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- W1971817686 abstract "Quinoline compounds, such as chloroquine, are used widely to treat malaria; however, the malarial parasite is rapidly becoming resistant to the drugs currently available. Presently, rational drug design is hindered considerably due to the mode of action of chloroquine being poorly understood. We rely on serendipity, rather than solid structural evidence, to generate new antimalarials. Hence any insight into the possible modes of action of quinoline antimalarials, including the bisquinolines, would greatly aid rational drug design. The quinoline antimalarial drugs, chloroquine, quinine and mefloquine, are thought to act by interfering with the digestion of haemoglobin in the blood stages of the malaria life-cycle. These quinoline antimalarials traverse down the pH gradient to accumulate to millimolar concentrations in the acidic vacuole of the parasite. It has been suggested that this high intravacuolar concentration prevents haem sequestration, causing a build up of the toxic haem moiety and the death of the parasite by its own toxic waste. The actual mechanism by which the parasite sequesters haem and the drug target(s) during this process, however, still remains elusive. As a consequence, haem polymerisation and the efficiency of quinoline antimalarials, including the bisquinolines, as inhibitors of this process has been investigated. In this paper, the potential role of the bisquinolines in the fight against chloroquine-resistant malaria is addressed." @default.
- W1971817686 created "2016-06-24" @default.
- W1971817686 creator A5085824167 @default.
- W1971817686 date "1999-03-01" @default.
- W1971817686 modified "2023-09-23" @default.
- W1971817686 title "Invited review Bisquinoline antimalarials: their role in malaria chemotherapy" @default.
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- W1971817686 doi "https://doi.org/10.1016/s0020-7519(98)00217-3" @default.
- W1971817686 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/10333319" @default.
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