Ten chalcones were synthesized and tested as potential leishmanicidal and trypanocidal agents. All tested compounds caused concentration-dependent inhibition of the in vitro growth of Leishmania braziliensis and Trypanosoma cruzi with no significant toxic effect towards host macrophages. Our results show that the positions of the substituents seem to be critical for their antiprotozoal activities.Among the kinetoplastid protozoa, which infect invertebrates, mammals, and plants, some species are of particular interest due to their medical importance. These include Trypanosoma cruzi (the agent of Chagas' disease), the African trypanosome responsible for sleeping sickness, and several species of Leishmania, which cause the various forms of leishmaniasis (9). The World Health Organization has identified Chagas' disease and leishmaniasis as major and increasing public health problems, particularly in Latin America (14,15,16,18). In spite of the socioeconomic importance of these tropical infectious diseases, efforts directed towards the discovery of new drugs and/or vaccines against them are underdeveloped (10, 13). In addition, most of the drugs currently in use (i) were developed several decades ago, (ii) show variable efficacy, (iii) have serious side effects, (iv) are expensive, (v) can require long-term treatment, (vi) may have low activity in immunosuppressed patients, and (vii) present and/or induce resistance in parasites (9, 10, 16). Thus, the need for the development of new, effective, cheap, and safe drugs for the treatment of leishmaniasis and Chagas' disease is very important.Chalcones, or 1,3-diaryl-2-propen-1-ones, are natural or synthetic compounds belonging to the flavonoid family. Chalcones possess a broad spectrum of biological activities, including antibacterial, anthelmintic, amoebicidal, antiulcer, antiviral, insecticidal, antiprotozoal, anticancer, cytotoxic, and immunosuppressive activities (for reviews, see references 11 and 12). The present study was designed to determine the in vitro leishmanicidal and trypanocidal activities of the 10 substitutioncontaining chalcones and to investigate the cytotoxic effects of these chalcones on mouse peritoneal macrophages in vitro.The chalcones used in the present study were synthesized in our laboratory by reaction of the appropriate aryl methyl ketone and aryl aldehyde (in a 1:1 ratio) in the presence of sodium hydroxide and ethanol. The products were then added to cooled diluted acetic acid according to the methodology previously described (8). The synthetic reaction gave substantial yields (55 to 98%) of all the chalcones, and these were characterized by 1 H nuclear magnetic resonance and infrared analyses and by microanalysis. The substitution-containing chalcones were dissolved in 0.5% Tween 80 in phosphatebuffered saline to prepare a working solution with a 0.1 M concentration before being passed through 0.22-m-pore-size Millipore filters. The structures of the chalcones are shown in Table 1.Cultures of promastigote forms of Leishmania braziliensis...

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Intracellular multiplication of Trypanosoma rangeli was evaluated in vitro using experimental infection of Vero cells, murine macrophages, and promonocytes with T. rangeli Choachi, Macias, and SC-58 clone B1 strains. Our results revealed a low infectivity of all T. rangeli strains to these cell lines. Macrophages showed the highest infection rate; however, intracellular forms were no longer observed 48 h post infection Despite the observation of intracellular parasites up to 144 h post infection, the infection rates of Vero cells and J774G.8 promonocytes with these parasite strains were always below 5%. Pre-incubation of parasites with normal mouse serum increased the initial infectivity but not the time course of the infection. Under our experimental conditions, we did not observe any evidence of intracellular multiplication of T. rangeli within these cell lines.