Background
Methods
Plant material, extraction and phytochemical studies
Anti-malarial activity
In vitro growth inhibition of Plasmodium falciparum (W2 and 3D7) by the microscopic method
In vitro growth inhibition of Plasmodium falciparum (W2 and 3D7) by [3H]-hypoxanthine incorporation
In vitro growth inhibition of Plasmodium falciparum (W2) by HRPII method
Cytotoxicity assays
Results
Phytochemical studies
Compounds | Peak number | Rt (min) UPLC-ESI-MS | UV λmax (nm) UPLC-DAD | [M+H]+
UPLC-ESI-MS (m/z) | HRMS HPLC-ESI- MICROTOF-MS (m/z) | UPLC-ESI-MS/MS fragments (m/z) |
---|---|---|---|---|---|---|
Spegazzinidine | 1 | 2.06 | 317.13 | 373.43 | 373.11, 354.90, 341.10, 323.90, 311.42, 295.0, 279.10, 247.79, 231.91, 205.95, 183.71, 124.07, 108.86 | |
1,13-Dihydro-13- hydroxyuleine | 2 | 2.26 | 316.13 | 285.36 | 285.1949 | 285.11, 254.11, 238.10, 236.29, 210.16, 208.0, 206.01, 197.97, 195.15, 182.15, 168.15, 167.02, 155.96, 144.02, 130.02, 124.07, 121.89 |
Aspidocarpine | 3 | 2.50 | 304.13 | 371.40 | 371.1975 | 371.22, 353.95, 339.21, 321.0, 270.22, 249.68, 245.90, 227.69, 220.13, 199.71, 173.75, 154.10, 152.08, 142.88, 107.97 |
Deacetylaspidospermine | 4 | 2.60 | 317.13 | 313.38 | 313.1953 | 313.08, 251.89, 222.09, 206.08, 180.12, 168.03, 151.96, 140.05, 131.92 |
Pyrifolidine | 5 | 2.62 | 317.13 | 385.45 | – | 385.14, 367.12, 353.07, 327.11, 309.09, 256.10, 231.97, 167.89, 121.07 |
1-Methyldeacetyl-aspidospermidine | 6 | 2.88 | 310.13 | 327.37 | 327.2061 | 327.01, 309.16, 296.15, 283.14, 278.30, 252.21, 236.19, 197.97, 170.0, 168.24, 130.72, 129.21 |
Dasycarpidone | 7 | 2.74 | 319.13 | 269.35 | 269.1628 | 238.16, 210.12, 209.04, 192.16, 182.11, 167.06, 130.01 |
Aspidospermidin-19-ol | 8 | 3.25 | 302.13 | 299.40 | 299.1806 | 299.15, 252.02, 234.75, 233.75, 221.33, 208.10, 206.34, 196.07, 169.16, 159.39, 150.07, 138.03, 122.97, 109.17 |
N-Acetylaspidospermidine | 9 | 3.27 | 303.13 | 341.35 | 341.1856 | 341.15, 322.96, 309.17, 304.58, 295.20, 294.07, 281.29, 266.8, 251.90, 236.22, 223.01, 183.73, 168.12, 121.86, 107.82 |
Des-N-methyluleine | 10 | 3.35 | 304.13 | 253.34 | 253.1686 | 236.10, 221.10, 208.09, 207.16, 206.03, 194.09, 193.03, 182.03, 181.03, 167.02 |
Apparicine | 11 | 3.39 | 303.13 | 265.36 | 265.1678 | 265.11, 250.02, 236.12, 222.16, 208.14, 207.20, 206.09, 194.12, 180.0, 158.03, 134.01, 108.17 |
Uleine | 12 | 3.49 | 303.13 | 267.39 | 267.1845 | 236.10, 221.04, 208.09, 207.09, 206.16, 193.03, 182.09, 167.02 |
Epi-uleine | 13 | 3.53 | 304.13 | 267.69 | 267.1853 | 236.16, 221.04, 208.09, 207.03, 206.03, 194.03, 193.03, 182.03, 181.03, 167.02 |
Aspidospermine | 14 | 3.63 | 297.13 | 355.46 | 355.1993 | 355.14, 323.30, 313.08, 268.19, 256.22, 218.07, 173.81, 164.17, 124.01, 122.05 |
Dasycarpidol | 15 | 3.88 | 304.13 | 283.40 | 283.1793 | 236.23, 221.04, 208.09, 207.09, 206.16, 193.09, 192.15, 181.50, 167.0 |
Dasycarpidan | 16 | 5.51 | 303.13 | 281.30 | - | 281.05, 236.07, 222.08, 194.04 |
Anti-malarial activity
Extract/fractions/compounds | IC50 (µg/mL) P. falciparum W2 | IC50 (µg/mL) P. falciparum 3D7 | |||
---|---|---|---|---|---|
MM | HM | HRPII | MM | HM | |
Choroquine | 0.02 ± 0.002 | 0.018 ± 0.0005 | 0,0856 ± 0.0201 | 0.0013 ± 0.0001 | 0.002 ± 0.0004 |
Mefloquine | 0.016 ± 0.002 | 0.044 ± 0.008 | ND | 0.048 ± 0.0007 | 0.052 ± 0.0006 |
EEAP | 32.75 ± 1.06 | 42.51 ± 6.33 | 10,11 ± 2,22 | 20.51 ± 0.70 | 38.20 ± 0.33 |
EEAPA | 0.98 ± 0.20 | 8.0 ± 1.19 | 0.43 ± 0.11 | 7.63 ± 0.31 | 43.05 ± 4.30 |
EEAPN | 15.02 ± 2.83 | 38.02 ± 3.76 | 9,71 ± 2,63 | 17.75 ± 0.35 | 18.2 ± 1.75 |
Uleine | 0.75 ± 0.10 | 8.78a
| 2.95 ± 1.47 | 11.90 ± 0.10 | ND |
Apparicineb
| 3.0 ± 1.4 | 3.2 ± 2.7 | |||
Aspidocarpineb
| 5.4 ± 2.5 | 4.4 ± 0.8 | |||
Ellipticinec
| 0.018 |
Citotoxicity and selectivity index (SI)
Extract/fractions/compounds | Vero cells | HepG2 cells | ||||
---|---|---|---|---|---|---|
CC50 (µg/mL) | SI W2 | SI 3D7 | CC50 (µg/mL) | SI W2 | SI 3D7 | |
EEAP | >500 | >15.3 | >24.4 | >1000 | 30.5 | 48.7 |
EEAPA | 299.7 | 305.8 | 39.3 | 74.4 | 75.9 | 9.7 |
EEAPN | 449.3 | 29.9 | 25.3 | 251.0 | 16.7 | 14.1 |
Uleine | 374.6 | 499.5 | 31.5 | 301.2 | 407.6 | 25.3 |
Chloroquine | ND | ND | Nd | 185.0 | 9250.0 | 142,307.7 |