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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| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2025-02-01
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| Series: | Molecules |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1420-3049/30/5/1093 |
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| Summary: | <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. |
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| ISSN: | 1420-3049 |