Antiprotozoal activities of marine polyether triterpenoids.
Bioorg Chem
; 92: 103276, 2019 11.
Article
en 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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Triterpenos
/
Trypanosoma cruzi
/
Éteres
/
Leishmania
/
Antiprotozoarios
Límite:
Animals
Idioma:
En
Revista:
Bioorg Chem
Año:
2019
Tipo del documento:
Article
País de afiliación:
España