Zinc-Containing Metalloenzymes: Inhibition by Metal-Based Anticancer Agents

Frontiers in Chemistry
Ruirong YeZong-Wan Mao

Abstract

DNA is considered to be the primary target of platinum-based anticancer drugs which have gained great success in clinics, but DNA-targeted anticancer drugs cause serious side-effects and easily acquired drug resistance. This has stimulated the search for novel therapeutic targets. In the past few years, substantial research has demonstrated that zinc-containing metalloenzymes play a vital role in the occurrence and development of cancer, and they have been identified as alternative targets for metal-based anticancer agents. Metal complexes themselves have also exhibited a lot of appealing features for enzyme inhibition, such as: (i) the facile construction of 3D structures that can increase the enzyme-binding selectivity and affinity; (ii) the intriguing photophysical and photochemical properties, and redox activities of metal complexes can offer possibilities to design enzyme inhibitors with multiple modes of action. In this review, we discuss recent examples of zinc-containing metalloenzyme inhibition of metal-based anticancer agents, especially three zinc-containing metalloenzymes overexpressed in tumors, including histone deacetylases (HDACs), carbonic anhydrases (CAs), and matrix metalloproteinases (MMPs).

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Citations

Dec 22, 2020·ChemMedChem·Pavitra S ThackerClaudiu T Supuran
Dec 4, 2020·International Journal of Molecular Sciences·Yuxiang Luo, Huilin Li
Dec 16, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Marina PorchiaCarlo Santini
Jun 15, 2021·Chemical Science·Elizabeth J AnthonyZijin Zhang
Jul 19, 2021·European Journal of Medicinal Chemistry·Jing LiangLixia Chen

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Methods Mentioned

BETA
acetylation
histone acetylation

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