Issue 10, 2022

Hydroxypyrone derivatives in drug discovery: from chelation therapy to rational design of metalloenzyme inhibitors

Abstract

The versatile structural motif of hydroxypyrone is found in natural products and can be easily converted into hydroxypyridone and hydroxythiopyridone analogues. The favourable toxicity profile and ease of functionalization to access a vast library of compounds make them an ideal structural scaffold for drug design and discovery. This versatile scaffold possesses excellent metal chelating properties that can be exploited for chelation therapy in clinics. Deferiprone [1,2-dimethyl-3-hydroxy-4(1H)-one] was the first orally active chelator to treat iron overload in thalassemia major. Metal complexes of hydroxy-(thio)pyr(id)ones have been investigated as magnetic resonance imaging contrast agents, and anticancer and antidiabetic agents. In recent years, this compound class has demonstrated potential in discovering and developing metalloenzyme inhibitors. This review article summarizes recent literature on hydroxy-(thio)pyr(id)ones as inhibitors for metalloenzymes such as histone deacetylases, tyrosinase and metallo-β-lactamase. Different approaches to the design of hydroxy-(thio)pyr(id)ones and their biological properties against selected metalloenzymes are discussed.

Graphical abstract: Hydroxypyrone derivatives in drug discovery: from chelation therapy to rational design of metalloenzyme inhibitors

Article information

Article type
Review Article
Submitted
10 Jūn. 2022
Accepted
28 Jūl. 2022
First published
29 Jūl. 2022

RSC Med. Chem., 2022,13, 1127-1149

Hydroxypyrone derivatives in drug discovery: from chelation therapy to rational design of metalloenzyme inhibitors

J. Z. Arshad and M. Hanif, RSC Med. Chem., 2022, 13, 1127 DOI: 10.1039/D2MD00175F

To request permission to reproduce material from this article, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements