Gibbilimbol analogues as antiparasitic agents-Synthesis and biological activity against Trypanosoma cruzi and Leishmania (L.) infantum

Gibbilimbol analogues as antiparasitic agents-Synthesis and biological activity against Trypanosoma cruzi and Leishmania (L.) infantum

Author Varela, Marina T. Autor UNIFESP Google Scholar
Dias, Roberto Z. Autor UNIFESP Google Scholar
Martins, Ligia F. Google Scholar
Ferreira, Daiane D. Google Scholar
Tempone, Andre G. Google Scholar
Ueno, Anderson K. Autor UNIFESP Google Scholar
Lago, Joao Henrique G. Autor UNIFESP Google Scholar
Fernandes, Joao Paulo S. Autor UNIFESP Google Scholar
Abstract The essential oils from leaves of Piper malacophyllum (Piperaceae) showed to be mainly composed by two alkenylphenol derivatives: gibbilimbols A and B. After isolation and structural characterization by NMR and MS data analysis, both compounds were evaluated against promastigote/amastigote forms of Leishmania (L.) infantum as well as trypomastigote/amastigote forms of Trypanosoma cruzi. The obtained results indicated that gibbilimbol B displayed potential against the tested parasites and low toxicity to mammalian cells, stimulating the preparation of several quite simple synthetic analogues in order to improve its activity and to explore the preliminary structure-activity relationships (SAR) data. Among the prepared derivatives, compound LINS03003 (n-octyl-4-hydroxybenzylamine) displayed the most potent IC50 values of 5.5 and 1.8 mu M against amastigotes of T. cruzi and L. (L.) infantum, respectively, indicating higher activity than the natural prototype. In addition, this compound showed remarkable selectivity index (SI) towards the intracellular forms of Leishmania (SI = 13.1) and T. cruzi (SI = 4.3). Therefore, this work indicated that preparation of synthetic compounds structurally based in the bioactive natural products could be an interesting source of novel and selective compounds against these protozoan parasites. (C) 2016 Elsevier Ltd. All rights reserved.
Keywords Gibbilimbol A
Gibbilimbol B
Natural product derivatives
xmlui.dri2xhtml.METS-1.0.item-coverage Oxford
Language English
Sponsor CNPq
Grant number CNPq: 455411/2014-0
CNPq: 470853/2012-3
CNPq: 471458/2012-0
FAPESP: 2015/11936-2
FAPESP: 2013/20479-9
FAPESP: 2012/18756-1
FAPESP: 2014/16564-3
Date 2016
Published in Bioorganic & Medicinal Chemistry Letters. Oxford, v. 26, n. 4, p. 1180-1183, 2016.
ISSN 0960-894X (Sherpa/Romeo, impact factor)
Publisher Pergamon-Elsevier Science Ltd
Extent 1180-1183
Access rights Closed access
Type Article
Web of Science ID WOS:000369377700015

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