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.
Org Biomol Chem
8094 - 8105
Cell Cycle Proteins, Dose-Response Relationship, Drug, Enzyme Inhibitors, Exodeoxyribonucleases, Humans, Hydroxamic Acids, Molecular Structure, Structure-Activity Relationship