A Novel Organotellurium Compound (RT-01) as a New Antileishmanial Agent

Abstract

Leishmaniasis caused by the intracellular protozoan parasite of mononuclear phagocytes Leishmania is endemic in 88 countries [1]. Leishmania amazonensis, a species transmitted mainly in the Amazon region, has been associated with localized cutaneous lesions, diffuse cutaneous disease, and mucosal infection [1,2]. The disease is neglected by the pharmaceutical industry, even though no vaccine exists, and significant side effects and signs of increasing resistance continue to occur with the use of the few effective drugs available [3,4].More recently, the pharmaceutical proprieties of tellurane compounds were investigated [5,6]. Several tellurides show antioxidative and immunomodulating proprieties and antitumor activities [5][6][7][8][9][10][11][12]. Clinical trials with a tellurane compound are presently underway [13,14]. The synthetic organotellurane compound RT-01 ( Fig. 1) has been previously shown to inhibit cathepsin B, a cysteine protease involved in tumor invasion, and presents a cytotoxic effect on cancer cells [7]. In an attempt to find new leishmanial drugs, RT-01 was tested both in vitro and in vivo against L. amazonensis. The results reported here suggest that RT-01 is effective against the flagellate and nonflagellate parasitic forms and in L. amazonensis-infected BALB/c mice. MATERIALS AND METHODS Organotellurane compound (RT-01)The organotellurane RT-01 used to evaluate the effects in vitro against L. amazonensis and in vivo in L. amazonensis-infected mice was prepared by the reaction of tellurium tetrachloride with propargyl alcohol in benzene followed by complexation with triethylbenzylammonium chloride, as described previously [7,15] (Fig. 1). The compound was dissolved in DMSO and diluted in phosphate buffer pH 7.4, medium or saline. The final concentration of DMSO in vitro and in vivo experiments was 0.1%. A Novel Organotellurium Compound (RT-01) as a New Antileishmanial AgentKorean J Parasitol. Vol. 47, No. 3: 213-218, September 2009 DOI: 10.3347/kjp.2009 213 Abstract: Leishmaniasis is a neglected disease and endemic in developing countries. A lack of adequate and definitive chemotherapeutic agents to fight against this infection has led to the investigation of numerous compounds. The aim of this study was to investigate the effect of RT-01, an organotellurane compound presenting biological activities, in 2 experimental systems against Leishmania amazonensis. The in vitro system consisted of promastigotes and amastigotes forms of the parasite, and the in vivo system consisted of L. amazonensis infected BALB/c mice, an extremely susceptible mouse strain. The compound proved to be toxic against promastigotes and amastigotes. The study also showed that treatment with RT-01 produces an effect similar to that treatment with the reference antimonial drug, Glucantime, in L. amazonensis infected mice. The best results were obtained following RT-01 intralesional administration (720 μ g/kg/day); mice showed significant delay in the development of cutaneous lesions and decreased numbers of parasites ob...

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