Understanding the Pharmacokinetic Effect of Aspartame and Nateglinide Against Hydrolase: An Insilico Study
Keywords:
Aspartame. Nateglinide. Molecular docking. Hydrolase. NateglinideAbstract
This study is performed to understand the pharmacokinetic effect of aspartame over nateglinide by an insilico approach. Virtual screening was performed for the analogues of aspartame and nateglinide against the hydrolase enzyme (3BER) involved in the metabolism the drugs using AUTO DOCK/GOLD. Molecular docking was used to evaluate a competitive interaction study of analogues. The results reviled that the amino acids THR75, THR70 and TRP44 of the active site contributed for the hydrogen bond interaction with both analogous. Aspartame analogues m843_10 and nateglinide analogues m49_2 showed the highest binding energy generating the highest F-Score of -73.94 kcal/moland -54.59kcal/mol respectively. It can be concluded that interaction profile providea roadmap that analogues interact with the same binding site and act as a competitive inhibitor leading to less hypoglycemic effect and thus it’s hypothesis that nateglinide should not be taken along with the artificial sweetener aspartame resulting in leading to low hypoglycemic activity.
References
1. Meng, X. Y., Zhang, H. X., Mezei, M., & Cui, M. (2011). Molecular docking: a powerful approach for structure-based drug discovery. Current computer-aided drug design, 7(2), 146-157. https://doi.org/10.2174/157340911795677602
2. Rycerz, K., & Jaworska-Adamu, J. E. (2013). Effects of aspartame metabolites on astrocytes and neurons. Folia neuropathologica, 51(1), 10-17. https://doi.org/10.5114/fn.2013.34191.
3. Choudhary, A. K. (2018). Aspartame: should individuals with type II diabetes be taking it?. Current diabetes reviews, 14(4), 350-362. https://doi.org/10.2174/1573399813666170601093336
4. N.C. Santos, L.M. de Araujo, G. De Luca Canto, E.N.S. Guerra, M.S. Coelho, M. de F. Borin, Metabolic effects of aspartame in adulthood: A systematic review and meta-analysis of randomized clinical trials., Crit. Rev. Food Sci. Nutr. 58 (2018) 2068–2081. https://doi.org/10.1080/10408398.2017.1304358.
5. Jones, G., Willett, P., Glen, R. C., Leach, A. R., & Taylor, R. (1997). Development and validation of a genetic algorithm for flexible docking. Journal of molecular biology, 267(3), 727-748. https://doi.org/https://doi.org/10.1006/jmbi.1996.0897
6. Khalaf, R. A., Sabbah, D., Al-Shalabi, E., Al-Sheikh, I., Albadawi, G., & Abu Sheikha, G. (2018). Synthesis, structural characterization and docking studies of sulfamoyl-phenyl acid esters as dipeptidyl peptidase-IV inhibitors. Current Computer-Aided Drug Design, 14(2), 142-151. https://doi.org/10.2174/1573409914666180308164013.
7. Wang, G., Chen, M., Wang, J., Peng, Y., Li, L., Xie, Z., ... & Li, W. (2017). Synthesis, biological evaluation and molecular docking studies of chromone hydrazone derivatives as α-glucosidase inhibitors. Bioorganic & Medicinal Chemistry Letters, 27(13), 2957-2961. https://doi.org/10.1016/j.bmcl.2017.05.007
8. Bustanji, Y., Taha, M. O., Almasri, I. M., Al-Ghussein, M. A., Mohammad, M. K., & Alkhatib, H. S. (2009). Inhibition of glycogen synthase kinase by curcumin: Investigation by simulated molecular docking and subsequent in vitro/in vivo evaluation. Journal of enzyme inhibition and medicinal chemistry, 24(3), 771-778. https://doi.org/10.1080/14756360802364377.
9. Manimaran, D., Ghanendra, S., Sridhar, M., Kaliaperumal, J., Muniyaraj, S., Mohankumar, T., ... & Elangovan, N. (2019). Molecular insights of newly identified potential peptide inhibitors of hypoxia inducible factor 1α causing breast cancer. Journal of Molecular Structure, 1177, 558-563.
10. Weaver, M. L., Orwig, B. A., Rodriguez, L. C., Graham, E. D., Chin, J. A., Shapiro, M. J., ... & Mangold, J. B. (2001). Pharmacokinetics and metabolism of nateglinide in humans. Drug metabolism and disposition, 29(4), 415-421.
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Copyright (c) 2026 Dharmar Manimaran, N.Somasundra Vengadase, Vasan Palanisamy, Kanthasamy Karthikeyan (Author)
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