Table 1.
In vitro activity of compounds 1–13 against T. b. rhodesiense (STIB 900), L. donovani (MHOM-ET-67/L82) axenic and intracellular amastigotes, P. falciparum (NF54), and cytotoxicity in L6 cells and intramacrophages.
| IC50 a (µM) | |||||||
|---|---|---|---|---|---|---|---|
| No. | Compound | L. donovani | T. b. rhodesiense | P. falciparum | L6 cells | Cytotoxicity | |
| Axenic | Intramacrophage | Intramacrophage | |||||
| 1 | Quercetin-3,3′,4′-trimethylether | 18.8 ± 4.0 (9.8)b | >79.9 | 55.1 ± 13.2 (3.4)b | 42.1 ± 12.5 (4.4)b | 185.2 ± 15.4 | 154.5 ± 19.3 |
| 2 | Ayanin | 8.2 ± 1.6 (12.2)b | >95.9 | 11.2 ± 0.2 (8.9)b | 7.8 ± 0.9 (12.9)b | 100.3 ± 9.3 | 127.9 ± 3.5 |
| 3 | Retusin | 34.1 ± 4.7 (6.3)b | >185.8 | 83.8 ± 7.5 (2.6)b | 23.4 ± 3.8 (9.2)b | 215.1 ± 4.7 | 173.2 ± 0.0 |
| 4 | Naringenin | 41.8 ± 9.3 (5.6)b | >121.3 | 184.2 ± 9.9 (1.3)b | 73.2 ± 5.9 (3.2)b | 233.3 ± 36.9 | 332.9 ± 18.2 |
| 5 | Quercetin-3,4′-dimethylether | 15.2 ± 3.1 (1.3)b | >33.3 | 6.6 ± 3.2 (2.9)b | 18.2 ± 6.7 (1.1)b | 19.2 ± 1.0 | 42.7 ± 12.1 |
| 6 | Quercetin-3,7-dimethylether | 4.5 ± 0.3 (12.3)b | >66.7 | 2.4 ± 0.5 (23.2)b | 7.3 ± 0.6 (7.6)b | 55.4 ± 34.3 | 101.5 ± 49.7 |
| 7 | 3-Methoxy-4-hydroxybenzoic acid | 153.3 ± 45.5 (3.9)b | >595.2 | 38.6 ± 5.9 (15.4)b | 138.4 ± 12.2 (4.3)b | 595.2 ± 0.0 | >500 |
| 8 | Laudanine | 193.3 ± 0.0 (1.5)b | >291.5 | 143.1 ± 0.0 (2.0)b | 78.6 ± 0.4 (3.7)b | 291.5 ± 0.0 | >200 |
| 9 | Laudanosine | 185.4 ± 0.0 (1.5)b | >186.3 | 101.5 ± 38.8 (2.8)b | 76.1 ± 21.6 (3.7)b | 280.1 ± 0.0 | >245 |
| 10 | Pinoresinol | 151.4 ± 22.6 (1.6)b | >279.3 | 116.8 ± 0.3 (2.1)b | >139.7 | 241.9 ± 21.2 | >270 |
| 11 | Isorhamnetin | 21.7 ± 7.9 (6.0)b | >210.4 | 25.9 ± 5.4 (5.0)b | 21.6 ± 0.7 (6.0)b | 130.2 ± 58.7 | >198.9 |
| 12 | Pseudosemiglabrin | 18.9 ± 2.6 (4.1)b | >84.2 | 37.5 ± 6.1 (2.1)b | 16.3 ± 2.7 (4.8)b | 78.1 ± 29.8 | 144.6 ± 10.5 |
| 13 | Kaempferol | 20.8 ± 1.7 (5.3)b | >115.4 | 36.4 ± 8.7 (3.1)b | 53.1 ± 7.7 (2.1)b | 111.4 ± 16.6 | 151.0 ± 18.8 |
| Positive control | 0.5 ± 0.2c | 6.6 ± 0.3c | 0.01 ± 0.003d | 0.01 ± 0.002e | 0.03 ± 0.005f | >24.1 | |
aThe IC50s are mean values from at least two independent replicates ± absolute deviation.
bSelectivity index (SI): IC50 in L6 cells divided by IC50 in the titled parasitic strain.
cMiltefosine, dMelarsoprol, eChloroquine fPodophyllotoxin.