New alkenyl derivative from Piper malacophyllum and analogues: Antiparasitic activity against Trypanosoma cruzi and Leishmania infantum

New alkenyl derivative from Piper malacophyllum and analogues: Antiparasitic activity against Trypanosoma cruzi and Leishmania infantum

Author Varela, Marina T. Autor UNIFESP Google Scholar
Lima, Marta L. Google Scholar
Galuppo, Mariana K. Google Scholar
Tempone, Andre G. Google Scholar
de Oliveira, Alberto Google Scholar
Lago, Joao Henrique G. Google Scholar
Fernandes, Joao Paulo S. Autor UNIFESP Google Scholar
Abstract Alkylphenols isolated from Piper malacophyllum (Piperaceae), gibbilimbols A and B, showed interesting activity against the parasites Trypanosoma cruzi and Leishmania infantum. In continuation to our previous work, a new natural product from the essential oil of the leaves of P.malacophyllum was isolated, the 5-[(3E)-oct-3-en-1-il]-1,3-benzodioxole, and also a new set of five compounds was prepared. The antiparasitic activity of the natural product was evaluated in vitro against these parasites, indicating potential against the promastigote/trypomastigote/amastigote forms (IC50 32-83m) of the parasites and low toxicity (CC50>200m) to mammalian cells. The results obtained to the synthetic compounds indicated that the new derivatives maintained the promising antiparasitic activity, but the cytotoxicity was considerably lowered. The amine derivative LINS03011 displayed the most potent IC50 values (13.3 and 16.7m) against amastigotes of T.cruzi and L.infantum, respectively, indicating comparable activity to the phenolic prototype LINS03003, with threefold decreased (CC50 73.5m) cytotoxicity, leading the selectivity index (SI) towards the parasites up to 24.5. In counterpart, LINS03011 has not shown membrane disruptor activity in SYTOX Green model. In summary, this new set showed the hydroxyl is not essential for the antiparasitic activity, and its substitution could decrease the toxicity to mammalian cells.
Keywords gibbilimbol analogues
leishmanicidal
natural product derivatives
SAR
trypanocidal
xmlui.dri2xhtml.METS-1.0.item-coverage Hoboken
Language English
Sponsor Fundacao de Amparo a Pesquisa do Estado de Sao Paulo [2012/18756-1, 2013/50228-8, 2015/11936-2, 2016/00195-4]
Conselho Nacional de Desenvolvimento Cientifico e Tecnologico [455411/2014-0]
Grant number FAPESP: 2012/18756-1
FAPESP: 2013/50228-8
FAPESP: 2015/11936-2
FAPESP: 2016/00195-4
CNPq: 455411/2014-0
Date 2017
Published in Chemical Biology & Drug Design. Hoboken, v. 90, n. 5, p. 1007-1011, 2017.
ISSN 1747-0277 (Sherpa/Romeo, impact factor)
Publisher Wiley
Extent 1007-1011
Origin http://dx.doi.org/10.1111/cbdd.12986
Access rights Closed access
Type Article
Web of Science ID WOS:000414165500036
URI https://repositorio.unifesp.br/handle/11600/58269

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