Leishmanicidal constituents from the leaves of Piper rusbyi.
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.
Flores
Ninoska
N
Instituto Universitario de Bio-Orgánica Antonio González, Universidad de La Laguna, Tenerife, Canary Islands, Spain.
Cabrera
Gabriela
G
Jiménez
Ignacio A
IA
Piñero
Jose
J
Giménez
Alberto
A
Bourdy
Genevieve
G
Cortés-Selva
Fernando
F
Bazzocchi
Isabel L
IL
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
D000981:Antiprotozoal Agents; D010936:Plant Extracts