Navegando por Palavras-chave "Gibbilimbol B"

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    Gibbilimbol analogues as antiparasitic agents-Synthesis and biological activity against Trypanosoma cruzi and Leishmania (L.) infantum
    (Pergamon-Elsevier Science Ltd, 2016) Varela, Marina T. [UNIFESP]; Dias, Roberto Z. [UNIFESP]; Martins, Ligia F.; Ferreira, Daiane D.; Tempone, Andre G.; Ueno, Anderson K. [UNIFESP]; Lago, Joao Henrique G. [UNIFESP]; Fernandes, Joao Paulo S. [UNIFESP]
    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.
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    Leishmanicidal activity of an alkenylphenol from Piper malacophyllum is related to plasma membrane disruption
    (Elsevier B.V., 2012-11-01) Oliveira, Alberto de; Mesquita, Juliana T.; Tempone, Andre G.; Lago, Joao Henrique Ghilardi [UNIFESP]; Guimaraes, Elsie F.; Kato, Massuo J.; Universidade Federal de Uberlândia (UFU); Adolfo Lutz Inst; Universidade Federal de São Paulo (UNIFESP); Inst Pesquisas Jardim Bot Rio de Janeiro; Universidade de São Paulo (USP)
    Leishmaniasis and Chagas disease are parasitic protozoan infections that affect the poorest population in the world, causing high mortality and morbidity. As a result of highly toxic and long-duration treatments, novel, safe and more efficacious drugs are essential. in this work, the methanol (MeOH) extract from the leaves of Piper malacophyllum (Piperaceae) was fractioned to afford one alkenylphenol, which was characterized as 4-[(3'E)-decenyl]phenol (gibbilimbol B) by spectroscopic methods. Anti-protozoan in vitro assays demonstrated for the first time that Leishmania (L.) infantum chagasi was susceptible to gibbilimbol B. with an in vitro EC50 of 23 mu g/mL against axenic promastigotes and an EC50 of 22 mu g/mL against intracellular amastigotes. Gibbilimbol B was also tested for anti-trypanosomal activity (Trypanosoma cruzi) and showed an EC50 value of 17 mu g/mL against trypomastigotes. To evaluate the cytotoxic parameters, this alkenylphenol was tested in vitro against NCTC cells, showing a CC50 of 59 mu g/mL and absent hemolytic activity at the highest concentration of 75 mu g/mL. Using the fluorescent probe SYTOX Green suggested that the alkenylphenol disrupted the Leishmania plasma membrane upon initial incubation. Further drug design studies aiming at derivatives could be a promising tool for the development of new therapeutic agents for leishmaniasis and Chagas disease. (C) 2012 Elsevier Inc. All rights reserved.