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

• Published in: Memórias do Instituto Oswaldo Cruz Vol. 110; no. 2; pp. 166 - 173
• Main Authors: Sifontes-Rodríguez, Sergio, Monzote-Fidalgo, Lianet, Castañedo-Cancio, Nilo, Montalvo-Álvarez, Ana Margarita, López-Hernández, Yamilé, Diogo, Niurka Mollineda, Infante-Bourzac, Juan Francisco, Pérez-Martín, Oliver, Meneses-Marcel, Alfredo, García-Trevijano, José Antonio Escario, Cabrera-Pérez, Miguel Ángel
• Format: Journal Article
• Language: English
• Published: Brazil Fundação Oswaldo Cruz, Fiocruz 01-04-2015; Instituto Oswaldo Cruz, Ministério da Saúde; Fundação Oswaldo Cruz (FIOCRUZ)
• Subjects: Amphotericin B - administration & dosage; Animals; Antiprotozoal Agents - administration & dosage; BALB/c; Cell Proliferation - drug effects; Clinical Trials as Topic; Disease Models, Animal; Female; Furans - administration & dosage; furvina; Humans; In Vitro Techniques; Inhibitory Concentration 50; KB Cells - drug effects; Leishmania; Leishmania - classification; Leishmania - drug effects; Leishmania - growth & development; Leishmaniasis, Cutaneous - drug therapy; Mice, Inbred BALB C; Neglected Diseases - drug therapy; nitrovinylfuran; promastigote; Time Factors; UC245; Vinyl Compounds - administration & dosage
• ISSN: 1678-8060; 0074-0276; 1678-8060
• DOI: 10.1590/0074-02760140324

Despite recent advances in the treatment of some forms of
leishmaniasis, the available drugs are still far from ideal due to
inefficacy, parasite resistance, toxicity and cost. The wide-spectrum
antimicrobial activity of 2-nitrovinylfuran compounds has been
described, as has their activity against Trichomonas vaginalisand other
protozoa. Thus, the aim of this study was to test the antileishmanial
activities 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 of Leishmania amazonensis, Leishmania infantum and
Leishmania braziliensis were determined, as were the efficacies of two
selected compounds in an experimental model of cutaneous leishmaniasis
(CL) caused by L. amazonensis in BALB/c mice. All of the compounds were
active against the promastigotes of the three Leishmania species
tested. IC50 and MPC values were in the ranges of 0.8-4.7 μM and
1.7-32 μM, respectively. The compounds
2-bromo-5-(2-bromo-2-nitrovinyl)-furan (furvina) and
2-bromo-5-(2-methyl-2-nitrovinyl)-furan (UC245) also reduced lesion
growth in vivo at a magnitude comparable to or higher than that
achieved by amphotericin B treatment. The results demonstrate the
potential of this class of compounds as antileishmanial agents and
support the clinical testing of Dermofural® (a furvina-containing
antifungal ointment) for the treatment of CL.