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Nine modified nucleosides, incorporating zinc-binding pharmacophores, have been synthesised and evaluated as inhibitors of the DNA repair nuclease SNM1A. The series included oxyamides, hydroxamic acids, hydroxamates, a hydrazide, a squarate ester and a squaramide. A hydroxamic acid-derived nucleoside inhibited the enzyme, offering a novel approach for potential therapeutic development through the use of rationally designed nucleoside derived inhibitors.

Original publication

DOI

10.1039/c9ob01133a

Type

Journal article

Journal

Org Biomol Chem

Publication Date

21/09/2019

Volume

17

Pages

8094 - 8105

Keywords

Cell Cycle Proteins, Dose-Response Relationship, Drug, Enzyme Inhibitors, Exodeoxyribonucleases, Humans, Hydroxamic Acids, Molecular Structure, Structure-Activity Relationship