Antileishmanial Effects of Acetylene Acetogenins from Seeds of <i>Porcelia macrocarpa</i> (Warm.) R.E. Fries (Annonaceae) and Semisynthetic Derivatives
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, (<i>2S</i>,<i>3...
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MDPI AG
2022-01-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/27/3/893 |
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| author | Ivanildo A. Brito Fernanda Thevenard Thais A. Costa-Silva Samuel S. Oliveira Rodrigo L. O. R. Cunha Emerson A. de Oliveira Patricia Sartorelli Rafael C. Guadagnin Maiara M. Romanelli Andre G. Tempone João Henrique G. Lago |
| author_facet | Ivanildo A. Brito Fernanda Thevenard Thais A. Costa-Silva Samuel S. Oliveira Rodrigo L. O. R. Cunha Emerson A. de Oliveira Patricia Sartorelli Rafael C. Guadagnin Maiara M. Romanelli Andre G. Tempone João Henrique G. Lago |
| author_sort | Ivanildo A. Brito |
| collection | DOAJ |
| description | 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, (<i>2S</i>,<i>3R</i>,<i>4R</i>)-3-hydroxy-4-methyl-2-(<i>n</i>-eicos-11′-yn-19′-enyl)butanolide (<b>1</b>) and (<i>2S</i>,<i>3R</i>,<i>4R</i>)-3-hydroxy-4-methyl-2-(<i>n</i>-eicos-11′-ynyl)butanolide (<b>2</b>), from the seeds of <i>Porcelia macrocarpa</i> (Warm.) R.E. Fries (Annonaceae). Using an ex-vivo assay, compound <b>1</b> showed an IC<sub>50</sub> value of 29.9 μM against the intracellular amastigote forms of <i>Leishmania (L.) infantum</i>, whereas compound <b>2</b> 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 (<b>1a</b> and <b>2a</b>) and eliminated (<b>1b</b> and <b>2b</b>) derivatives, since only compounds containing a double bond at C-19 displayed activity, resulting in IC<sub>50</sub> values of 43.3 μM (<b>1a</b>) and 23.1 μM (<b>1b</b>). In order to evaluate the effect of the triple bond in the antileishmanial potential, the mixture of compounds <b>1</b> + <b>2</b> was subjected to catalytic hydrogenation to afford a compound <b>3</b> containing a saturated side chain. The antiparasitic assays performed with compound <b>3</b>, acetylated (<b>3a</b>), and eliminated (<b>3b</b>) derivatives confirmed the lack of activity. Furthermore, an in-silico study using the SwissADME online platform was performed to bioactive compounds <b>1</b>, <b>1a</b>, and <b>1b</b> 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 <b>1 + 2</b>, <b>1a + 2a</b>, and <b>1b + 2b</b> were prepared and exhibited IC<sub>50</sub> values ranging from 7.9 to 38.4 μM, with no toxicity for NCTC mammalian cells (CC<sub>50</sub> > 200 μM). Selectivity indexes to these mixtures ranged from >5.2 to >25.3. The obtained results indicate that seeds of <i>Porcelia macrocarpa</i> are a promising source of interesting prototypes for further modifications aiming at the discovery of new antileishmanial drugs. |
| first_indexed | 2024-03-09T23:28:11Z |
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| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-09T23:28:11Z |
| publishDate | 2022-01-01 |
| publisher | MDPI AG |
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| series | Molecules |
| spelling | doaj.art-531831dd09e145699112039faad91c0d2023-11-23T17:14:13ZengMDPI AGMolecules1420-30492022-01-0127389310.3390/molecules27030893Antileishmanial Effects of Acetylene Acetogenins from Seeds of <i>Porcelia macrocarpa</i> (Warm.) R.E. Fries (Annonaceae) and Semisynthetic DerivativesIvanildo A. Brito0Fernanda Thevenard1Thais A. Costa-Silva2Samuel S. Oliveira3Rodrigo L. O. R. Cunha4Emerson A. de Oliveira5Patricia Sartorelli6Rafael C. Guadagnin7Maiara M. Romanelli8Andre G. Tempone9João Henrique G. Lago10Human and Natural Science Center, Universidade Federal do ABC, São Paulo 09210-580, BrazilHuman and Natural Science Center, Universidade Federal do ABC, São Paulo 09210-580, BrazilHuman and Natural Science Center, Universidade Federal do ABC, São Paulo 09210-580, BrazilHuman and Natural Science Center, Universidade Federal do ABC, São Paulo 09210-580, BrazilHuman and Natural Science Center, Universidade Federal do ABC, São Paulo 09210-580, BrazilDepartament of Chemistry, Universidade Federal de São Paulo, São Paulo 09972-270, BrazilDepartament of Chemistry, Universidade Federal de São Paulo, São Paulo 09972-270, BrazilDepartament of Chemistry, Universidade Federal de São Paulo, São Paulo 09972-270, BrazilDepartment of Parasitology, Instituto Adolfo Lutz, São Paulo 01246-902, BrazilDepartment of Parasitology, Instituto Adolfo Lutz, São Paulo 01246-902, BrazilHuman and Natural Science Center, Universidade Federal do ABC, São Paulo 09210-580, BrazilAs 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, (<i>2S</i>,<i>3R</i>,<i>4R</i>)-3-hydroxy-4-methyl-2-(<i>n</i>-eicos-11′-yn-19′-enyl)butanolide (<b>1</b>) and (<i>2S</i>,<i>3R</i>,<i>4R</i>)-3-hydroxy-4-methyl-2-(<i>n</i>-eicos-11′-ynyl)butanolide (<b>2</b>), from the seeds of <i>Porcelia macrocarpa</i> (Warm.) R.E. Fries (Annonaceae). Using an ex-vivo assay, compound <b>1</b> showed an IC<sub>50</sub> value of 29.9 μM against the intracellular amastigote forms of <i>Leishmania (L.) infantum</i>, whereas compound <b>2</b> 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 (<b>1a</b> and <b>2a</b>) and eliminated (<b>1b</b> and <b>2b</b>) derivatives, since only compounds containing a double bond at C-19 displayed activity, resulting in IC<sub>50</sub> values of 43.3 μM (<b>1a</b>) and 23.1 μM (<b>1b</b>). In order to evaluate the effect of the triple bond in the antileishmanial potential, the mixture of compounds <b>1</b> + <b>2</b> was subjected to catalytic hydrogenation to afford a compound <b>3</b> containing a saturated side chain. The antiparasitic assays performed with compound <b>3</b>, acetylated (<b>3a</b>), and eliminated (<b>3b</b>) derivatives confirmed the lack of activity. Furthermore, an in-silico study using the SwissADME online platform was performed to bioactive compounds <b>1</b>, <b>1a</b>, and <b>1b</b> 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 <b>1 + 2</b>, <b>1a + 2a</b>, and <b>1b + 2b</b> were prepared and exhibited IC<sub>50</sub> values ranging from 7.9 to 38.4 μM, with no toxicity for NCTC mammalian cells (CC<sub>50</sub> > 200 μM). Selectivity indexes to these mixtures ranged from >5.2 to >25.3. The obtained results indicate that seeds of <i>Porcelia macrocarpa</i> are a promising source of interesting prototypes for further modifications aiming at the discovery of new antileishmanial drugs.https://www.mdpi.com/1420-3049/27/3/893<i>Porcelia macrocarpa</i>acetylene acetogenins<i>Leishmania (L.) infantum</i>leishmaniasis |
| spellingShingle | Ivanildo A. Brito Fernanda Thevenard Thais A. Costa-Silva Samuel S. Oliveira Rodrigo L. O. R. Cunha Emerson A. de Oliveira Patricia Sartorelli Rafael C. Guadagnin Maiara M. Romanelli Andre G. Tempone João Henrique G. Lago Antileishmanial Effects of Acetylene Acetogenins from Seeds of <i>Porcelia macrocarpa</i> (Warm.) R.E. Fries (Annonaceae) and Semisynthetic Derivatives Molecules <i>Porcelia macrocarpa</i> acetylene acetogenins <i>Leishmania (L.) infantum</i> leishmaniasis |
| title | Antileishmanial Effects of Acetylene Acetogenins from Seeds of <i>Porcelia macrocarpa</i> (Warm.) R.E. Fries (Annonaceae) and Semisynthetic Derivatives |
| title_full | Antileishmanial Effects of Acetylene Acetogenins from Seeds of <i>Porcelia macrocarpa</i> (Warm.) R.E. Fries (Annonaceae) and Semisynthetic Derivatives |
| title_fullStr | Antileishmanial Effects of Acetylene Acetogenins from Seeds of <i>Porcelia macrocarpa</i> (Warm.) R.E. Fries (Annonaceae) and Semisynthetic Derivatives |
| title_full_unstemmed | Antileishmanial Effects of Acetylene Acetogenins from Seeds of <i>Porcelia macrocarpa</i> (Warm.) R.E. Fries (Annonaceae) and Semisynthetic Derivatives |
| title_short | Antileishmanial Effects of Acetylene Acetogenins from Seeds of <i>Porcelia macrocarpa</i> (Warm.) R.E. Fries (Annonaceae) and Semisynthetic Derivatives |
| title_sort | antileishmanial effects of acetylene acetogenins from seeds of i porcelia macrocarpa i warm r e fries annonaceae and semisynthetic derivatives |
| topic | <i>Porcelia macrocarpa</i> acetylene acetogenins <i>Leishmania (L.) infantum</i> leishmaniasis |
| url | https://www.mdpi.com/1420-3049/27/3/893 |
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