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

Abstract

Hypnophilin and panepoxydone, terpenoids isolated from Lentinus strigosus, have significant inhibitory activity on Trypanosoma 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.

• 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
• Journal: Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas (Braz J Med Biol Res) Vol. 43 Issue 11 Pg. 1054-61 (Nov 2010) ISSN: 1414-431X [Electronic] Brazil
• PMID: 21088803 (Publication Type: Journal Article)

Chemical References

• Antigens, CD
• Antiprotozoal Agents
• Bridged Bicyclo Compounds, Heterocyclic
• Plant Extracts
• Sesquiterpenes
• panepoxydone
• hypnophilin

Topics

• Antigens, CD (drug effects)
• Antiprotozoal Agents (pharmacology)
• Bridged Bicyclo Compounds, Heterocyclic (isolation & purification, pharmacology)
• Cell Proliferation (drug effects)
• Drug Design
• Humans
• Leishmania (drug effects)
• Lentinula (chemistry)
• Leukocytes, Mononuclear (drug effects)
• Plant Extracts (pharmacology)
• Sesquiterpenes (isolation & purification, pharmacology)
• Trypanosoma cruzi (drug effects)