Volume 4, Number 1—March 1998
Synopsis
Proteases of Malaria Parasites: New Targets for Chemotherapy
Philip J. Rosenthal
Table 3
Protease targets for chemotherapy
| Effective inhibitorsa |
||||
|---|---|---|---|---|
| Protease | Biologic role | Compound (Reference) | In vitrob (IC50; μM) | In vivoc (mg/kg/day) |
| Pf68 | Erythrocyte invasion | GlcA-Val-Leu-Gly-Lys-NHC2H5 (40) | 900 | |
| Plasmepsin I | Hemoglobin degradation | SC-50083 (41) Ro 40-4388 (42) | 2-5 0.25 | |
| Plasmepsin II | Hemoglobin degradation | Compound 7 (43) | 20 | |
| Falcipain | Hemoglobin degradation | Z-Phe-Arg-CH2F (44) | 0.064 | |
| Mu-Phe-HPh-CH2F (45) | ~0.03 | 400 | ||
| Mu-Leu-HPh-VSPh (46) | 0.01 | |||
| Oxalic bis ((2-hydroxy-1-naph- thylmethylene)hydrazide) (47) | 7 | |||
| 1-(2,5-dichlorophenyl)-3- (4-quinolinyl)-2-propen-1-one (48) | 0.23 | |||
| 7-chloro-1,2-dihydro-2-(2,3-di- methoxy-phenyl)-5,5-dioxide- 4-(1H,10H)-phenothiazinone (49) | 2 | |||
aThe structures of these compounds and details of the described studies are in the references noted.
bAssays compared the development of new ring-form parasites or the uptake of [3H]hypoxanthine by treated and control parasites.
cCure of Plasmodium vinckei-infected mice.
