In vitro activity of hypnophilin from Lentinus strigosus: a potential prototype for Chagas disease and leishmaniasis chemotherapy

• Main Authors: E.M. Souza-Fagundes, B.B. Cota, L.H. Rosa, A.J. Romanha, R. Corrêa-Oliveira, C.A. Rosa, C.L. Zani, A. Teixeira-Carvalho, O.A. Martins-Filho
• Format: Article
• Language: English
• Published: Associação Brasileira de Divulgação Científica 2010-11-01
• Series: Brazilian Journal of Medical and Biological Research
• Subjects: Chagas disease; Leishmaniasis; Chemotherapy; Immunomodulation; Hypnophilin; Lentinus strigosus
• Online Access: http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2010001100007

Hypnophilin and panepoxydone, terpenoids isolated from Lentinus strigosus, have significant inhibitory activity onTrypanosoma cruzi trypanothione reductase (TR). Although they have similar TR inhibitory activity at 10 μg/mL (40.3 μM and 47.6 μM for hypnophilin and panepoxydone, respectively; ~100%), hypnophilin has a slightly greater inhibitory activity (~71%) on T. cruzi amastigote (AMA) growth in vitro as well as on in vitro phytohemagglutinin (PHA)-induced peripheral blood mononuclear (PBMC) proliferation (~70%) compared to panepoxydone (69% AMA inhibition and 91% PBMC inhibition). Hypnophilin and panepoxydone at 1.25 μg/mL had 67% inhibitory activity onLeishmania (Leishmania) amazonensis amastigote-like (AMA-like) growth in vitro. The panepoxydone activity was accompanied by a significant inhibitory effect on PHA-induced PBMC proliferation, suggesting a cytotoxic action. Moreover, incubation of human PBMC with panepoxydone reduced the percentage of CD16+ and CD14+ cells and down-regulated CD19+, CD4+ and CD8+ cells, while hypnophilin did not alter any of the phenotypes analyzed. These data indicate that hypnophilin may be considered to be a prototype for the design of drugs for the chemotherapy of diseases caused by Trypanosomatidae.