Antileishmanial Acetylene Fatty Acid and Acetogenins from Seeds of Porcelia macrocarpa

• Published in: Journal of the Brazilian Chemical Society Vol. 32; no. 2; pp. 447 - 453
• Main Authors: Brito, Ivanildo, Oliveira, Emerson, Chaves, Mariana, Thevenard, Fernanda, Rodrigues-Oliveira, André, Barbosa-Reis, Gustavo, Sartorelli, Patricia, Oliveira-Silva, Diogo, Tempone, Andre, Costa-Silva, Thais, Lago, João Henrique
• Format: Journal Article
• Language: English
• Published: Sociedade Brasileira de Química 01-02-2021
• Subjects: CHEMISTRY, MULTIDISCIPLINARY; Porcelia macrocarpa; acetylene acetogenins; anti-Leishmania (L.) infantum
• ISSN: 0103-5053; 1678-4790
• DOI: 10.21577/0103-5053.20200197

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 (IC50) values of 9.2, 10.4 and 11.0 µM, respectively, indicating superior activity of that determined to positive control miltefosine (IC50 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 (IC50 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 (CC50 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 (CC50 > 200 µM).