Version 1
: Received: 26 August 2024 / Approved: 27 August 2024 / Online: 28 August 2024 (09:37:19 CEST)
How to cite:
Rebai, R.; Jasmin, L.; Boudah, A. Identification of Two Flavonoids as New and Safe Inhibitors of Kynurenine Aminotransferase II via Computational and In Vitro Study. Preprints2024, 2024082012. https://doi.org/10.20944/preprints202408.2012.v1
Rebai, R.; Jasmin, L.; Boudah, A. Identification of Two Flavonoids as New and Safe Inhibitors of Kynurenine Aminotransferase II via Computational and In Vitro Study. Preprints 2024, 2024082012. https://doi.org/10.20944/preprints202408.2012.v1
Rebai, R.; Jasmin, L.; Boudah, A. Identification of Two Flavonoids as New and Safe Inhibitors of Kynurenine Aminotransferase II via Computational and In Vitro Study. Preprints2024, 2024082012. https://doi.org/10.20944/preprints202408.2012.v1
APA Style
Rebai, R., Jasmin, L., & Boudah, A. (2024). Identification of Two Flavonoids as New and Safe Inhibitors of Kynurenine Aminotransferase II via Computational and In Vitro Study. Preprints. https://doi.org/10.20944/preprints202408.2012.v1
Chicago/Turabian Style
Rebai, R., Luc Jasmin and Abdennacer Boudah. 2024 "Identification of Two Flavonoids as New and Safe Inhibitors of Kynurenine Aminotransferase II via Computational and In Vitro Study" Preprints. https://doi.org/10.20944/preprints202408.2012.v1
Abstract
The inhibition of kynurenine aminotransferase II (KATII) is a target for treating several diseases with an excess of kynurenic acid (KYNA). KATII inhibitors exist, but they have adverse side effects, given their irreversible inhibition mechanism. This study aimed to discover potent and safe inhibitors of KATII by using computational and in vitro methods. We identified herbacetin and (-)-Epicatechin as reversible KATII inhibitors from a small library of natural compounds, whose Glide docking scores (-8.66 kcal mol-1 and-8.16 kcal mol-1, respectively) and MM/GBSA binding energies (-50.30 kcal mol-1 and -51.35 kcal mol-1, respectively), which are higher scores than the standard inhibitor, PF-04859989 (-7.12 kcal mol-1 and -38.41 kcal mol-1, respectively). The ADMET analysis showed that herbacetin and (-)-Epicatechin have suitable pharmacokinetic parameters, are moderately bioavailable, and have a safe toxicity profile. Their KATII inhibitory activity is in the range of IC50 values of 5.98± 0.18 µM and 8.76 ± 0.76 µM, respectively. Furthermore, the MTT assay for cell toxicity showed that the two compounds do not alter HepG2 cell viability at their required concentration for KATII inhibition. These results show that herbacetin and(-)-Epicatechin are suitable for KATII inhibition and appropriate candidates for further development of KATII inhibitors.
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
