Table 1.
In vitro activity of Aspidosperma olivaceum extracts and fractions against P. falciparum chloroquine-resistant blood parasites (W2 clone), cytotoxicity (MDL 50 ) to a human hepatoma cell line (HepG2), and selectivity index (SI), the ratio between the MDL 50 and IC 50
| Compound* | MDL 50 (μg/mL) |
IC
50
(μg/mL)** |
SI*** | |
|---|---|---|---|---|
| [ 3 H]-hypoxanthine | Anti-HRPII | |||
|
Bark extract and fractions | ||||
| Crude bark extract |
177 ± 4.0 |
10.6 ± 3.0 |
9.9 ± 4.5 |
17 |
| Acid fraction |
330 ± 54.0 |
6.4 ± 2.3 |
5.5 ± 2.5 |
52 |
| Neutral fraction |
20 ± 3.0 |
2.0 ± 0.2 |
2.1 ± 0.5 |
10 |
| Basic fraction |
27 ± 0.0 |
4.3 ± 2.5 |
3.8 ± 0.4 |
<6 |
| Neutral precipitate (NP) |
455 ± 100.0 |
6.7 ± 3.3 |
5.0 ± 2.5 |
68 |
|
Leaf extract and fractions |
|
|
|
|
| Crude leaf extract |
904 ± 135.4 |
7.2 ± 2.3 |
9.2 ± 5.4 |
126 |
| Basic residue |
415 ± 98.8 |
4.5 ± 0.7 |
2.0 ± 1.5 |
92 |
| Acid fraction |
441 ± 59.0 |
8.5 ± 3.5 |
5.3 ± 1.1 |
52 |
|
Pure substance from extracts* |
|
|
|
|
|
(1) Aspidoscarpine # |
301 ± 24.0 |
5.4 ± 2.5 |
4.4 ± 0.8 |
56 |
|
(2) Uleine |
52 ± 10.0 |
7.0 ± 0.0 |
3.2 ± 1.8 |
18 |
|
(3) Apparacine |
41 ± 2.8 |
3.0 ± 1.4 |
3.2 ± 2.7 |
14 |
| (5 N-methyl-tetrahydrolivacine | 126 ± 6.0 | 5.7 ± 3.3 | 4.0 ± 2.8 | 22 |
*The steps for the bio-fractionation of the extracts are summarized in Figure 1.
**IC50 = dose inhibiting 50% of parasite growth, evaluated in three or four different experiments for each test.
***SI = values obtained using the [3H]-hypoxanthine test; toxicity considered present at an SI <10.
#Compound (1) was isolated from the leaves and bark. The compounds are numbered 1, 2, 3, and 5 as in Figure 2; their complete names and structures are listed in Figure 1.