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

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.

Graphical Abstract

Keywords:

• Neglected diseases
• cell death
• Leishmaniasis
• parasite
• Amazonia
• 4-methoxy-6-(1112-methylenedioxy-trans-styryl)-2-pyrone

Disclosure statement

On behalf of all authors, the corresponding author states that there is no conflict of interest.

Correction Statement

This article has been republished with minor changes. These changes do not impact the academic content of the article.

Additional information

Funding

This work was supported by Brazilian research agencies Capes, CNPq, Araucaria Foundation, FAPEAM, Finep, COMCAP – UEM.