<abstract xmlns="http://www.w3.org/1999/xhtml">The glyoxalase system, particularly glyoxalase-I (GLO-I), has been approved as a potential target for cancer treatment. In this study, a set of structurally diverse polyphenolic natural compounds were investigated as potential GLO-I inhibitors. Ellagic acid was found, computationally and experimentally, to be the most potent GLO-I inhibitor among the tested compounds which showed an <italic>IC</italic>50 of 0.71 mmol L−1. Its binding to the GLO-I active site seemed to be mainly driven by ionic interaction <italic>via</italic> its ionized hydroxyl groups with the central Zn ion and Lys156, along with other numerous hydrogen bonding and hydrophobic interactions. Due to its unique and rigid skeleton, it can be utilized to search for other novel and potent GLO-I inhibitors <italic>via</italic> computational approaches such as pharmacophore modeling and similarity search methods. Moreover, an inspection of the docked poses of the tested compounds showed that chlorogenic acid and dihydrocaffeic acid could be considered as lead compounds worthy of further optimization.</abstract>

The glyoxalase system, particularly glyoxalase-I (GLO-I), has been approved as a potential target for cancer treatment. In this study, a set of structurally diverse polyphenolic natural compounds were investigated as potential GLO-I inhibitors. Ellagic acid was found, computationally and experimentally, to be the most potent GLO-I inhibitor among the tested compounds which showed an IC50 of 0.71 mmol L−1. Its binding to the GLO-I active site seemed to be mainly driven by ionic interaction via its ionized hydroxyl groups with the central Zn ion and Lys156, along with other numerous hydrogen bonding and hydrophobic interactions. Due to its unique and rigid skeleton, it can be utilized to search for other novel and potent GLO-I inhibitors via computational approaches such as pharmacophore modeling and similarity search methods. Moreover, an inspection of the docked poses of the tested compounds showed that chlorogenic acid and dihydrocaffeic acid could be considered as lead compounds worthy of further optimization.

Ellagic acid: A potent glyoxalase-I inhibitor with a unique scaffold

Department of Medicinal Chemistry and Pharmacognosy, Faculty of Pharmacy

Jordan University of Science and Technology

Department of Pharmaceutical Technology, Faculty of Pharmacy

Acta Pharmaceutica

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

{"article-title":"Ellagic acid: A potent glyoxalase-I inhibitor with a unique scaffold"}

The glyoxalase system, particularly glyoxalase-I (GLO-I), has been approved as a potential target for cancer treatment. In this study, a set of structurally...

Ellagic acid: A potent glyoxalase-I inhibitor with a unique scaffold

Pubblicato online: 20 lug 2020

Pagine: 115 - 130

Accettato: 21 mar 2020

DOI: https://doi.org/10.2478/acph-2021-0005

Parole chiave
ellagic acid, glyoxalase-I, zinc-binding, anticancer, molecular docking, MM-GBMV

© 2021 Nizar A. Al-Shar’i et al., published by Sciendo

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Ellagic acid: A potent glyoxalase-I inhibitor with a unique scaffold

Pubblicato online: 20 lug 2020

Pagine: 115 - 130

Accettato: 21 mar 2020

DOI: https://doi.org/10.2478/acph-2021-0005

Parole chiaveellagic acid, glyoxalase-I, zinc-binding, anticancer, molecular docking, MM-GBMV

© 2021 Nizar A. Al-Shar’i et al., published by Sciendo

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Parole chiave
ellagic acid, glyoxalase-I, zinc-binding, anticancer, molecular docking, MM-GBMV