present work, a new series of 14 novel phthalimide-benzenesulfonamide derivatives
4a
–
n
were synthesized, and their inhibitory activity against yeast α-glucosidase was screened. The obtained results indicated that most of the newly synthesized compounds showed prominent inhibitory activity against α-glucosidase. Among them, 4-phenylpiperazin derivative
4m
exhibited the strongest inhibition with the IC
50
value of 52.2 ± 0.1 µM. Enzyme kinetic study of compound
4m
proved that its inhibition mode was competitive and K
i
value of this compound was calculated to be 52.7 µM. In silico induced fit docking and molecular dynamics studies were performed to further investigate the interaction, orientation, and conformation of the target compounds over the active site of α-glucosidase. Obtained date of these studies demonstrated that our new compounds interacted as well with the α-glucosidase active site with the acceptable binding energies. Furthermore, in silico druglikeness/ADME/Toxicity studies of compound
4m
were performed and predicted that this compound is druglikeness and has good ADME and toxicity profiles. |
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ISSN: | 2045-2322 2045-2322 |
DOI: | 10.1038/s41598-022-14896-2 |