Abstract
The kavapyrone (+)-(7R ,8S )-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, (7R ,8R /7S ,8S )-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 μM) and 2 (IC50 = 11.2 μM) 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.
Key words
Piperaceae -
Piper rusbyi
- kavapyrones - chalcones -
Leishmania
- reversal of multidrug-resistance activities
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Isabel López Bazzocchi
Instituto Universitario de Bio-Orgánica ”Antonio González”
Universidad de La Laguna
Avenida Astrofísico Francisco Sánchez 2
La Laguna
38206 Tenerife
Canary Islands
Spain
Phone: +34-922-318-594
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Email: ilopez@ull.es