title: In vitro and in vivo Leishmanicidal activity of 2-hydroxy-3-(3-methyl-2-butenyl)-1,4-naphthoquinone (lapachol).
abstract: 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(R)). 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(R) 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.
authors.affiliation: Núcleo de Medicina Tropical Prof. Joaquim Eduardo de Alencar, Faculdade de Medicina, Universidade Federal do Ceará, Rua Alexandre Baraúna, 949, 60.430-160 Fortaleza, CE, Brazil. pato@ufc.br
authors.forename: M J
authors.initials: MJ
authors.lastname: Teixeira
authors.forename: Y M
authors.initials: YM
authors.lastname: de Almeida
authors.forename: J R
authors.initials: JR
authors.lastname: Viana
authors.forename: J G
authors.initials: JG
authors.lastname: Holanda Filha
authors.forename: T P
authors.initials: TP
authors.lastname: Rodrigues
authors.forename: J R
authors.initials: JR
authors.lastname: Prata
authors.forename: I C
authors.initials: IC
authors.lastname: Coêlho
authors.forename: V S
authors.initials: VS
authors.lastname: Rao
authors.forename: M M
authors.initials: MM
authors.lastname: Pompeu
mesh_terms: D000818:Animals; D000967:Antimony Sodium Gluconate / Q000627:therapeutic use; D000981:Antiprotozoal Agents / Q000494:pharmacology* / Q000627:therapeutic use; D006224:Cricetinae; D004195:Disease Models, Animal; D005260:Female; D007892:Leishmania braziliensis / Q000187:drug effects*; D016773:Leishmaniasis, Cutaneous / Q000188:drug therapy*; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000469:parasitology; D008297:Male; D008647:Mesocricetus; D051379:Mice; D009285:Naphthoquinones / Q000494:pharmacology* / Q000627:therapeutic use; D010946:Plants, Medicinal
chemical_list: D000981:Antiprotozoal Agents; D009285:Naphthoquinones; C008252:lapachol; D000967:Antimony Sodium Gluconate