Antitrypanosomal 8-Hydroxy-Naphthyridines Are Chelators of Divalent Transition Metals.

ABSTRACT: The lack of information regarding the mechanisms of action (MoA) or specific molecular targets of phenotypically active compounds can prove a barrier to their development as chemotherapeutic agents. Here, we report the results of our orthogonal genetic, molecular, and biochemical studies to determine the MoA of a novel 7-substituted 8-hydroxy-1,6-naphthyridine (8-HNT) series that displays promising activity against Trypanosoma brucei and Leishmania donovani High-throughput loss-of-function genetic screens in T. brucei highlighted two probable zinc transporters associated with resistance to these compounds. These transporters localized to the parasite Golgi apparatus. Directed by these findings, the role of zinc and other divalent cations in the MoA of these compounds w

SUBMITTER: Wall RJ 

PROVIDER: S-EPMC6105827 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature