Article Sidebar
Views PDF: 3
Screening Vietnamese plants-derived natural compounds as dipeptidyl peptidase iv inhibitors for the treatment and prevention of type ii diabetes using in silico methods
Main Article Content
Abstract
Objective: To screen Vietnamse medicinal plants-derived compounds as dipeptidyl peptidase (DPP4) inhibitors with promising anti-diabetic treatment effect by in silico method.
Subjects and methods: Vietnamese medicinal plants-derived compounds were screened for the inhibiting effect on DPP4 by molecular docking methods using Autodock vina 1.2.0 and ICM pro 3.8 softwares. Pharmacokinetic and toxic properties were then examined for potential active compounds.
Results: This study showed that 11 potential natural compounds were able to inhibit DPP4. Among them, 4 compounds were the best inhibitors, including eriodictyol (–23,31 kCal/mol), luteolin (–23,71 kCal/mol), cirsimaritin (–23,47 kCal/mol) and naringenin (–27,81 kCal/mol). These four compounds showed poor permeability and solubility, were excreted in urine (> 70%), were able to inhibit CYP1A2, CYP3A4, CYP2C9 and had no toxicity on organs.
Conclusion: From the database of Vietnamese medicinal plants-derived compounds, 11 compounds were predicted to have good interactions with the DPP4 target. Among them, there are 4 flavonoid compounds (eriodictyol, luteolin, naringenin and cirsimaritin) showed the most potential on the molecular target of DPP4. Therefore, experimental studies need to be conducted to further investigate the inhibitory effects of these compounds against DPP4 for the treatment and prevention of type II diabetes.
Article Details
Keywords
Diabetes, Molecular docking, Dipeptidyl peptidase IV, Natural compounds, In silico
References
2. Karagiannis T, Paschos P, et al.. Dipeptidyl peptidase-4 inhibitors for treatment of type 2 diabetes mellitus in the clinical setting: systematic review and meta-analysis. BMJ, 2012, 344, pp. e1369.
3. Jain AN. Scoring functions for protein-ligand docking. Current Protein & Peptide Science, 2006, 7(5), pp. 407-420.
4. Nguyen TTTH. Inital building a database of Vietnamese natural compounds for virtual screening (In Vietnamese), Graduation thesis, VNU University of Medicine and Pharmacy, 2017.
5. Zhang M-Q. Working with small molecules: rules-of-thumb of “drug likeness”. Methods in Molecular Biology, 2012, 803, pp. 297-307.
6. Kim D, Wang L, et al. (2R)-4-Oxo-4-[3-(Trifluoromethyl)-5,6-dihydro[1,2,4] triazolo[4,3-a]pyrazin- 7(8H)-yl]-1-(2,4,5-trifluorophenyl)butan-2-amine: A Potent, Orally Active Dipeptidyl Peptidase IV Inhibitor for the Treatment of Type 2 Diabetes. Journal of Medicinal Chemistry, 2005, 48(1), pp.141-151.
6. Schmidt JM, Miklos F. Property Distribution: Differences between Drugs, Natural Products and Molecules from Combinatorial Chemistry. Journal of Chemical Information & Computer Sciences, 2003, 43(1), pp.218-227.
7. Kwon EY, Choi MS. Dietary eriodictyol alleviates adiposity, hepatic steatosis, insulin resistance, and inflammation in diet-induced obese mice. International Journal of Molecular Sciences, 2019, 20(5), pp. 1227.
8. Den Hartogh DJ, Tsiani E. Antidiabetic Properties of Naringenin: A Citrus Fruit Polyphenol. Biomolecules, 2019, 9(3), pp. 99.
9. Zang Y, Igarashi K, et al. Anti-diabetic effects of luteolin and luteolin-7-O-glucoside on KK-A(y) mice. Bioscience, Biotechnology, and Biochemistry, 80(8), 2016, pp.1580-1586.
10. Alqudah A, Athamneh R, et al. The Emerging Importance of Cirsimaritin in Type 2 Diabetes Treatment. International Journal of Molecular Sciences, 2023, 24(6), pp. 5749.