Leishmania amazonensis response to artemisinin and derivatives.
Parasitol Int
; 80: 102218, 2021 Feb.
Article
em En
| MEDLINE
| ID: mdl-33137506
The worldwide presence of Leishmania parasites increases in the poorest regions. Current leishmaniasis treatments are unsatisfactory due to resistance development, side effects and cost. Herein, we describe the in vitro activity of artemisinin (ART), artemether (ATM), artesunate (ATS) and dihydroartemisinin (DHA) against Leishmania amazonensis. Selected compounds were assayed in the animal model of cutaneous leishmaniasis in BALB/c mice. On intracellular amastigotes, similar activity (pâ¯>â¯0.05) was observed for ART, ATM and ATS (IC50â¯=â¯15.0-19.2⯵M), which were inferior (pâ¯<â¯0.05) respect to reference endoperoxide ascaridole (IC50â¯=â¯11.5⯱â¯1.0⯵M) and superior (pâ¯<â¯0.05) compared with reference drug Glucantime® (IC50â¯=â¯30.1⯱â¯9.0⯵M). In contrast, DHA (IC50â¯=â¯38.5⯱â¯4.7⯵M) showed higher IC50 values (pâ¯<â¯0.05) than other artemisinins and ascaridole, but similar (pâ¯>â¯0.05) than Glucantime®; while deoxyartemisinin caused smaller inhibition (IC50â¯=â¯88.9⯱â¯5.2⯵M). Selectivity indexes of >13, 6, 11 and 1 were obtained for ART, ATM, ATS and DHA, respectively. In addition, the potential effect of ART and ATS was also demonstrated in the murine model, causing a significant reduction (pâ¯<â¯0.05) of the lesion size and parasite load regarding untreated animals and treated with vehicle. Effects of both artemisinins were comparable (pâ¯>â¯0.05) with Glucantime® and ascaridole-treated mice. In particular, artemisinin is recommended to further studies, which could be an advantage over the ascaridole endoperoxide and could be useful in endemic areas of parasite resistance to antimonials.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Tripanossomicidas
/
Leishmania mexicana
/
Artemisininas
/
Carga Parasitária
Limite:
Animals
Idioma:
En
Revista:
Parasitol Int
Assunto da revista:
PARASITOLOGIA
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Cuba
País de publicação:
Holanda