Journal
BASIC & CLINICAL PHARMACOLOGY & TOXICOLOGY
Volume 120, Issue 1, Pages 52-58Publisher
WILEY-BLACKWELL
DOI: 10.1111/bcpt.12639
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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 mu M) and amastigote (IC50=1.43 mu M) forms, indicating a potent antileishmanial effect. There was no evidence of cytotoxicity to macrophages or erythrocytes at concentrations ranging from 13 to 0.5 mu M, 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.
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