The efficacy of 2-nitrovinylfuran derivatives against Leishmania in vitro and in vivo

Despite recent advances in the treatment of some forms of leishmaniasis, theavailable drugs are still far from ideal due to inefficacy, parasite resistance,toxicity and cost. The wide-spectrum antimicrobial activity of 2-nitrovinylfurancompounds has been described, as has their activity against Trichomonas vaginalis andother protozoa. Thus, the aim of this study was to test the antileishmanialactivities of six 2-nitrovinylfurans in vitro and in a murine model of leishmaniasis.Minimum parasiticide concentration (MPC) and 50% inhibitory concentration(IC₅₀) values for these compounds against the promastigotes ofLeishmania amazonensis, Leishmania infantum and Leishmania braziliensis weredetermined, as were the efficacies of two selected compounds in an experimental modelof cutaneous leishmaniasis (CL) caused by L. amazonensis in BALB/c mice. All of thecompounds were active against the promastigotes of the three Leishmania speciestested. IC₅₀ and MPC values were in the ranges of 0.8-4.7 µM and 1.7-32µM, respectively. The compounds 2-bromo-5-(2-bromo-2-nitrovinyl)-furan (furvina) and2-bromo-5-(2-methyl-2-nitrovinyl)-furan (UC245) also reduced lesion growth in vivo ata magnitude comparable to or higher than that achieved by amphotericin B treatment.The results demonstrate the potential of this class of compounds as antileishmanialagents and support the clinical testing of Dermofural^(r) (afurvina-containing antifungal ointment) for the treatment of CL.