Cytotoxicity andIn VitroAntileishmanial Activity of Antimony (V), Bismuth (V), and Tin (IV) Complexes of Lapachol

Marcele Neves Rocha,Meiriane Mariano Da Silva,Paula Monalisa Nogueira,Ludmila Gonçalvez De Oliveira,Frédéric Frézard,Maria Norma Melo,Cynthia Demicheli,Rodrigo Pedro Soares

doi:10.1155/2013/961783

Marcele Neves Rocha, Meiriane Mariano Da Silva + Show 6 more

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https://doi.org/10.1155/2013/961783

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Abstract

Leishmania amazonensis is the etiologic agent of the cutaneous and diffuse leishmaniasis often associated with drug resistance. Lapachol [2-hydroxy-3-(3′-methyl-2-butenyl)-1,4-naphthoquinone] displays a wide range of antimicrobial properties against many pathogens. In this study, using the classic microscopic in vitro model, we have analyzed the effects of a series of lapachol and chlorides complexes with antimony (V), bismuth (V), and tin (IV) against L. amazonensis. All seven compounds exhibited antileishmanial activity, but most of the antimony (V) and bismuth (V) complexes were toxic against human HepG2 cells and murine macrophages. The best IC50 values (0.17 ± 0.03 and 0.10 ± 0.11 μg/mL) were observed for Tin (IV) complexes (3) [(Lp)(Ph3Sn)] and (6) (Ph3SnCl2), respectively. Their selective indexes (SIs) were 70.65 and 120.35 for HepG2 cells, respectively. However, while analyzing murine macrophages, the SI decreased. Those compounds were moderately toxic for HepG2 cells and toxic for murine macrophages, still underlying the need of chemical modification in this class of compounds.

Highlights

Leishmania amazonensis, a New World species, has been identified as a dermotropic species often associated with drug resistance [1]
The IC50 values were calculated based on the percentage of infected macrophages [15]
All compounds were toxic for murine macrophages (SI < 20)

Summary

Introduction

Leishmania amazonensis, a New World species, has been identified as a dermotropic species often associated with drug resistance [1]. Current antileishmanial therapies are toxic to human and some fail [2, 3]. The absence of a low toxic and safe oral drug still underlines the need for new antileishmanial compounds. In Leishmania, lapachol analogues, derivatives, and complexes have been tested by several groups. Isolapachol, and some of their derivatives were active in vitro and in vivo against Leishmania braziliensis and L. amazonensis, respectively [5]. Bismuth (III), antimony (V), and tin (IV) complexes were active against Helicobacter pylori, Leishmania major, and Leishmania donovani, respectively [6,7,8]

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