In Vitro Effects of the Neolignan 2,3-Dihydrobenzofuran Against Leishmania Amazonensis

Basic Clin Pharmacol Toxicol. 2017 Jan;120(1):52-58. doi: 10.1111/bcpt.12639. Epub 2016 Sep 16.


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.

MeSH terms

  • Animals
  • Antiprotozoal Agents / adverse effects
  • Antiprotozoal Agents / pharmacology*
  • Benzofurans / adverse effects
  • Benzofurans / pharmacology*
  • Erythrocytes / drug effects
  • Hemolysis / drug effects
  • Humans
  • Hydroxylation
  • Inhibitory Concentration 50
  • Leishmania / drug effects*
  • Leishmania / growth & development
  • Leishmania / physiology
  • Lignans / adverse effects
  • Lignans / pharmacology*
  • Lysosomes / drug effects
  • Lysosomes / enzymology
  • Macrophage Activation / drug effects
  • Macrophages, Peritoneal / drug effects
  • Macrophages, Peritoneal / immunology
  • Macrophages, Peritoneal / metabolism
  • Macrophages, Peritoneal / parasitology
  • Mice, Inbred BALB C
  • Nitric Oxide / agonists
  • Nitric Oxide / metabolism
  • Osmolar Concentration
  • Phagocytosis / drug effects


  • Antiprotozoal Agents
  • Benzofurans
  • Lignans
  • Nitric Oxide