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

Autor(es)

Varela, Marina T. ^[1] ; Lima, Marta L. ^{[2, 3]} ; Galuppo, Mariana K. ^[2] ; Tempone, Andre G. ^[2] ; de Oliveira, Alberto ^[4] ; Lago, Joao Henrique G. ^[5] ; Fernandes, Joao Paulo S. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Fed Sao Paulo, Dept Ciencias Farmaceut, Diadema, SP - Brazil

^[2] Adolfo Lutz Inst, Ctr Parasitol & Micol, Sao Paulo, SP - Brazil

^[3] Univ Sao Paulo, Inst Med Trop Sao Paulo, Sao Paulo, SP - Brazil

^[4] Univ Fed Uberlandia, Inst Quim, Uberlandia, MG - Brazil

^[5] Univ Fed ABC, Ctr Ciencias Nat & Humanas, Santo Andre, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: CHEMICAL BIOLOGY & DRUG DESIGN; v. 90, n. 5, p. 1007-1011, NOV 2017.
• Citações Web of Science: 8

Resumo

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. (AU)

• 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: 13/50228-8 - Componentes da biodiversidade, e seus caracteres metabólicos, de ilhas do Brasil: uma abordagem integrada
• Beneficiário: Roberto Gomes de Souza Berlinck
• Modalidade de apoio: Auxílio à Pesquisa - Programa BIOTA - Temático
• 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: 16/00195-4 - Síntese e avaliação da atividade de alquilfenóis substituídos em Trypanosoma cruzi
• Beneficiário: Marina Themoteo Varela
• Modalidade de apoio: Bolsas no Brasil - Mestrado