Strasseriolides display in vitro and in vivo activity against trypanosomal parasites and cause morphological and size defects in Trypanosoma cruzi.
Neglected diseases caused by kinetoplastid parasites are a health burden in tropical and subtropical countries. The need to create safe and effective medicines to improve treatment remains a priority. Microbial natural products are a source of chemical diversity that provides a valuable approach for...
Published in: | PLOS Neglected Tropical Diseases |
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Online Access: | https://doi.org/10.1371/journal.pntd.0011592 https://doaj.org/article/ffcbe13d16da4812b2ad142c71b0f764 |
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ftdoajarticles:oai:doaj.org/article:ffcbe13d16da4812b2ad142c71b0f764 2023-11-12T04:13:46+01:00 Strasseriolides display in vitro and in vivo activity against trypanosomal parasites and cause morphological and size defects in Trypanosoma cruzi. Cristina Bosch-Navarrete Guiomar Pérez-Moreno Frederick Annang Rosario Diaz-Gonzalez Raquel García-Hernández Hedy Rocha Francisco Gamarro Carlos Cordón-Obras Miguel Navarro Ana Rodriguez Olga Genilloud Fernando Reyes Francisca Vicente Luis M Ruiz-Pérez Dolores González-Pacanowska 2023-09-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0011592 https://doaj.org/article/ffcbe13d16da4812b2ad142c71b0f764 EN eng Public Library of Science (PLoS) https://journals.plos.org/plosntds/article/file?id=10.1371/journal.pntd.0011592&type=printable https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0011592 https://doaj.org/article/ffcbe13d16da4812b2ad142c71b0f764 PLoS Neglected Tropical Diseases, Vol 17, Iss 9, p e0011592 (2023) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2023 ftdoajarticles https://doi.org/10.1371/journal.pntd.0011592 2023-10-29T00:38:43Z Neglected diseases caused by kinetoplastid parasites are a health burden in tropical and subtropical countries. The need to create safe and effective medicines to improve treatment remains a priority. Microbial natural products are a source of chemical diversity that provides a valuable approach for identifying new drug candidates. We recently reported the discovery and bioassay-guided isolation of a novel family of macrolides with antiplasmodial activity. The novel family of four potent antimalarial macrolides, strasseriolides A-D, was isolated from cultures of Strasseria geniculata CF-247251, a fungal strain obtained from plant tissues. In the present study, we analyze these strasseriolides for activity against kinetoplastid protozoan parasites, namely, Trypanosoma brucei brucei, Leishmania donovani and Trypanosoma cruzi. Compounds exhibited mostly low activities against T. b. brucei, yet notable growth inhibition and selectivity were observed for strasseriolides C and D in the clinically relevant intracellular T. cruzi and L. donovani amastigotes with EC50 values in the low micromolar range. Compound C is fast-acting and active against both intracellular and trypomastigote forms of T. cruzi. While cell cycle defects were not identified, prominent morphological changes were visualized by differential interference contrast microscopy and smaller and rounded parasites were visualized upon exposure to strasseriolide C. Moreover, compound C lowers parasitaemia in vivo in acute models of infection of Chagas disease. Hence, strasseriolide C is a novel natural product active against different forms of T. cruzi in vitro and in vivo. The study provides an avenue for blocking infection of new cells, a strategy that could additionally contribute to avoid treatment failure. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLOS Neglected Tropical Diseases 17 9 e0011592 |
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Directory of Open Access Journals: DOAJ Articles |
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ftdoajarticles |
language |
English |
topic |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
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Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Cristina Bosch-Navarrete Guiomar Pérez-Moreno Frederick Annang Rosario Diaz-Gonzalez Raquel García-Hernández Hedy Rocha Francisco Gamarro Carlos Cordón-Obras Miguel Navarro Ana Rodriguez Olga Genilloud Fernando Reyes Francisca Vicente Luis M Ruiz-Pérez Dolores González-Pacanowska Strasseriolides display in vitro and in vivo activity against trypanosomal parasites and cause morphological and size defects in Trypanosoma cruzi. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
Neglected diseases caused by kinetoplastid parasites are a health burden in tropical and subtropical countries. The need to create safe and effective medicines to improve treatment remains a priority. Microbial natural products are a source of chemical diversity that provides a valuable approach for identifying new drug candidates. We recently reported the discovery and bioassay-guided isolation of a novel family of macrolides with antiplasmodial activity. The novel family of four potent antimalarial macrolides, strasseriolides A-D, was isolated from cultures of Strasseria geniculata CF-247251, a fungal strain obtained from plant tissues. In the present study, we analyze these strasseriolides for activity against kinetoplastid protozoan parasites, namely, Trypanosoma brucei brucei, Leishmania donovani and Trypanosoma cruzi. Compounds exhibited mostly low activities against T. b. brucei, yet notable growth inhibition and selectivity were observed for strasseriolides C and D in the clinically relevant intracellular T. cruzi and L. donovani amastigotes with EC50 values in the low micromolar range. Compound C is fast-acting and active against both intracellular and trypomastigote forms of T. cruzi. While cell cycle defects were not identified, prominent morphological changes were visualized by differential interference contrast microscopy and smaller and rounded parasites were visualized upon exposure to strasseriolide C. Moreover, compound C lowers parasitaemia in vivo in acute models of infection of Chagas disease. Hence, strasseriolide C is a novel natural product active against different forms of T. cruzi in vitro and in vivo. The study provides an avenue for blocking infection of new cells, a strategy that could additionally contribute to avoid treatment failure. |
format |
Article in Journal/Newspaper |
author |
Cristina Bosch-Navarrete Guiomar Pérez-Moreno Frederick Annang Rosario Diaz-Gonzalez Raquel García-Hernández Hedy Rocha Francisco Gamarro Carlos Cordón-Obras Miguel Navarro Ana Rodriguez Olga Genilloud Fernando Reyes Francisca Vicente Luis M Ruiz-Pérez Dolores González-Pacanowska |
author_facet |
Cristina Bosch-Navarrete Guiomar Pérez-Moreno Frederick Annang Rosario Diaz-Gonzalez Raquel García-Hernández Hedy Rocha Francisco Gamarro Carlos Cordón-Obras Miguel Navarro Ana Rodriguez Olga Genilloud Fernando Reyes Francisca Vicente Luis M Ruiz-Pérez Dolores González-Pacanowska |
author_sort |
Cristina Bosch-Navarrete |
title |
Strasseriolides display in vitro and in vivo activity against trypanosomal parasites and cause morphological and size defects in Trypanosoma cruzi. |
title_short |
Strasseriolides display in vitro and in vivo activity against trypanosomal parasites and cause morphological and size defects in Trypanosoma cruzi. |
title_full |
Strasseriolides display in vitro and in vivo activity against trypanosomal parasites and cause morphological and size defects in Trypanosoma cruzi. |
title_fullStr |
Strasseriolides display in vitro and in vivo activity against trypanosomal parasites and cause morphological and size defects in Trypanosoma cruzi. |
title_full_unstemmed |
Strasseriolides display in vitro and in vivo activity against trypanosomal parasites and cause morphological and size defects in Trypanosoma cruzi. |
title_sort |
strasseriolides display in vitro and in vivo activity against trypanosomal parasites and cause morphological and size defects in trypanosoma cruzi. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2023 |
url |
https://doi.org/10.1371/journal.pntd.0011592 https://doaj.org/article/ffcbe13d16da4812b2ad142c71b0f764 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 17, Iss 9, p e0011592 (2023) |
op_relation |
https://journals.plos.org/plosntds/article/file?id=10.1371/journal.pntd.0011592&type=printable https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0011592 https://doaj.org/article/ffcbe13d16da4812b2ad142c71b0f764 |
op_doi |
https://doi.org/10.1371/journal.pntd.0011592 |
container_title |
PLOS Neglected Tropical Diseases |
container_volume |
17 |
container_issue |
9 |
container_start_page |
e0011592 |
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