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

Jean Baptiste Garsi; Sofiane Hocine; Raphaël Hensienne; Matthieu Moitessier; Helen Denton; Louise L. Major; Terry K. Smith; Stephen Hanessian

doi:10.1016/j.bmcl.2024.129883

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

Jean Baptiste Garsi, Sofiane Hocine, Raphaël Hensienne, Matthieu Moitessier, Helen Denton, Louise L. Major, Terry K. Smith^*, Stephen Hanessian^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Article number	129883
Number of pages	12
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	110
Early online date	17 Jul 2024
DOIs	https://doi.org/10.1016/j.bmcl.2024.129883
Publication status	Published - 15 Sept 2024

Keywords

Antiprotozoal
Captopril surrogates
Proline amides
‘Big eye’ phenotype

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.bmcl.2024.129883

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title = "Revisiting the dipeptidyl carboxypeptidase inhibitor captopril as a source of pan anti-trypanosomatid agents",

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, {\textquoteleft}Big eye{\textquoteright} phenotype",

author = "Garsi, {Jean Baptiste} and Sofiane Hocine and Rapha{\"e}l Hensienne and Matthieu Moitessier and Helen Denton and Major, {Louise L.} and Smith, {Terry K.} and Stephen Hanessian",

note = "Funding: The TKS group thanks the Medical Research Council (MR/Mo20118/1) and University of St Andrews for financial support.",

year = "2024",

month = sep,

day = "15",

doi = "10.1016/j.bmcl.2024.129883",

language = "English",

volume = "110",

journal = "Bioorganic and Medicinal Chemistry Letters",

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TY - JOUR

T1 - Revisiting the dipeptidyl carboxypeptidase inhibitor captopril as a source of pan anti-trypanosomatid agents

AU - Garsi, Jean Baptiste

AU - Hocine, Sofiane

AU - Hensienne, Raphaël

AU - Moitessier, Matthieu

AU - Denton, Helen

AU - Major, Louise L.

AU - Smith, Terry K.

AU - Hanessian, Stephen

N1 - Funding: The TKS group thanks the Medical Research Council (MR/Mo20118/1) and University of St Andrews for financial support.

PY - 2024/9/15

Y1 - 2024/9/15

N2 - 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.

AB - 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.

KW - Antiprotozoal

KW - Captopril surrogates

KW - Proline amides

KW - ‘Big eye’ phenotype

U2 - 10.1016/j.bmcl.2024.129883

DO - 10.1016/j.bmcl.2024.129883

M3 - Article

AN - SCOPUS:85198755459

SN - 0960-894X

VL - 110

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

M1 - 129883

ER -

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

Abstract

Keywords

UN SDGs

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