US EPA

1182513 

Journal Article 

Central role of hemoglobin degradation in mechanisms of action of 4-aminoquinolines, quinoline methanols, and phenanthrene methanols 

Mungthin, M; Bray, PG; Ridley, RG; Ward, SA 

1998 

Yes 

Antimicrobial Agents and Chemotherapy
ISSN: 0066-4804
EISSN: 1098-6596 

AMER SOC MICROBIOLOGY 

WASHINGTON 

42 

11 

2973-2977 

English 

9797235 

10.1128/AAC.42.11.2973 

WOS:000076692500033 

https://AAC.asm.org/content/42/11/2973
Exit
 

We have used a specific inhibitor of the malarial aspartic proteinase plasmepsin I and a nonspecific cysteine proteinase inhibitor to investigate the importance of hemoglobin degradation in the mechanism of action of chloroquine, amodiaquine, quinine, mefloquine (MQ), halofantrine, and primaquine. Both proteinase inhibitors antagonized the antiparasitic activity of all drugs tested with the exception of primaquine. An inhibitor of plasmepsin I, Ro40-4388, reduced the incorporation of radiolabelled chloroquine and quinine into malarial pigment by 95%, while causing a 70% reduction in the incorporation of radiolabelled MQ. Cysteine proteinase inhibitor E64 reduced the incorporation of chloroquine and quinine into malarial pigment by 60 and 40%, respectively. This study provides definitive support for the central role of hemoglobin degradation in the mechanism of action of the 4-aminoquinolines and the quinoline and phenanthrene methanol antimalarials.