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An unprecedented chlorine-containing piperamide from Piper pseudoarboreum as potential leishmanicidal agent
Ninoska Flores1, Juan C Ticona1, Pablo Bilbao-Ramos2
1Instituto Universitario de Bio-Orgánica Antonio González, Departamento de Química Orgánica, Universidad de La Laguna, Avenida Astrofísico Francisco Sánchez 2, 38206 La Laguna, Tenerife, Spain; Instituto de Investigaciones Fármaco Bioquímicas, Facultad de Ciencias Farmacéuticas y Bioquímicas, Universidad Mayor de San Andrés, Avda. Saavedra 2224, Miraflores, La Paz, Bolivia.
Abstract:
A phytochemical investigation of the ethanolic extract of leaves from Piper pseudoarboreum led to the isolation of 3-chlorosintenpyridone 1, an unprecedented chlorinated piperamide, together with the known compounds 2-12. Their structures were established based on 1D and 2D (COSY, ROESY, HMQC, and HMBC) NMR spectroscopy, in addition to high resolution mass spectrometry. The proposed biosynthetic pathway of compound 1 is discussed. Compounds 1-12 were tested in vitro for their leishmanicidal potential against promastigote stages of Leishmania amazonensis, L braziliensis, L. guyanensis and L. infantum. Two compounds from this series, the alkamide 1 (IC50 3.4-5.2 μM) and the fatty acid 9 (IC50 18.7-29.6 μM) displayed higher or similar potency to Miltefosine, used as the reference drug.
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