%0 Journal Article
%T Cytotoxicity and In Vitro Antileishmanial Activity of Antimony (V), Bismuth (V), and Tin (IV) Complexes of Lapachol
%A Marcele Neves Rocha
%A Paula Monalisa Nogueira
%A Cynthia Demicheli
%A Ludmila Gon£¿alvez de Oliveira
%A Meiriane Mariano da Silva
%A Fr¨¦d¨¦ric Fr¨¦zard
%A Maria Norma Melo
%A Rodrigo Pedro Soares
%J Bioinorganic Chemistry and Applications
%D 2013
%I Hindawi Publishing Corporation
%R 10.1155/2013/961783
%X Leishmania amazonensis is the etiologic agent of the cutaneous and diffuse leishmaniasis often associated with drug resistance. Lapachol [2-hydroxy-3-(3¡ä-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£¿ g/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. 1. 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 simply fail [2, 3]. In the Americas, for over six decades, parenteral administrations of pentavalent antimonials (Sb-V), sodium stibogluconate (Pentostam), and meglumine antimoniate (Glucantime) have been used for treating leishmaniasis. In places where resistance to antimonials is common, such as India, other chemotherapeutic treatments include amphotericin B and pentamidine [2, 4]. Therefore, the absence of a low toxic and safe oral drug still underlines the need for new antileishmanial compounds. Lapachol,£¿[2-hydroxy-3-(3¡ä-methyl-2-butenyl)-1,4-naphthoquinone] (Figure 1) is a natural compound extracted from the core of Bignoniaceae trees. In Leishmania, lapachol analogues, derivatives, and complexes have been tested by several groups. Lapachol, 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¨C8]. Figure 1: Structures of lapachol metal (Bi, Sb, and Sn) complexes ( 1¨C 3) and chloride metal (Bi, Sb, and Sn) compounds ( 4¨C 6) and lapachol ( 7). Legend: Bi = bismuth, Sb = antimony, and Sn = tin. The design of bifunctional
%U http://www.hindawi.com/journals/bca/2013/961783/