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

Oliver Orban; Ricarda S Korn; Diego Benítez; Andrea Medeiros; Lutz Preu; Nadège Loaëc; Laurent Meijer; Oliver Koch; Marcelo A Comini; Conrad Kunick

doi:10.1016/j.bmc.2016.06.023

Journal articles

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

Oliver Orban ¹ Ricarda S Korn ¹ Diego Benítez ² Andrea Medeiros ^{2, 3} Lutz Preu ¹ Nadège Loaëc ⁴ Laurent Meijer ⁴ Oliver Koch ^{5, 6} Marcelo A Comini ^{2, *} Conrad Kunick ^{1, *}

* Corresponding author

1 Technische Universität Braunschweig [Braunschweig]

2 Institut Pasteur de Montevideo

3 Departamento de Bioquímica, Facultad de Medicina

4 ManRos Therapeutics

5 Faculty of Chemistry and Chemical Biology, TU Dortmund University, Otto-Hahn-Straße 6, 44227 Dortmund, Germany.

6 Faculty of Chemistry and Chemical Biology

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.

Keywords : Trypanosomiasis Trypanothione synthetase Leishmaniasis Neglected tropical diseases Paullone Trypanosoma brucei

Document type :

Journal articles

Domain :

Life Sciences [q-bio]

Life Sciences [q-bio] / Microbiology and Parasitology

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

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

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