Publication: Targeting of hematin by the antimalarial pyronaridine
1
Issued Date
2006-06-01
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ISSN
00664804
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2-s2.0-33744466289
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Mahidol University
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SCOPUS
Bibliographic Citation
Antimicrobial Agents and Chemotherapy. Vol.50, No.6 (2006), 2197-2200
Suggested Citation
Saranya Auparakkitanon, Soebsakul Chapoomram, Kannika Kuaha, Thamrong Chirachariyavej, Prapon Wilairat Targeting of hematin by the antimalarial pyronaridine. Antimicrobial Agents and Chemotherapy. Vol.50, No.6 (2006), 2197-2200. doi:10.1128/AAC.00119-06 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/23738
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Title
Targeting of hematin by the antimalarial pyronaridine
Abstract
Pyronaridine, 2-methoxy-7-chloro-10[3′,5′-bis(pyrrolidinyl-1- methyl-)4′hydroxyphenyl]aminobenzyl-(b)-1,5-naphthyridine, a new Mannich base schizontocide originally developed in China and structurally related to the aminoacridine drug quinacrine, is currently undergoing clinical testing. We now show that pyronaridine targets hematin, as demonstrated by its ability to inhibit in vitro β-hematin formation (at a concentration equal to that of chloroquine), to form a complex with hematin with a stoichiometry of 1:2, to enhance hematin-induced red blood cell lysis (but at 1/100 of the chloroquine concentration), and to inhibit glutathione-dependent degradation of hematin. Our observations that pyronaridine exerted this mechanism of action in situ, based on growth studies of Plasmodium falciparum K1 in culture showing antagonism of pyronaridine in combination with antimalarials (chloroquine, mefloquine, and quinine) that inhibit β-hematin formation, were equivocal. Copyright © 2006, American Society for Microbiology. All Rights Reserved.