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

Autor(es)

Varela, Marina T. ^[1] ; Dias, Roberto Z. ^[1] ; Martins, Ligia F. ^[2] ; Ferreira, Daiane D. ^[2] ; Tempone, Andre G. ^[2] ; Ueno, Anderson K. ^[1] ; Lago, Joao Henrique G. ^[1] ; Fernandes, Joao Paulo S. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Fed Sao Paulo, Inst Ciencias Ambientais Quim & Farmaceut, Rua Sao Nicolau 210, BR-09913030 Diadema, SP - Brazil

^[2] Adolfo Lutz Inst, Ctr Parasitol & Micol, Ave Dr Arnaldo 355, BR-01246902 Sao Paulo, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Bioorganic & Medicinal Chemistry Letters; v. 26, n. 4, p. 1180-1183, FEB 15 2016.
• Citações Web of Science: 8

Resumo

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. (AU)

• Processo FAPESP: 13/20479-9 - Síntese e avaliação de compostos potencialmente ligantes de receptores H4
• Beneficiário: João Paulo dos Santos Fernandes
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 12/18756-1 - Avaliação de novas alternativas terapêuticas com fármacos sintéticos em modelos in vitro e experimentais de Leishmania (L.) infantum chagasi
• Beneficiário: André Gustavo Tempone Cardoso
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 15/11936-2 - Emprego da quimiodiversidade de espécies vegetais de áreas remanescentes da Mata Atlântica do Estado de São Paulo na seleção de protótipos biologicamente ativos
• Beneficiário: João Henrique Ghilardi Lago
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 14/16564-3 - Síntese e avaliação da atividade de derivados do gibilimbol B em Trypanosoma cruzi
• Beneficiário: Marina Themoteo Varela
• Modalidade de apoio: Bolsas no Brasil - Iniciação Científica