1. Revisiting the dipeptidyl carboxypeptidase inhibitor captopril as a source of pan anti-trypanosomatid agents.
- Author
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Garsi JB, Hocine S, Hensienne R, Moitessier M, Denton H, Major LL, Smith TK, and Hanessian S
- Subjects
- Structure-Activity Relationship, Molecular Docking Simulation, Trypanocidal Agents pharmacology, Trypanocidal Agents chemistry, Trypanocidal Agents chemical synthesis, Molecular Structure, Leishmania drug effects, Leishmania enzymology, Antiprotozoal Agents pharmacology, Antiprotozoal Agents chemistry, Antiprotozoal Agents chemical synthesis, Humans, Captopril pharmacology, Captopril chemistry, Captopril chemical synthesis, Trypanosoma brucei brucei drug effects, Trypanosoma brucei brucei enzymology, Trypanosoma cruzi drug effects, Trypanosoma cruzi enzymology
- 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., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Terry K. Smith reports financial support was provided by UKRI Medical Research Council. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)
- Published
- 2024
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