Table 2.
In Vitro Activity of the Manzamine Alkaloids against Mycobacterium tuberculosis, Malaria, and Leishmaniaa
| compound | activity in vitro
|
|||||
|---|---|---|---|---|---|---|
| M. tuberculosis (H37Rv) MIC, μg/mL | P. falciparum (D6 clone) IC50, ng/mL | P. falciparum (chlorine-resistant W2 clone) IC50, ng/mL |
L. donovani
|
cytotoxicity (Vero), μg/mL | ||
| IC50, μg/mL | IC90, μg/mL | |||||
| manzamine A (2) | 1.5 | 4.5 | 8.0 | 0.9 | 1.8 | 1.2 |
| (+)-8-hydroxymanzamine A (6) | 0.9 | 6.0 | 8.0 | 6.2 | 11 | 1.1 |
| manzamine A N-oxide (5) | 3.9 | 11 | 13 | 1.1 | 3.8 | 4.2 |
| 3,4-dihydromanzamine A-N-oxide | NT | 1600 | 3700 | NT | NT | NC |
| 12,34-oxamanamine E (3) | NT | NA | NA | NA | NA | NC |
| manzamine E (7) | 3.8 | 3400 | 4760 | 3.8 | 6.8 | NC |
| 6-hydroxymanzamine E (8) | 0.4 | 780 | 870 | 2.5 | 4.3 | 4.3 |
| manzamine F (9) | 2.6 | 780 | 1700 | 4.2 | 7.0 | NC |
| manzamine J (1) | 1.7 | 1300 | 750 | 25 | 45 | NC |
| 6-deoxymanzamine X | 1.8 | 1300 | 1400 | 3.2 | 7.5 | 4.7 |
| manzamine X | NT | 950 | 2000 | 5.7 | 11 | NC |
| neo-kauluamine | 2.0 | 1700 | 2800 | 4.2 | 8.2 | NC |
| ircinal A | 30.2 | NA | NA | 4.6 | 8.5 | NC |
| ircinol A (10) | 1.9 | 2400 | 3100 | 0.9 | 0.7 | NC |
| rifampin | 0.5 | NT | NT | NT | NT | NT |
| chloroquine | NT | 15.5 | 170 | NT | NT | NT |
| artemisinin | NT | 10 | 6.3 | NT | NT | NT |
| pentamidine | NT | NT | NT | 2.1 | 10 | NT |
| amphotercin B | NT | NT | NT | 0.06 | 0.15 | NT |
a
NA = not active (concentration 5.0 μg/mL); NT = not tested; NC = no cytotoxicity (concentration: 4.7 μg/mL).