5-Substituted 3-chlorokenpaullone derivatives are potent inhibitors of Trypanosoma brucei bloodstream forms. - RIIP - Réseau International des Instituts Pasteur Access content directly
Journal Articles Bioorganic and Medicinal Chemistry Year : 2016

5-Substituted 3-chlorokenpaullone derivatives are potent inhibitors of Trypanosoma brucei bloodstream forms.

Abstract

Trypanothione synthetase is an essential enzyme for kinetoplastid parasites which cause highly disabling and fatal diseases in humans and animals. Inspired by the observation that N(5)-substituted paullones inhibit the trypanothione synthetase from the related parasite Leishmania infantum, we designed and synthesized a series of new derivatives. Although none of the new compounds displayed strong inhibition of Trypanosoma brucei trypanothione synthetase, several of them caused a remarkable growth inhibition of cultivated Trypanosoma brucei bloodstream forms. The most potent congener 3a showed antitrypanosomal activity in double digit nanomolar concentrations and a selectivity index of three orders of magnitude versus murine macrophage cells.
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pasteur-01499026 , version 1 (09-10-2017)

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Oliver Orban, Ricarda S Korn, Diego Benítez, Andrea Medeiros, Lutz Preu, et al.. 5-Substituted 3-chlorokenpaullone derivatives are potent inhibitors of Trypanosoma brucei bloodstream forms.. Bioorganic and Medicinal Chemistry, 2016, 24 (16), pp.3790-800. ⟨10.1016/j.bmc.2016.06.023⟩. ⟨pasteur-01499026⟩
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