title: Leishmanicidal constituents from the leaves of Piper rusbyi.
abstract: The kavapyrone (+)-(7 R,8 S)-epoxy-5,6-didehydrokavain (1) and the chalcone flavokavain B (2) were isolated from Piper rusbyi as the bioactive components by bioassay-guided fractionation, using an in vitro assay against promastigote forms of three Leishmania strains. In addition, the new kavapyrone, (7 R,8 R/7 S,8 S)-dihydroxy-5,6-didehydrokavain (3), which is very likely an artifact, and four known compounds (4-7) were isolated. Their structures were elucidated on the basis of spectral analysis, and the absolute configurations of compounds 1 and 3 were established by CD studies and the modified Mosher ester procedure, respectively. All compounds were evaluated for in vitro leishmanicidal activity. The most active compounds 1 (IC50=81.9 microM) and 2 (IC50=11.2 microM) were also evaluated in vivo against a New World strain of cutaneous leishmaniasis, and the results showed the efficacy of 2 at a dose of 5 mg/kg/day. Compounds 1 and 3 were also assayed as reversal agents against a multidrug-resistant Leishmania tropica line, but were found to be inactive.
authors.affiliation: Instituto Universitario de Bio-Orgánica Antonio González, Universidad de La Laguna, Tenerife, Canary Islands, Spain.
authors.forename: Ninoska
authors.initials: N
authors.lastname: Flores
authors.forename: Gabriela
authors.initials: G
authors.lastname: Cabrera
authors.forename: Ignacio A
authors.initials: IA
authors.lastname: Jiménez
authors.forename: Jose
authors.initials: J
authors.lastname: Piñero
authors.forename: Alberto
authors.initials: A
authors.lastname: Giménez
authors.forename: Genevieve
authors.initials: G
authors.lastname: Bourdy
authors.forename: Fernando
authors.initials: F
authors.lastname: Cortés-Selva
authors.forename: Isabel L
authors.initials: IL
authors.lastname: Bazzocchi
mesh_terms: D000818:Animals; D000981:Antiprotozoal Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D007891:Leishmania / Q000145:classification / Q000187:drug effects*; D007896:Leishmaniasis / Q000188:drug therapy; D021261:Parasitic Sensitivity Tests; D008517:Phytotherapy; D031701:Piper; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D018515:Plant Leaves
chemical_list: D000981:Antiprotozoal Agents; D010936:Plant Extracts