Antiprotozoal Aminosteroids from <i>Pachysandra terminalis</i>
<i>Trypanosoma brucei rhodesiense</i> (<i>Tbr</i>) and <i>Plasmodium falciparum</i> (<i>Pf</i>) are protozoan parasites that cause severe diseases, namely, Human African Trypanosomiasis (HAT) and Malaria. Due to limited treatment options, there is an u...
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2025-02-01
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| author | Lizanne Schäfer Monica Cal Marcel Kaiser Pascal Mäser Thomas J. Schmidt |
| author_facet | Lizanne Schäfer Monica Cal Marcel Kaiser Pascal Mäser Thomas J. Schmidt |
| author_sort | Lizanne Schäfer |
| collection | DOAJ |
| description | <i>Trypanosoma brucei rhodesiense</i> (<i>Tbr</i>) and <i>Plasmodium falciparum</i> (<i>Pf</i>) are protozoan parasites that cause severe diseases, namely, Human African Trypanosomiasis (HAT) and Malaria. Due to limited treatment options, there is an urgent need for new antiprotozoal drugs. <i>Pachysandra terminalis</i> (<i>P. terminalis</i>), a plant belonging to the family Buxaceae, is known as a rich source of aminosteroid alkaloids, and a previous study of our working group already showed that the alkaloid-enriched fraction of <i>P. terminalis</i> aerial parts showed promising activity against protozoan parasites. In the present study, the alkaloid-enriched fraction obtained from a 75% ethanol extract of aerial parts was separated to isolate a chemically diverse array of <i>Pachysandra</i> alkaloids for assessment of their antiprotozoal activity and later structure–activity studies. This work yielded a new megastigmane alkaloid (<b>1</b>), 7 new aminosteroids (<b>2</b>, <b>7</b>, <b>16</b>, <b>17</b>, <b>18</b>, <b>19</b>, <b>20</b>), along with 10 known aminosteroids (<b>3</b>–<b>5</b>, <b>8</b>, <b>10</b>–<b>15</b>) and 2 artifacts (<b>6</b>, <b>9</b>) that were formed during the isolation process. The structures were elucidated by UHPLC/+ESI-QqTOF-MS/MS, as well as extensive 1- and 2D-NMR measurements. The extract and its fractions, as well as the isolated compounds, were tested in vitro against <i>Tbr</i> and <i>Pf,</i> as well as cytotoxicity against mammalian cells (L6 cell line). The activity (IC<sub>50</sub> values) of the isolated alkaloids ranged between 0.11 and 26 µM (<i>Tbr</i>) and 0.39 and 80 µM (<i>Pf</i>). 3α,4α-diapachysanaximine A (<b>7</b>) showed the highest activity against <i>Tbr</i> (IC<sub>50</sub> = 0.11 µM) with a selectivity index (SI) of 133 and was also quite active against <i>Pf</i> with IC<sub>50</sub> = 0.63 µM (SI = 23). This compound is, therefore, a promising new antiprotozoal target for further investigations. |
| format | Article |
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| institution | DOAJ |
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| publishDate | 2025-02-01 |
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| spelling | doaj-art-bcf9ee1f011545e690a959d68ca53fe72025-08-20T02:59:15ZengMDPI AGMolecules1420-30492025-02-01305109310.3390/molecules30051093Antiprotozoal Aminosteroids from <i>Pachysandra terminalis</i>Lizanne Schäfer0Monica Cal1Marcel Kaiser2Pascal Mäser3Thomas J. Schmidt4University of Münster, Institute of Pharmaceutical Biology and Phytochemistry (IPBP), PharmaCampus Corrensstraße 48, D-48149 Münster, GermanySwiss Tropical and Public Health Institute (Swiss TPH), Kreuzstrasse 2, CH-4123 Allschwil, SwitzerlandSwiss Tropical and Public Health Institute (Swiss TPH), Kreuzstrasse 2, CH-4123 Allschwil, SwitzerlandSwiss Tropical and Public Health Institute (Swiss TPH), Kreuzstrasse 2, CH-4123 Allschwil, SwitzerlandUniversity of Münster, Institute of Pharmaceutical Biology and Phytochemistry (IPBP), PharmaCampus Corrensstraße 48, D-48149 Münster, Germany<i>Trypanosoma brucei rhodesiense</i> (<i>Tbr</i>) and <i>Plasmodium falciparum</i> (<i>Pf</i>) are protozoan parasites that cause severe diseases, namely, Human African Trypanosomiasis (HAT) and Malaria. Due to limited treatment options, there is an urgent need for new antiprotozoal drugs. <i>Pachysandra terminalis</i> (<i>P. terminalis</i>), a plant belonging to the family Buxaceae, is known as a rich source of aminosteroid alkaloids, and a previous study of our working group already showed that the alkaloid-enriched fraction of <i>P. terminalis</i> aerial parts showed promising activity against protozoan parasites. In the present study, the alkaloid-enriched fraction obtained from a 75% ethanol extract of aerial parts was separated to isolate a chemically diverse array of <i>Pachysandra</i> alkaloids for assessment of their antiprotozoal activity and later structure–activity studies. This work yielded a new megastigmane alkaloid (<b>1</b>), 7 new aminosteroids (<b>2</b>, <b>7</b>, <b>16</b>, <b>17</b>, <b>18</b>, <b>19</b>, <b>20</b>), along with 10 known aminosteroids (<b>3</b>–<b>5</b>, <b>8</b>, <b>10</b>–<b>15</b>) and 2 artifacts (<b>6</b>, <b>9</b>) that were formed during the isolation process. The structures were elucidated by UHPLC/+ESI-QqTOF-MS/MS, as well as extensive 1- and 2D-NMR measurements. The extract and its fractions, as well as the isolated compounds, were tested in vitro against <i>Tbr</i> and <i>Pf,</i> as well as cytotoxicity against mammalian cells (L6 cell line). The activity (IC<sub>50</sub> values) of the isolated alkaloids ranged between 0.11 and 26 µM (<i>Tbr</i>) and 0.39 and 80 µM (<i>Pf</i>). 3α,4α-diapachysanaximine A (<b>7</b>) showed the highest activity against <i>Tbr</i> (IC<sub>50</sub> = 0.11 µM) with a selectivity index (SI) of 133 and was also quite active against <i>Pf</i> with IC<sub>50</sub> = 0.63 µM (SI = 23). This compound is, therefore, a promising new antiprotozoal target for further investigations.https://www.mdpi.com/1420-3049/30/5/1093<i>Pachysandra terminalis</i>Buxaceaeaminosteroids<i>Plasmodium falciparum</i><i>Trypanosoma brucei</i>natural products |
| spellingShingle | Lizanne Schäfer Monica Cal Marcel Kaiser Pascal Mäser Thomas J. Schmidt Antiprotozoal Aminosteroids from <i>Pachysandra terminalis</i> Molecules <i>Pachysandra terminalis</i> Buxaceae aminosteroids <i>Plasmodium falciparum</i> <i>Trypanosoma brucei</i> natural products |
| title | Antiprotozoal Aminosteroids from <i>Pachysandra terminalis</i> |
| title_full | Antiprotozoal Aminosteroids from <i>Pachysandra terminalis</i> |
| title_fullStr | Antiprotozoal Aminosteroids from <i>Pachysandra terminalis</i> |
| title_full_unstemmed | Antiprotozoal Aminosteroids from <i>Pachysandra terminalis</i> |
| title_short | Antiprotozoal Aminosteroids from <i>Pachysandra terminalis</i> |
| title_sort | antiprotozoal aminosteroids from i pachysandra terminalis i |
| topic | <i>Pachysandra terminalis</i> Buxaceae aminosteroids <i>Plasmodium falciparum</i> <i>Trypanosoma brucei</i> natural products |
| url | https://www.mdpi.com/1420-3049/30/5/1093 |
| work_keys_str_mv | AT lizanneschafer antiprotozoalaminosteroidsfromipachysandraterminalisi AT monicacal antiprotozoalaminosteroidsfromipachysandraterminalisi AT marcelkaiser antiprotozoalaminosteroidsfromipachysandraterminalisi AT pascalmaser antiprotozoalaminosteroidsfromipachysandraterminalisi AT thomasjschmidt antiprotozoalaminosteroidsfromipachysandraterminalisi |