Styrylpyrone, isolated from an Amazon plant, induces cell cycle arrest and autophagy in Leishmania amazonensis

Nat Prod Res. 2021 Nov;35(22):4729-4733. doi: 10.1080/14786419.2020.1715395. Epub 2020 Jan 25.

Abstract

The search for bioactive compounds against diseases is imperative and the richness of the Amazon provides a large source to be explored. Current therapies for the treatment of parasitic infections have severe side effects and low efficacy, which makes the development of an effective chemotherapy extremely important. In this study, we describe the isolation of styrylpyrone 4-methoxy-6-(11,12-methylenedioxy-trans-styryl)-2-pyrone (SP), from the Amazonian tree species, Aniba panurensis, the in vitro activity against Leishmania amazonensis promastigotes, and its in silico pharmacokinetics properties. The results showed morphological and ultrastructural alterations, cell cycle impairment, increased reactive oxygen species production, accumulation of lipid bodies and formation of autophagic vacuoles in SP-treated parasites. In silico studies revealed that the compound has a high drug-score, which is encouraging for further investigation. Our results indicate that SP is a promising drug candidate, which induces alterations in L. amazonensis leading to parasite death through cell cycle arrest and autophagy.

Keywords: 4-methoxy-6-(1112-methylenedioxy-trans-styryl)-2-pyrone; Amazonia; Leishmaniasis; Neglected diseases; cell death; parasite.

MeSH terms

  • Animals
  • Antiprotozoal Agents* / pharmacology
  • Autophagy
  • Cell Cycle Checkpoints
  • Lauraceae*
  • Leishmania mexicana*
  • Mice
  • Mice, Inbred BALB C
  • Reactive Oxygen Species

Substances

  • Antiprotozoal Agents
  • Reactive Oxygen Species