Introduction of the α-ketoamide structure: en route to develop hydrogen peroxide responsive prodrugs.

ABSTRACT: Leveraging the elevated levels of hydrogen peroxide (H₂O₂) in cancer, inflammatory diseases and cardiovascular disorders, H₂O₂-activated promoieties have been widely used in drugs and biomaterials design. However, the overwhelming majority of the promoieties only share the common structure of a H₂O₂-responsive arylboronic acid/ester moiety with low diversity. We report here an unprecedented strategy to construct novel H₂O₂-responsive prodrugs based on an α-ketoamide structure. As a proof of concept, we designed and synthesized a panel of α-ketoamide based nitrogen mustard prodrugs, among which KAM-2 showed potent growth inhibitory activity and high selectivity toward cancer cells. The H₂

SUBMITTER: Meng T 

PROVIDER: S-EPMC6761880 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature