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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

Antiparasitic activity of new gibbilimbol analogues and SAR analysis through efficiency and statistical methods

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Autor(es):
Varela, Marina T. [1] ; Romaneli, Maiara M. [2] ; Lima, Marta L. [2, 3] ; Borborema, Samanta E. T. [2] ; Tempone, Andre G. [2] ; Fernandes, Joao P. S. [1]
Número total de Autores: 6
Afiliação do(s) autor(es):
[1] Univ Fed Sao Paulo, Dept Ciencias Farmaceut, Rua Sao Nicolau 210, BR-09913030 Diadema, SP - Brazil
[2] Adolfo Lutz Inst, Ctr Parasitol & Micol, Av Dr Arnaldo 355, BR-01246000 Sao Paulo, SP - Brazil
[3] Univ Sao Paulo, Inst Med Trop Sao Paulo, Av Dr Eneas Carvalho de Aguiar 470, BR-05403000 Sao Paulo, SP - Brazil
Número total de Afiliações: 3
Tipo de documento: Artigo Científico
Fonte: European Journal of Pharmaceutical Sciences; v. 122, p. 31-41, SEP 15 2018.
Citações Web of Science: 4
Resumo

Chagas' disease and leishmaniasis are parasitic infections enrolled among the neglected tropical diseases, which urge for new treatments. In the search for new chemical entities as prototypes, gibbilimbols A/B have shown antiparasitic activity against Trypanosoma cruzi and Leishmania infantum, and then a set of analogues (LINS03 series) of this natural product were synthesized and evaluated in vitro against the parasites. In the present paper we reported five new compounds with activity against these protozoan parasites, and quite low cytotoxicity. Moreover, the interference of plasma membrane permeability of these analogues were also evaluated. We found that {[}(4-methoxyphenyl) methyl] octylamine (4) was noteworthy due to its high activity against the amastigote form of both parasites (IC50 1.3-5.8 mu M) and good selectivity index. In order to unveil the SAR for this chemotype, we also presented a group efficiency analysis and PCA and HCA study, which indicated that the methoxyl provides good activity with lower cytotoxicity to mammalian cells. The results from SAR analyses suggest different mechanisms of action between the neutral and basic compounds. In summary, the analogues represent important activity against these parasites and must be prototypes for further exploitation. (AU)

Processo FAPESP: 15/23403-9 - Estudo Pré-Clínico Racional de Novos Candidatos a Fármacos em Protozooses Negligenciadas Utilizando Abordagens Farmacocinéticas
Beneficiário:André Gustavo Tempone Cardoso
Linha de fomento: Auxílio à Pesquisa - Regular
Processo FAPESP: 16/00195-4 - Síntese e avaliação da atividade de alquilfenóis substituídos em Trypanosoma cruzi
Beneficiário:Marina Themoteo Varela
Linha de fomento: Bolsas no Brasil - Mestrado
Processo FAPESP: 16/25028-3 - Anti-histamínicos H3R/H4R como agentes pró-cognitivos: uma abordagem multialvo
Beneficiário:João Paulo dos Santos Fernandes
Linha de fomento: Auxílio à Pesquisa - Regular