α-Glucosidase Inhibitory Activity of Prenylated Pyranocoumarins from Clausena excavata: Mechanism of Action, ADMET and Molecular Docking.

Autor: Promden W; Division of General Science, Faculty of Education, Buriram Rajabhat University, Buriram, 31000, Thailand., Lophaet A; Division of General Science, Faculty of Education, Buriram Rajabhat University, Buriram, 31000, Thailand., Sripadung P; Integrative Pharmaceuticals and Innovative of Pharmaceutical Technology Research Unit, Faculty of Pharmacy, Mahasarakham University, Khamriang, Kantarawichai, Maha Sarakham, 44150, Thailand., Sungthong B; Integrative Pharmaceuticals and Innovative of Pharmaceutical Technology Research Unit, Faculty of Pharmacy, Mahasarakham University, Khamriang, Kantarawichai, Maha Sarakham, 44150, Thailand., Samsee T; Department of Chemistry and Center of Excellence for Innovation in Chemistry (PERCH-CIC), Faculty of Science, Mahasarakham University, Khamriang, Kantarawichai, Maha Sarakham, 44150, Thailand., Ploylearmsang C; Social Pharmacy Research Unit, Faculty of Pharmacy, Mahasarakham University, Khamriang, Kantarawichai, Maha Sarakham, 44150, Thailand., Kijjoa A; Instituto de Ciências Biomédicas Abel Salazar and CIIMAR, Universidade do Porto, Rua de Jorge Viterbo Ferreira, 228, 4050-313, Porto, Portugal., Seephonkai P; Department of Chemistry and Center of Excellence for Innovation in Chemistry (PERCH-CIC), Faculty of Science, Mahasarakham University, Khamriang, Kantarawichai, Maha Sarakham, 44150, Thailand.
Jazyk: angličtina
Zdroj: Chemistry & biodiversity [Chem Biodivers] 2024 Sep; Vol. 21 (9), pp. e202401141. Date of Electronic Publication: 2024 Aug 07.
DOI: 10.1002/cbdv.202401141
Abstrakt: Three naturally occurring prenylated pyranocoumarins, nordentatin (1), dentatin (2), and clausarin (3), isolated from the roots of Clausena excavata (Family Rutaceae), and O-methylclausarin (4) which was obtained by methylation of 3, were investigated for their α-glucosidase inhibitory activity. The mechanism of action and the in silico prediction of their physicochemical and ADMET properties as well as the molecular docking were also studied. Compounds 1-4 exhibited stronger α-glucosidase inhibitory activity than the positive control, acarbose, through a non-competitive mechanism. Among them, 3 exhibited the highest activity, with an IC 50 of 8.36 μM, which is significantly stronger than that of acarbose (IC 50 =430.35 μM). The prenyl group on C-3 and the hydroxyl group on C-5 in 3 may play important roles in enhancing the activity. Calculated physicochemical and ADMET parameters of 1-4 satisfied the Lipinski's and Veber's rules. Molecular simulation analysis indicated they are promising drug candidates with no hepatotoxicity. Compound 3 exhibited potent activity in the experiment and demonstrated good drug properties based on the calculations. A molecular docking study revealed that 3 showed H-bonding and π-π stacking interactions with selective Phe321, as well as interactions with thirteen other amino acid residues of the α-glucosidase.
(© 2024 Wiley-VHCA AG, Zurich, Switzerland.)
Databáze: MEDLINE
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