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

William Doherty, Eva-Maria Dürr, Hannah T. Baddock, Sook Y. Lee, Peter J. McHugh, Tom Brown, Mathias O. Senge, Eoin M. Scanlana, Joanna F. McGouran. Organic and Biomolecular Chemistry 17, 8094-8105, 2019.

Abstract

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.