Antileishmanial Acetylene Fatty Acid and Acetogenins from Seeds of Porcelia macrocarpa

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

doi:10.21577/0103-5053.20200197

Cited by 2 publications

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“…Porcelia macrocarpa is a Brazilian plant that produces different bioactive metabolites such as terpenoids, alkaloids, acetylene fatty acids, and acetogenins [5][6][7][8][9][10][11]. In this work, two acetylene acetogenins were isolated from seeds of this plant using several chromatographic techniques, and their structures were confirmed as (2S,3R,4R)-3-hydroxy-4-methyl-2-(n-eicos-11 -yn-19 -enyl)butanolide ( 1) and (2S,3R,4R)-3-hydroxy-4-methyl-2-(n-eicos-11ynyl)butanolide ( 2) by NMR and ESI-HRMS spectral analysis (see Supplementary Material) and comparison with data described in the literature [11].…”

Section: Resultsmentioning

confidence: 99%

“…As previously reported [5][6][7], P. macrocarpa is an important source of natural antiprotozoal natural products including acetylenic fatty acids and acetogenins with anti-T. cruzi potential. Recently, our group reported the occurrence of different acetylene acetogenins and fatty acids with anti-Leishmania activity, especially against the intracellular amastigote forms [8].…”

Section: Resultsmentioning

confidence: 99%

“…Then, the macrophages were incubated with compounds or standard drug (miltefosine) in a range of 100 to 0.78 µM for 96 h at 37 • C in a 5% CO 2 -humidified incubator, using miltefosine as a standard drug. At the end of the assay, the cells were fixed in methanol, stained with Giemsa, and observed under a digital light microscope (EVOS M5000, Thermo, Waltham, MA, USA) to determine the number of infected macrophages out of 400 cells [8].…”

Section: Determination Of the Activity Against L (L) Infantum-intracellular Amastigotesmentioning

confidence: 99%

“…Additionally, these compounds induce alterations in the plasma membrane permeability and in the electric potential of th mitochondrial membrane as well as in the reactive oxygen species (ROS) levels of th parasite [6,7]. Despite the effect against T. cruzi, there is one unique study evaluating th effect of different acetogenins and fatty acid from P. macrocarpa against intracellular form of Leishmania (L.) infantum, which is the most relevant form of the parasite [8]. Aiming to discover new natural products with antiprotozoal activity, different studies with P. macrocarpa have previously been performed.…”

Section: Introductionmentioning

confidence: 99%

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Antileishmanial Effects of Acetylene Acetogenins from Seeds of Porcelia macrocarpa (Warm.) R.E. Fries (Annonaceae) and Semisynthetic Derivatives

et al. 2022

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As part of our continuous studies involving the prospection of natural products from Brazilian flora aiming at the discovery of prototypes for the development of new antiparasitic drugs, the present study describes the isolation of two natural acetylene acetogenins, (2S,3R,4R)-3-hydroxy-4-methyl-2-(n-eicos-11′-yn-19′-enyl)butanolide (1) and (2S,3R,4R)-3-hydroxy-4-methyl-2-(n-eicos-11′-ynyl)butanolide (2), from the seeds of Porcelia macrocarpa (Warm.) R.E. Fries (Annonaceae). Using an ex-vivo assay, compound 1 showed an IC50 value of 29.9 μM against the intracellular amastigote forms of Leishmania (L.) infantum, whereas compound 2 was inactive. These results suggested that the terminal double bond plays an important role in the activity. This effect was also observed for the semisynthetic acetylated (1a and 2a) and eliminated (1b and 2b) derivatives, since only compounds containing a double bond at C-19 displayed activity, resulting in IC50 values of 43.3 μM (1a) and 23.1 μM (1b). In order to evaluate the effect of the triple bond in the antileishmanial potential, the mixture of compounds 1 + 2 was subjected to catalytic hydrogenation to afford a compound 3 containing a saturated side chain. The antiparasitic assays performed with compound 3, acetylated (3a), and eliminated (3b) derivatives confirmed the lack of activity. Furthermore, an in-silico study using the SwissADME online platform was performed to bioactive compounds 1, 1a, and 1b in order to investigate their physicochemical parameters, pharmacokinetics, and drug-likeness. Despite the reduced effect against amastigote forms of the parasite to the purified compounds, different mixtures of compounds 1 + 2, 1a + 2a, and 1b + 2b were prepared and exhibited IC50 values ranging from 7.9 to 38.4 μM, with no toxicity for NCTC mammalian cells (CC50 > 200 μM). Selectivity indexes to these mixtures ranged from >5.2 to >25.3. The obtained results indicate that seeds of Porcelia macrocarpa are a promising source of interesting prototypes for further modifications aiming at the discovery of new antileishmanial drugs.

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