A hydroxamic-acid-containing nucleoside inhibits DNA repair nuclease SNM1A

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. Modified thymidine incorporating zinc-binding pharmacophores offers a novel approach for inhibitor development of SNM1A using rationally designed nucleoside derived inhibitors.