Antiprotozoal Aminosteroids from Pachysandra terminalis
Abstract
:1. Introduction
2. Results and Discussion
2.1. Antiprotozoal Activity of the Crude Extract and Its Fractions
2.2. Isolation and Structural Characterization of Alkaloids from Pachysandra terminals
2.3. Antiprotozoal Activity of the Isolated Compounds from Pachysandra terminalis
3. Materials and Methods
3.1. Plant Material
3.2. Extraction of the Plant Material
3.3. Isolation of Alkaloids from Pachysandra terminalis
3.3.1. Isolation of a Megastigmane and Aminosteroids from the Alkaloid Fraction
3.3.2. Isolation of Aminosteroids from the Lipophilic Residue
3.4. Analysis of the Isolated Alkaloids
3.5. Spectral Data of the Isolated Alkaloids
3.6. Biological Activity Assays
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Author Statement
References
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Pf | Tbr | Cytotox | SI (Pf) | SI (Tbr) | |
---|---|---|---|---|---|
Small scale extracts | |||||
DCM extract | 8.5 ± 0.1 | 5.6 ± 0.6 | 31 ± 8 | 3.6 | 5.5 |
Alkaloid fraction (DCM) | 0.96 ± 0.04 | 6.07 ± 0.02 | 17 ± 1 | 17.3 | 2.7 |
75% EtOH extract | 9.3 ± 0.5 | 13.15 ± 0.05 | 45 ± 2 | 4.8 | 3.4 |
Alkaloid fraction (EtOH) | 0.33 ± 0.01 | 0.85 ± 0.37 | 14 ± 1 | 41.2 | 16.0 |
Large-scale extracts and fractions | |||||
75% EtOH extract | 14 ± 1 | 52 ± 11 | 76 ± 3 | 5.6 | 1.5 |
Alkaloid fraction | 0.31 ± 0.03 | 1.8 ± 0.4 | 13 ± 3 | 41.0 | 6.9 |
Lipophilic residue | 2.5 ± 0.2 | 2.0 ± 0.2 | 15 ± 1 | 6.0 | 7.4 |
Hydrophilic residue | >50 | >100 | >100 | - | - |
Positive controls | |||||
Chloroquine | 0.002 ± 0.000 | ||||
Melarsoprol | 0.007 ± 0.002 | ||||
Podophyllotoxin | 0.009 ± 0.001 |
δH [ppm], mult., J [Hz] | ||||||||||
---|---|---|---|---|---|---|---|---|---|---|
Pos. | 1 a | 2 b | 6 b | 7 b | 9 b | 16 b | 17 b | 18 b | 19 a | 20 a |
1 | - | 2.05, m 1.20, m | 1.95, m 1.17, m | 1.73, m 1.27, m | 1.92, m 1.12, ddd (dt), 13.5, 4.1 | 2.12, m 1.31, m | 1.73, m 1.43, m | 2.17, dd, 14.4, 3.1 1.36, m | 1.79, m 0.97, m | 1.89, m 1.07, m |
2 | 2.40, d, 17.3 2.05, d, 17.3 | 1.99, m 1.74, m | 2.03, m 1.78, m | 2.12, m 2.11, m | 1.91, m 1.63, m | 4.06, dd, 3.3, 1.4 | 2.12, m 2.16, m | 4.19, d, 3.4 | 1.82, m 1.50, m | 1.83, m 1.49, m |
3 | - | 3.08, dddd (tt), 12.2, 4.1 | 3.69, dddd (tt), 12.3, 3.9 | 3.68, m | 3.19, dddd (tt), 13.2, 4.3 | 3.84, dd (t), 3.4 | 3.63, m | 4.05, dd (t), 3.5 | 2.53, m | 2.25, m |
4 | 1.87, m | 2.49, dt 12.6, 12.5, 2.6 2.45, ddd, 12.8, 4.6, 2.6 | 1.76, m 1.67, m | 5.37, dd, 12.5/4.3 | 1.67, m 1.47, m | 3.74, m | 5.46, d, 4.4 | 3.87, br s | 1.57, m 1.35, m | 2.25, m |
5 | - | - | 1.31, m | 1.73, m | 1.25, m | 1.25, m | - | 1.31, m | 1.11, m | - |
6 | 5.82, s | 5.53, dd, 4.9, 2.4 | 1.37, m, 2H | 1.79, m 1.32, m | 1.38, m, 2H | 1.86, m 1.41, m, | 1.61, m 1.36, m | 1.89, m 1.41, m | 1.29, m 1.25, m | 5.34, m |
7 | 1.71, m 1.48, m | 2.06, m 1.63, m | 1.76, m 1.02, m | 1.81, m 1.00, m | 1.74, dd 13.3/3.3 1.00, m | 1.80, m 1.05, m | 1.68, m 1.61, m | 1.82, m 1.05, m | 1.68, m 0.89, m | 1.99, m 1.55, m |
8 | 1.78, m 1.41, m | 1.56, m | 1.42, m | 1.53, m | 1.44, m | 1.51, m | 1.53, m | 1.52, m | 1.33, m | 1.45, m |
9 | 2.68, br s | 1.05, m | 0.78, m | 0.98, m | 0.79, ddd, 12.2, 10.5, 4.1 | 0.73, m | 1.17, m | 0.76, m | 0.67, m | 0.97, m |
10 | 1.05, d, 3H | - | - | - | - | - | - | - | - | - |
11 | 1.02, s, 3H | 1.62, m 1.57, m | 1.59, m 1.36, m | 1.62, m 1.40, m | 1.64, m 1.36, m | 1.55, m 1.38, m | 1.51, m 1.35, m | 1.57, m 1.40, m | 1.26, m 1.54, m | 1.43, m 1.29, m |
12 | 1.07, s, 3H | 2.03, m 1.31, m | 1.98, m 1.27, m | 1.99, m 1.34, m | 2.04, m 1.46, m | 1.96, m 1.29, m | 1.98, m 1.34, m | 1.98, m 1.32, m | 1.85, m 1.26, m | 1.85, m 1.26, m |
13 | 1.99, s, 3H | - | - | - | - | - | - | - | - | - |
14 | 2.35, s, 6H | 1.17, m | 1.18, m | 1.24, m | 1.23, m | 1.22, m | 1.26, m | 1.23, m | 1.10, m | 1.04, m |
15 | 1.78, m 1.30, m | 1.77, m 1.30, m | 1.64, m 1.29, m | 1.70, m 1.22, m | 1.82, m 1.31, m | 1.76, m 1.27, m | 1.80, m 1.30, m | 1.65, m 1.16, m | 1.65, m 1.16, m | |
16 | 1.96, m 1.54, m | 1.92, m 1.49, m | 1.90, m 1.55, m | 2.13, m 1.66, m | 1.89, m 1.51, m | 1.90, m 1.55, m | 1.91, m 1.52, m | 2.08, m 1.65, m | 2.08, m 1.65, m | |
17 | 1.59, m | 1.58, m | 1.71, m | 2.63, t, 9.1 | 1.67, m | 1.67, m | 1.68, m | 2.20, m | 2.08, m | |
18 | 0.79, s, 3H | 0.77, s, 3H | 0.79, s, 3H | 0.61, s, 3H | 0.77, s, 3H | 0.78, s, 3H | 0.78, s, 3H | 0.61, s, 3H | 0.64, s, 3H | |
19 | 1.07, s, 3H | 0.90, s, 3H | 1.05, s, 3H | 0.88, s, 3H | 1.27, s, 3H | 1.16, s, 3H | 1.30, s, 3H | 0.79, s, 3H | 0.99, s, 3H | |
20 | 3.23, m | 3.21, m | 3.38, m | - | 3.35, m | 3.36, m | 3.36, m | - | - | |
21 | 1.36, d, 6.6, 3H | 1.35, d, 6.6 3H | 1.33, d, 6.6, 3H | 2.11, s, 3H | 1.33, d, 6.7, 3H | 1.33, d, 6.6, 3H | 1.33, d, 6.6, 3H | 1.86, s, 6.6, 3H | 1.86, s, 6.6, 3H | |
22 | 2.65, s, 3H | 2.65, s, 3H | 2.88, s, 3H | 2.88, s, 3H | 2.88, s, 3H | 2.88, s, 3H | ||||
23 | 2.70, s, 3H | 2.70, s, 3H | 2.70, s, 3H | 2.70, s, 3H | ||||||
24 | 2.88, s, 6H | 3.16, s, 6H | 2.75, s, 3H | 2.84, s, 3H | 2.69, s, 3H | 2.47, s (broad), 6H | 2.38, s (broad), 6H | |||
25 | ||||||||||
1′ | 5.30, s | - | - | - | - | |||||
2′ | - | 5.83, sep, 1.3 | - | - | ||||||
3′/7′ | 7.53, m | - | 8.20, m | 7.87, dd, 7.3, 1.0, 2H | ||||||
4′/6′ | 8.09, m | 1.88, d, 1.3, 3H | 7.53, m | 7.49, d, 7.8, 2H | ||||||
5′ | 7.66, m | 2.13, d, 1.3, 3H | 7.67, m | 7.56, t, 7.8 |
δC [ppm] | ||||||||||
---|---|---|---|---|---|---|---|---|---|---|
Pos. | 1 a | 2 b | 6 b | 7 b | 9 b | 16 b | 17 b | 18 b | 19 a | 20 a |
1 | 199.4, Cq | 38.4, CH2 | 38.4, CH2 | 32.0, CH2 | 37.9, CH2 | 45.8, CH2 | 26.6, CH2 | 45.7, CH2 | 37.5, CH2 | 38.3, CH2 |
2 | 47.4, CH2 | 23.9, CH2 | 22.4, CH2 | 21.8, CH2 | 23.8, CH2 | 72.0, CH | 21.9, CH2 | 71.5, CH | 24.8, CH2 | 23.7, CH2 |
3 | 36.4, Cq | 67.4, CH | 73.6, CH | 60.1, CH | 66.9, CH | 54.2, CH | 60.2, CH | 55.1, CH | 64.8, CH | 65.2, CH |
4 | 51.4, CH | 33.9, CH2 | 28.7, CH2 | 72.9, CH | 29.9, CH2 | 76.4, CH | 73.5, CH | 75.8, CH | 30.1, CH2 | 34.8, CH2 |
5 | 165.1, Cq | 139.5, Cq | 46.8, CH | 45.9, CH | 46.3, CH | 51.6, CH | 77.8, Cq | 51.4, CH | 45.7, CH | 141.3, Cq |
6 | 125.3, CH | 124.8, CH | 29.6, CH2 | 25.1, CH2 | 29.6, CH2 | 27.0, CH2 | 21.8, CH2 | 27.0, CH2 | 28.9, CH2 | 121.4, CH |
7 | 27.2, CH2 | 32.8, CH2 | 32.8, CH2 | 32.1, CH2 | 33.0, CH2 | 33.2, CH2 | 28.6, CH2 | 33.3, CH2 | 32.0, CH2 | 32.2, CH2 |
8 | 33.4, CH2 | 32.9, CH | 36.5, CH | 36.0, CH | 36.6, CH | 36.1, CH | 35.2, CH | 36.1, CH | 35.8, CH | 32.0, CH |
9 | 60.3, CH | 51.1, CH | 54.9, CH | 55.0, CH | 55.2, CH | 57.6, CH | 46.0, CH | 57.5, CH | 54.4, CH | 50.4, CH |
10 | 12.9, CH3 | 37.7, Cq | 36.3, Cq | 38.9, Cq | 36.7, Cq | 36.1, Cq | 42.3, Cq | 36.1, Cq | 35.9, Cq | 37.0, Cq |
11 | 29.0, CH3 | 21.9, CH2 | 22.1, CH2 | 21.8, CH2 | 22.3, CH2 | 21.5, CH2 | 26.1, CH2 | 21.5, CH2 | 21.3, CH2 | 21.1, CH2 |
12 | 27.3, CH3 | 40.1, CH2 | 40.4, CH2 | 40.3, CH2 | 40.0, CH2 | 40.4, CH2 | 40.4, CH2 | 40.4, CH2 | 39.0, CH2 | 38.8, CH2 |
13 | 24.7, CH3 | 43.8, Cq | 44.0, Cq | 44.2, Cq | 45.3, Cq | 44.3, Cq | 44.2, Cq | 44.3, Cq | 44.1, Cq | 43.9, Cq |
14 | 40.4, CH3 | 57.5, CH | 57.2, CH | 57.2, CH | 57.7, CH | 57.3, CH | 57.0, CH | 57.3, CH | 56.0, CH | 56.3, CH |
15 | 25.2, CH2 | 25.1, CH2 | 23.6, CH2 | 25.4, CH2 | 25.2, CH2 | 25.0, CH2 | 25.2, CH2 | 24.3, CH2 | 24.4, CH2 | |
16 | 27.2, CH2 | 27.2, CH2 | 26.7, CH2 | 23.6, CH2 | 26.8, CH2 | 26.8, CH2 | 26.8, CH2 | 23.2, CH2 | 23.2, CH2 | |
17 | 54.1, CH | 54.2, CH | 53.1, CH | 64.7, CH | 53.1, CH | 53.1, CH | 53.2, CH | 57.0, CH | 56.9, CH | |
18 | 12.2, CH3 | 12.4, CH3 | 12.5, CH3 | 13.8, CH3 | 12.5, CH3 | 12.5, CH3 | 12.5, CH3 | 13.5, CH3 | 13.3, CH3 | |
19 | 19.5, CH3 | 12.5, CH3 | 13.0, CH3 | 12.5 CH3 | 17.4, CH3 | 15.9, CH3 | 17.3, CH3 | 12.5, CH3 | 19.6, CH3 | |
20 | 59.7, CH | 59.7, CH | 67.0, CH | 212.3, Cq | 67.1, CH | 67.0, CH | 67.1, CH | 158.9, Cq | 158.8, Cq | |
21 | 15.9, CH3 | 15.9, CH3 | 12.0, CH3 | 31.6, CH3 | 11.9, CH3 | 12.0, CH3 | 12.0, CH3 | 15.2, CH3 | 15.2, CH3 | |
22 | 29.5, CH3 | 29.5, CH3 | 43.4, CH3 | 43.4, CH3 | 43.4, CH3 | 43.4, CH3 | ||||
23 | 35.8, CH3 | 35.8, CH3 | 35.8, CH3 | 35.8, CH3 | ||||||
24 | 40.5, CH3 | 47.6, CH3 | 33.2, CH3 | 40.4, CH3 | 33.5, CH3 | 40.9, CH3 | 40.4, CH3 | |||
25 | ||||||||||
1′ | 69.3, CH2 | 166.9, Cq | 162.2, Cq | 167.1, Cq | 169.6, Cq | |||||
2′ | 130.5, Cq | 119.7, CH | 130.7, Cq | 135.7, Cq | ||||||
3′/7′ | 129.8, CH | 139.7, Cq | 131.2, CH | 129.6, CH | ||||||
4′/6′ | 130.9, CH | 27.2, CH3 | 129.7, CH | 132.8, CH | ||||||
5′ | 134.9, CH | 20.0, CH3 | 134.94, CH | 128.30, CH |
Compound | Pf [µg/mL] | Tbr [µg/mL] | Cytotox [µg/mL] | SI (Pf) | SI(Tbr) |
---|---|---|---|---|---|
1 | 0.93 ± 0.07 (3.91 µM) | 6.2 ± 0.9 (26.2 µM) | 47 ± 1 (198 µM) | 51 | 8 |
2 b | 0.898 ± 0.002 (1.53 µM) | 1.9 ± 0.2 (3.2 µM) | 19 ± 5 (33 µM) | 21 | 10 |
3 b | 0.85 ± 0.03 (1.44 µM) | 2.0 ± 0.2 (3.5 µM) | 18 ± 3 (30 µM) | 21 | 7 |
4 b | 2.3 ± 0.2 (3.4 µM) | 1.6 ± 0.5 (2.4 µM) | 5.2 ± 0.3 (7.7 µM) | 2 | 3 |
5 b | 0.91 ± 0.02 (1.34 µM) | 1.93 ± 0.06 (2.85 µM) | 5.8 ± 0.4 (8.6 µM) | 6 | 3 |
6 b | 0.25 ± 0.03 (0.39 µM) | 1.2 ± 0.4 (1.9 µM) | 87 ± 13 (136 µM) | 346 | 74 |
7 b | 0.45 ± 0.09 (0.63 µM) | 0.079 ± 0.001 (0.112 µM) | 10 ± 4 (15 µM) | 23 | 133 |
8 b | 1.82 ± 0.06 (3.09 µM) | 0.8 ± 0.1 (1.3 µM) | 10.4 ± 0.8 (17.7 µM) | 6 | 13 |
9 a | 8 ± 2 (18 µM) | 2.21 ± 0.06 (4.80 µM) | 6 ± 2 (14 µM) | 0.8 | 3 |
10 b | 0.66 ± 0.13 (0.97 µM) | 0.69 ± 0.03 (1.01 µM) | 6.5 ± 0.7 (9.5 µM) | 10 | 9 |
11 a | 3 ± 1 (7 µM) | 5.9 ± 0.3 (12.4 µM) | 28 ± 13 (60 µM) | 8 | 5 |
12 b | 2.5 ± 0.3 (4.1 µM) | 2.3 ± 0.2 (3.9 µM) | 7 ± 2 (11 µM) | 3 | 3 |
13 b | 4.6 ± 0.7 (7.7 µM) | 2.6 ± 0.4 (4.3 µM) | 11 ± 3 (18 µM) | 2 | 4 |
14 a | 18 ± 1 (36 µM) | 2.14 ± 0.05 (4.14 µM) | 12 ± 3 (23 µM) | 0.6 | 5 |
15 a | 3 ± 1 (6 µM) | 2.21 ± 0.04 (3.83 µM) | 7.3 ± 0.7 (12.7 µM) | 2 | 3 |
16 a | 6.1 ± 0.5 (10.6 µM) | 8.1 ± 0.6 (14.1 µM) | 45 ± 1 (79 µM) | 7 | 6 |
17 b | 1.6 ± 0.4 (2.3 µM) | 3 ± 2 (5 µM) | 12 ± 1 (16 µM) | 7 | 3 |
18 a | 47 ± 7 (80 µM) | 5.9 ± 0.4 (9.9 µM) | 17 ± 2 (28 µM) | 0.4 | 3 |
19 c + 20 c | 2.38 ± 0.11 (6.61 µM) | 2.71 ± 0.67 (7.52 µM) | 14.51 ± 0.31 (40.27 µM) | 6 | 5 |
Trifluoroacetate | >100 | >100 | >100 | - | - |
Chloroquine | 0.002 ± 0.000 | ||||
Melarsoprol | 0.007 ± 0.002 | ||||
Podophyllotoxin | 0.009 |
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Schäfer, L.; Cal, M.; Kaiser, M.; Mäser, P.; Schmidt, T.J. Antiprotozoal Aminosteroids from Pachysandra terminalis. Molecules 2025, 30, 1093. https://doi.org/10.3390/molecules30051093
Schäfer L, Cal M, Kaiser M, Mäser P, Schmidt TJ. Antiprotozoal Aminosteroids from Pachysandra terminalis. Molecules. 2025; 30(5):1093. https://doi.org/10.3390/molecules30051093
Chicago/Turabian StyleSchäfer, Lizanne, Monica Cal, Marcel Kaiser, Pascal Mäser, and Thomas J. Schmidt. 2025. "Antiprotozoal Aminosteroids from Pachysandra terminalis" Molecules 30, no. 5: 1093. https://doi.org/10.3390/molecules30051093
APA StyleSchäfer, L., Cal, M., Kaiser, M., Mäser, P., & Schmidt, T. J. (2025). Antiprotozoal Aminosteroids from Pachysandra terminalis. Molecules, 30(5), 1093. https://doi.org/10.3390/molecules30051093