title: In Vitro Effects of the Neolignan 2,3-Dihydrobenzofuran Against Leishmania Amazonensis.
abstract: Leishmaniasis is an infectious disease complex caused by protozoa from the Leishmania genus, which presents a broad spectrum of clinical manifestations: cutaneous, mucocutaneous and visceral forms. The current treatments are unsatisfactory considering that few drugs are available and present some level of toxicity. Many lignans and neolignans have been used for the development of new antileishmania drugs. The capability in vitro of the neolignan 2,3-dihydrobenzofuran (2,3-DBF), a commonly found constituent of propolis and other plants, to inhibit the growth of promastigote and macrophage-internalized amastigote forms of Leishmania amazonensis was investigated. The cytotoxicity of this compound was assessed by MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) test in BALB/c murine macrophages and human erythrocyte lysis assay. The 2,3-DBF was active against promastigote (IC50=1.042 μM) and amastigote (IC50=1.43 μM) forms, indicating a potent antileishmanial effect. There was no evidence of cytotoxicity to macrophages or erythrocytes at concentrations ranging from 13 to 0.5 μM, after 48 hr of exposure. The antileishmanial activity is probably mediated by the activation of macrophages, because treatment with 2,3-DBF increases both phagocytic and lysosomal activities, as well as the nitrite (NO2-) levels. These results suggest that 2,3-DBF may be a potential candidate for the development of a new promising antileishmanial drug. Further studies are needed to determine its potential in vivo effect as well as additional mechanisms underlying the antileishmanial and immunomodulatory activities.
authors.affiliation: Medicinal Plants Research Center, Federal University of Piauí, Teresina, PI, Brazil.
authors.forename: Luciano Gomes
authors.initials: LG
authors.lastname: de Castro Oliveira
authors.affiliation: Medicinal Plants Research Center, Federal University of Piauí, Teresina, PI, Brazil.
authors.forename: Lucas Moreira
authors.initials: LM
authors.lastname: Brito
authors.affiliation: Medicinal Plants Research Center, Federal University of Piauí, Teresina, PI, Brazil.
authors.forename: Michel Muálem
authors.initials: MM
authors.lastname: de Moraes Alves
authors.affiliation: Medicinal Plants Research Center, Federal University of Piauí, Teresina, PI, Brazil.
authors.forename: Layane Valéria
authors.initials: LV
authors.lastname: Amorim
authors.affiliation: Medicinal Plants Research Center, Federal University of Piauí, Teresina, PI, Brazil.
authors.forename: Enoque Pereira Costa
authors.initials: EP
authors.lastname: Sobrinho-Júnior
authors.affiliation: Medicinal Plants Research Center, Federal University of Piauí, Teresina, PI, Brazil.
authors.forename: Camila Ernanda Sousa
authors.initials: CE
authors.lastname: de Carvalho
authors.affiliation: Medicinal Plants Research Center, Federal University of Piauí, Teresina, PI, Brazil.
authors.forename: Klinger Antonio
authors.initials: KA
authors.lastname: da Franca Rodrigues
authors.affiliation: Medicinal Plants Research Center, Federal University of Piauí, Teresina, PI, Brazil.|Department of Biophysics and Physiology, Federal University of Piauí, Teresina, PI, Brazil.
authors.forename: Daniel Dias Rufino
authors.initials: DD
authors.lastname: Arcanjo
authors.affiliation: Department of Chemistry, Federal University of Piauí, Teresina, PI, Brazil.
authors.forename: Antônia Maria
authors.initials: AM
authors.lastname: das Graças Lopes Citó
authors.affiliation: Medicinal Plants Research Center, Federal University of Piauí, Teresina, PI, Brazil.|Department of Biochemistry and Pharmacology, Federal University of Piauí, Teresina, PI, Brazil.
authors.forename: Fernando Aécio
authors.initials: FA
authors.lastname: de Amorim Carvalho
mesh_terms: D000818:Animals; D000981:Antiprotozoal Agents / Q000009:adverse effects / Q000494:pharmacology*; D001572:Benzofurans / Q000009:adverse effects / Q000494:pharmacology*; D004912:Erythrocytes / Q000187:drug effects; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D006900:Hydroxylation; D020128:Inhibitory Concentration 50; D007891:Leishmania / Q000187:drug effects* / Q000254:growth & development / Q000502:physiology; D017705:Lignans / Q000009:adverse effects / Q000494:pharmacology*; D008247:Lysosomes / Q000187:drug effects / Q000201:enzymology; D008262:Macrophage Activation / Q000187:drug effects; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000469:parasitology; D008807:Mice, Inbred BALB C; D009569:Nitric Oxide / Q000819:agonists / Q000378:metabolism; D009994:Osmolar Concentration; D010587:Phagocytosis / Q000187:drug effects
chemical_list: D000981:Antiprotozoal Agents; D001572:Benzofurans; D017705:Lignans; D009569:Nitric Oxide