title: The efficacy of 2-nitrovinylfuran derivatives against Leishmania in vitro and in vivo.
abstract: 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 vaginalis and 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(r) (a furvina-containing antifungal ointment) for the treatment of CL.
authors.affiliation: Centro de Bioactivos Químicos, Universidad Central Martha Abreu de Las Villas, Santa Clara, Villa Clara, Cuba.
authors.forename: Sergio
authors.initials: S
authors.lastname: Sifontes-Rodríguez
authors.affiliation: Instituto de Medicina Tropical Pedro Kourí, La Habana, Cuba.
authors.forename: Lianet
authors.initials: L
authors.lastname: Monzote-Fidalgo
authors.affiliation: Centro de Bioactivos Químicos, Universidad Central Martha Abreu de Las Villas, Santa Clara, Villa Clara, Cuba.
authors.forename: Nilo
authors.initials: N
authors.lastname: Castañedo-Cancio
authors.affiliation: Instituto de Medicina Tropical Pedro Kourí, La Habana, Cuba.
authors.forename: Ana Margarita
authors.initials: AM
authors.lastname: Montalvo-Álvarez
authors.affiliation: Centro de Biociencias, Universidad Autónoma de San Luis Potosí, San Luis Potosí, SLP, México.
authors.forename: Yamilé
authors.initials: Y
authors.lastname: López-Hernández
authors.affiliation: Centro de Bioactivos Químicos, Universidad Central Martha Abreu de Las Villas, Santa Clara, Villa Clara, Cuba.
authors.forename: Niurka Mollineda
authors.initials: NM
authors.lastname: Diogo
authors.affiliation: Instituto Finlay, La Habana, Cuba.
authors.forename: Juan Francisco
authors.initials: JF
authors.lastname: Infante-Bourzac
authors.affiliation: Instituto Finlay, La Habana, Cuba.
authors.forename: Oliver
authors.initials: O
authors.lastname: Pérez-Martín
authors.affiliation: Centro de Bioactivos Químicos, Universidad Central Martha Abreu de Las Villas, Santa Clara, Villa Clara, Cuba.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Meneses-Marcel
authors.affiliation: Departamento de Parasitología, Facultad de Farmacia, Universidad Complutense de Madrid, Madrid, España.
authors.forename: José Antonio Escario
authors.initials: JA
authors.lastname: García-Trevijano
authors.affiliation: Centro de Bioactivos Químicos, Universidad Central Martha Abreu de Las Villas, Santa Clara, Villa Clara, Cuba.
authors.forename: Miguel Ángel
authors.initials: MÁ
authors.lastname: Cabrera-Pérez
mesh_terms: D000666:Amphotericin B / Q000008:administration & dosage; D000818:Animals; D000981:Antiprotozoal Agents / Q000008:administration & dosage*; D049109:Cell Proliferation / Q000187:drug effects*; D002986:Clinical Trials as Topic; D004195:Disease Models, Animal; D005260:Female; D005663:Furans / Q000008:administration & dosage*; D006801:Humans; D066298:In Vitro Techniques; D020128:Inhibitory Concentration 50; D007624:KB Cells / Q000187:drug effects; D007891:Leishmania / Q000145:classification / Q000187:drug effects* / Q000254:growth & development; D016773:Leishmaniasis, Cutaneous / Q000188:drug therapy*; D008807:Mice, Inbred BALB C; D058069:Neglected Diseases / Q000188:drug therapy; D013997:Time Factors; D014753:Vinyl Compounds / Q000008:administration & dosage
chemical_list: C577632:2-bromo-5-(2-bromo-2-nitrovinyl)furan; D000981:Antiprotozoal Agents; D005663:Furans; C490023:UC245; D014753:Vinyl Compounds; C027684:2-vinylfuran; D000666:Amphotericin B