Chemistry

Comparing hydrazine-derived reactive groups as inhibitors of quinone-dependent amine oxidases

Document Type

Article

Abstract

Lysyl oxidase has emerged as an important enzyme in cancer metastasis. Its activity has been reported to become upregulated in several types of cancer, and blocking its activity has been shown to limit the metastatic potential of various cancers. The small-molecules phenylhydrazine and β-aminopropionitrile are known to inhibit lysyl oxidase; however, issues of stability, toxicity, and poorly defined mechanisms limit their potential use in medical applications. The experiments presented herein evaluate three other families of hydrazine-derived compounds–hydrazides, alkyl hydrazines, and semicarbazides–as irreversible inhibitors of lysyl oxidase including determining the kinetic parameters and comparing the inhibition selectivities for lysyl oxidase against the topaquinone-containing diamine oxidase from lentil seedlings. The results suggest that the hydrazide group may be a useful core functionality that can be developed into potent and selective inhibitors of lysyl oxidase and eventually find application in cancer metastasis research.

Publication Title

Journal of Enzyme Inhibition and Medicinal Chemistry

Publication Date

2017

Volume

32

Issue

1

First Page

496

Last Page

503

ISSN

1475-6366

DOI

10.1080/14756366.2016.1265518

Keywords

enzyme kinetics, hydrazine, irreversible inhibition, Lysyl oxidase

Cross Post Location

Student Publications

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