Lignans Isolated from Piper truncatum Act as New Potent Antitrypanosomal Compounds

Autor(es)

de M. Goncalves, Marina ; Totini, Carlos H. ; De Castro, Erica V. ; Albuquerque, Vanessa ; Antar, Guilherme M. ; Tempone, Andre G. ; Lago, Joao Henrique G.

• Tipo de documento: Artigo Científico
• Fonte: CHEMISTRY & BIODIVERSITY; v. 21, n. 5, p. 6-pg., 2024-04-12.

Resumo

The hexane extract from twigs of Piper truncatum Vell (Piperaceae) displayed activity against Trypanosoma cruzi and was subjected to chromatographic steps to afford six dibenzylbutyrolactolic lignans, being four knowns: cubebin (1), (-)-9 alpha-O-methylcubebin (2), (+)-9 beta-O-methylcubebinin (3) and 3,4-dimethoxy-3,4-demethylenedioxycubebin (4) as well as two new, named truncatin A (5) and B (6). Initially, in vitro activity against trypomastigotes was evaluated and compounds 1, 4 and 6 exhibited EC50 values of 41.6, 21.0 and 39.6 mu M, respectively. However, when tested against amastigotes, the relevant clinical form in the chronic phase of Chagas disease, compounds 1-6 displayed activities with EC50 values ranging from 1.6 to 13.7 mu M. In addition, the mammalian cytotoxicity of compounds 1-6 was evaluated against murine fibroblasts (NCTC). Compounds 2, 3 and 4 exhibited reduced toxicity against NCTC cells (CC50>200 mu M), resulting in SI values of>21.9,>14.5 and>121.9, respectively. Compound 4 showed the highest potency with an SI value twice superior to that determined by the standard drug benznidazole (SI>54.6) against the intracellular amastigotes. These data suggest that lignan 4 can be considered a possible scaffold for designing a new drug candidate for Chagas disease. (AU)

• Processo FAPESP: 21/04464-8 - Protótipos microbianos e vegetais como candidatos a fármacos para protozooses negligenciadas e bactérias multirresistentes
• Beneficiário: André Gustavo Tempone Cardoso
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 23/12447-1 - Busca de metabólitos especializados oriundos da biodiversidade florística brasileira como candidatos a fármacos para doenças tropicais negligenciadas
• Beneficiário: João Henrique Ghilardi Lago
• Modalidade de apoio: Auxílio à Pesquisa - Programa BIOTA - Regular