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 diverse polyphenolic natural compounds were investigated as potential GLO-I inhibitors. Ellagic acid was found, computationally and experimenta...

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Bibliographic Details
Published in:	Acta Pharmaceutica Vol. 71; no. 1; pp. 115 - 130
Main Authors:	Al-Shar’i, Nizar A., Al-Balas, Qosay A., Hassan, Mohammad A., El-Elimat, Tamam M., Aljabal, Ghazi A., Almaaytah, Ammar M.
Format:	Journal Article Paper
Language:	English
Published:	Poland Sciendo 01-03-2021 De Gruyter Poland Hrvatsko farmaceutsko društvo
Subjects:	Acids anticancer Antineoplastic Agents, Phytogenic - chemistry Antineoplastic Agents, Phytogenic - pharmacology Catalytic Domain Chlorogenic acid Computer applications Computer Simulation Ellagic acid Ellagic Acid - chemistry Ellagic Acid - pharmacology Enzyme Inhibitors - chemistry Enzyme Inhibitors - pharmacology glyoxalase-I High-Throughput Screening Assays Hydrogen Bonding Hydrophobicity Hydroxyl groups Inhibitors Inspection Ionic interactions Lactoylglutathione Lyase - antagonists & inhibitors Lactoylglutathione Lyase - chemistry Lead compounds Ligands MM-GBMV Models, Molecular molecular docking Molecular Docking Simulation Molecular Structure Optimization Structure-Activity Relationship Zinc - chemistry zinc binding MM-GBMV zinc-binding molecular docking ellagic acid anticancer glyoxalase-I
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Summary:	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 of 0.71 mmol L . Its binding to the GLO-I active site seemed to be mainly driven by ionic interaction 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 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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 236084
ISSN:	1846-9558 1330-0075 1846-9558
DOI:	10.2478/acph-2021-0005