Efficient Dimerization Disruption of Leishmania infantum Trypanothione Reductase by Triazole-phenyl-thiazoles.

ABSTRACT: Inhibition of Leishmania infantum trypanothione disulfide reductase (LiTryR) by disruption of its homodimeric interface has proved to be an alternative and unexploited strategy in the search for novel antileishmanial agents. Proof of concept was first obtained by peptides and peptidomimetics. Building on previously reported dimerization disruptors containing an imidazole-phenyl-thiazole scaffold, we now report a new 1,2,3-triazole-based chemotype that yields noncompetitive, slow-binding inhibitors of LiTryR. Several compounds bearing (poly)aromatic substituents dramatically improve the ability to disrupt LiTryR dimerization relative to reference imidazoles. Molecular modeling studies identified an almost unexplored hydrophobic region at the interfacial domain as

SUBMITTER: Revuelto A 

PROVIDER: S-EPMC8480782 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature