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

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Version 3 2022-08-03, 07:55
Version 2 2020-02-11, 07:05
Version 1 2020-01-25, 09:29
journal contribution
posted on 2022-08-03, 07:55 authored by Nilma de Souza Fernandes, Vânia Cristina Desoti, Alcilene Dias, Yasmin Cunha da Silva, Ana Paula de Azevedo dos Santos, Guilherme Matos Passarini, Celso Vataru Nakamura, Valdir Florêncio da Veiga Junior

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.

Funding

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

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