2. Academic Validation
  3. Revisiting the dipeptidyl carboxypeptidase inhibitor captopril as a source of pan anti-trypanosomatid agents

Revisiting the dipeptidyl carboxypeptidase inhibitor captopril as a source of pan anti-trypanosomatid agents

  • Bioorg Med Chem Lett. 2024 Sep 15:110:129883. doi: 10.1016/j.bmcl.2024.129883.
Jean-Baptiste Garsi 1,  Sofiane Hocine 1,  Raphaël Hensienne 1,  Matthieu Moitessier 1,  Helen Denton 2,  Louise L Major 2,  Terry K Smith 3,  Stephen Hanessian 4
Affiliations

Affiliations

  • 1 Department of Chemistry, Université de Montréal, Station Centre-Ville, C.P. 6128, Montreal, QC H3C 3J7, Canada.
  • 2 Schools of Biology and Chemistry, Biomedical Sciences Research Complex, University of St. Andrews, St. Andrews, Fife, Scotland KY16 9ST, UK.
  • 3 Schools of Biology and Chemistry, Biomedical Sciences Research Complex, University of St. Andrews, St. Andrews, Fife, Scotland KY16 9ST, UK. Electronic address: [email protected].
  • 4 Department of Chemistry, Université de Montréal, Station Centre-Ville, C.P. 6128, Montreal, QC H3C 3J7, Canada. Electronic address: [email protected].
PMID: 39013490 DOI: 10.1016/j.bmcl.2024.129883
Abstract

The protozoan parasites Trypanosoma brucei, Trypanosoma cruzi and Leishmania spp. are responsible for continued propagation of neglected tropical diseases such as African sleeping sickness, Chagas disease and leishmaniasis respectively. Following a report that captopril targets Leishmania donovani dipeptidyl Carboxypeptidase, a series of simple proline amides and captopril analogues were synthesized and found to exhibit 1-2 μM in vitro inhibition and selectivity against Trypanosoma brucei, Trypanosoma cruzi and Leishmania spp. The results were corroborated with computational docking studies. Arguably, the synthetic proline amides represent the structurally simplest examples of in vitro pan antiprotozoal compounds.

Keywords

Antiprotozoal; Captopril surrogates; Proline amides; ‘big eye’ Phenotype.

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