title: 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.affiliation: Departamento de Fisiologia e Biofísica, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brasil.
authors.forename: E M
authors.initials: EM
authors.lastname: Souza-Fagundes
authors.forename: B B
authors.initials: BB
authors.lastname: Cota
authors.forename: L H
authors.initials: LH
authors.lastname: Rosa
authors.forename: A J
authors.initials: AJ
authors.lastname: Romanha
authors.forename: R
authors.initials: R
authors.lastname: Corrêa-Oliveira
authors.forename: C A
authors.initials: CA
authors.lastname: Rosa
authors.forename: C L
authors.initials: CL
authors.lastname: Zani
authors.forename: A
authors.initials: A
authors.lastname: Teixeira-Carvalho
authors.forename: O A
authors.initials: OA
authors.lastname: Martins-Filho
mesh_terms: D015703:Antigens, CD / Q000187:drug effects; D000981:Antiprotozoal Agents / Q000494:pharmacology*; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000302:isolation & purification / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D015195:Drug Design; D006801:Humans; D007891:Leishmania / Q000187:drug effects*; D020074:Lentinula / Q000737:chemistry*; D007963:Leukocytes, Mononuclear / Q000187:drug effects; D010936:Plant Extracts / Q000494:pharmacology*; D012717:Sesquiterpenes / Q000302:isolation & purification / Q000494:pharmacology*; D014349:Trypanosoma cruzi / Q000187:drug effects*
chemical_list: D015703:Antigens, CD; D000981:Antiprotozoal Agents; D019086:Bridged Bicyclo Compounds, Heterocyclic; D010936:Plant Extracts; D012717:Sesquiterpenes; C101349:panepoxydone; C446680:hypnophilin