Antiprotozoal activities of marine polyether triterpenoids.
Bioorg Chem
; 92: 103276, 2019 11.
Article
em En
| MEDLINE
| ID: mdl-31539745
ABSTRACT
Chagas disease and leishmaniasis are tropical neglected diseases caused by kinetoplastids protozoan parasites of Trypanosoma and Leishmania genera, and a public health burden with high morbidity and mortality rates in developing countries. Among difficulties with their epidemiological control, a major problem is their limited and toxic treatments to attend the affected populations; therefore, new therapies are needed in order to find new active molecules. In this work, sixteen Laurencia oxasqualenoid metabolites, natural compounds 1-11 and semisynthetic derivatives 12-16, were tested against Leishmania amazonensis, Leishmania donovani and Trypanosoma cruzi. The results obtained point out that eight substances possess potent activities, with IC50 values in the range of 5.40-46.45⯵M. The antikinetoplastid action mode of the main metabolite dehydrothyrsiferol (1) was developed, also supported by AFM images. The semi-synthetic active compound 28-iodosaiyacenol B (15) showed an IC50 5.40⯵M against Leishmania amazonensis, turned to be non-toxic against the murine macrophage cell line J774A.1 (CC50â¯>â¯100). These values are comparable with the reference compound miltefosine IC50 6.48⯱â¯0.24 and CC50 72.19⯱â¯3.06⯵M, suggesting that this substance could be scaffold for development of new antikinetoplastid drugs.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Triterpenos
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Trypanosoma cruzi
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Éteres
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Leishmania
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Antiprotozoários
Limite:
Animals
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article