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In vitro and in vivo Leishmanicidal activity of 2‐hydroxy‐3‐(3‐methyl‐2‐butenyl)‐1,4‐naphthoquinone (lapachol)
Author(s) -
Teixeira Maria Jania,
de Almeida Yacy M.,
Viana Joseval R.,
Holanda Filha Joana G.,
Rodrigues Tatiana P.,
Prata José Rômulo C.,
Coêlho Ivo Castelo B.,
Rao Vietla S.,
Pompeu Margarida M. L.
Publication year - 2001
Publication title -
phytotherapy research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.019
H-Index - 129
eISSN - 1099-1573
pISSN - 0951-418X
DOI - 10.1002/1099-1573(200102)15:1<44::aid-ptr685>3.0.co;2-1
Subject(s) - in vivo , amastigote , in vitro , pharmacology , naphthoquinone , hamster , leishmania , leishmaniasis , mesocricetus , chemistry , biology , biochemistry , immunology , microbiology and biotechnology , botany , parasite hosting , world wide web , computer science
This study aims to evaluate the in vitro and in vivo leishmanicidal activity of lapachol, a naphthoquinone found in the seeds and heartwood of certain tropical plants, and to compare its efficacy with a reference drug, sodium stibogluconate (Pentostam®). These compounds (0.0125–4.0 mg/mL) were evaluated in vitro against intracellular amastigotes of Leishmania (Viannia) braziliensis ( LVb ), then tested in an animal model (hamster) to try to reproduce the leishmanicidal activity. In vitro , lapachol exhibited an anti‐amastigote effect, whereas in vivo it did not prevent the development of LVb ‐induced lesions at an oral dose of 300 mg/kg/day for 42 days. Pentostam® demonstrated a significant anti‐amastigote effect in vitro for LVb and apparent clinical cure in vivo (60 mg/kg/day). However, it could not completely eradicate parasites from the tissues of infected animals. The observation that lapachol exerts leishmanicidal activity in vitro without offering significant protection against LVb ‐infected lesions in hamsters suggests that lapachol in vivo might possibly inhibit the microbicidal functioning of macrophages. Alternatively, it might be transformed into an inactive metabolite(s) or neutralized, losing its leishmanicidal activity. It is also possible that an optimal and sustained plasma level of the drug could not be achieved at the dose used in this study. Copyright © 2001 John Wiley & Sons, Ltd.