Portal de Periódicos da CAPES

Antileishmanial Acetylene Fatty Acid and Acetogenins from Seeds of Porcelia macrocarpa

2020; Brazilian Chemical Society; Linguagem: Inglês

10.21577/0103-5053.20200197

1678-4790

Ivanildo A. Brito, Emerson A. Oliveira, Mariana Helena Chaves, Fernanda Thevenard, André F. Rodrigues‐Oliveira, Gustavo Barbosa‐Reis, Patrı́cia Sartorelli, Diogo Oliveira‐Silva, André G. Tempone, Thais A. Costa‐Silva, João Henrique G. Lago,

Phytochemical compounds biological activities

In the present work five acetylene derivatives (1-5), including three unknowns (1, 3 and 4), were isolated from seeds of Porcelia macrocarpa (Annonaceae).The structures of isolated compounds were determined as docos-13-yn-21-enoic acid (1), 3-hydroxy-4-methylene-2-(eicos-11'-yn-19'-enyl)but-2-enolide (2), 3-hydroxy-4-methylene-2-(octadec-9'-yn-17'-enyl)but-2-enolide (3), 3-hydroxy-4-methylene-2-(hexadec-7'-yn-15'-enyl)but-2-enolide (4), and (2S,3R,4R)-3-hydroxy-4-methyl-2-(eicos-11'-yn-19'-enyl)butanolide ( 5) by analysis of nuclear magnetic resonance (NMR) and electrospray ionization high-resolution mass spectrometry (ESI-HRMS) data.Moreover, all isolated compounds demonstrated selectivity towards intracellular amastigotes of Leishmania (L.) infantum, especially 2-4 with 50% inhibitory concentration (IC 50 ) values of 9.2, 10.4 and 11.0 µM, respectively, indicating superior activity of that determined to positive control miltefosine (IC 50 of 17.8 µM).Furthermore, these compounds showed higher selectivity index (SI) in comparison with miltefosine.Since related acetylene fatty acid 1 displayed reduced antiparasitic potential (IC 50 of 48.5 µM), the obtained results suggested that the γ-lactone plays an important role in the antileishmanial activity.However, 2-4 exhibited cytotoxicity to mammalian NCTC cells (CC 50 ca.80 µM), which could be a result of the presence of a conjugated carbonyl system in the lactone ring, since 5, the only acetogenin that presents the saturated ring, lacked mammalian cytotoxicity (CC 50 > 200 µM).