Selective inhibition of bacterial and human topoisomerases by N-arylacyl O-sulfonated aminoglycoside derivatives.

ABSTRACT: Numerous therapeutic applications have been proposed for molecules that bind heparin-binding proteins. Development of such compounds has primarily focused on optimizing the degree and orientation of anionic groups on a scaffold, but utility of these polyanions has been diminished by their typically large size and non-specific interactions with many proteins. In this study N-arylacyl O-sulfonated aminoglycosides were synthesized and evaluated for their ability to selectively inhibit structurally similar bacterial and human topoisomerases. It is demonstrated that the structure of the aminoglycoside and of the N-arylacyl moiety imparts selective inhibition of different topoisomerases and alters mechanism. The results here outline a strategy that will be applicable to iden

SUBMITTER: Fenner AM 

PROVIDER: S-EPMC3694624 | biostudies-literature | 2013 May

REPOSITORIES: biostudies-literature