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Mini-Reviews in Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1389-5575
ISSN (Online): 1875-5607

Review Article

Recent Advances in Glyoxalase-I Inhibition

Author(s): Qosay A. Al-Balas*, Mohammad A. Hassan, Nizar A. Al-Shar'i*, Ghazi A. Al Jabal and Ammar M. Almaaytah

Volume 19, Issue 4, 2019

Page: [281 - 291] Pages: 11

DOI: 10.2174/1389557518666181009141231

Price: $65

Abstract

Glyoxalase system is a ubiquitous system in human cells which has been examined thoroughly for its role in different disease conditions. It is composed of Glyoxalase-I (Glo-I) and Glyoxalase- II which perform an essential metabolic process inside the cell by detoxifying endogenous harmful metabolites, mainly methylglyoxal (MG) into non-toxic D-lactic acid. Tumor cells are well-known for their high metabolic rate which results in elevated levels of toxic metabolites. The over-expression of Glo-I in tumor cells makes this enzyme a pivotal target for anticancer drug development. Glo-I is metalloenzyme with two polypeptide chains and encompasses two active sites with an integral zinc atoms at their center. This review aims to highlight the important role of Glo-I in different pathogenic conditions, and more importantly, it provides a thorough discussion of all known human Glo-I inhibitors since its discovery, a hundred years ago, up to date. It embraces the different classes they belong to, their design and chemical structures. We believe this review will help guide the design of novel and potent human Glo-I inhibitors by providing a handy reference for interested researchers in this target.

Keywords: Human glyoxalase-I, metalloenzyme, pathogenesis, inhibitors, zinc-binding, GSH.

Graphical Abstract

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