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• W2073729235 abstract "The emergence and spread of malaria parasites that are resistant to chloroquine (CQ) has been a disaster for world health. The antihistamine chlorpheniramine (CP) partially resensitizes CQ-resistant (CQR) parasites to CQ but possesses little intrinsic antiplasmodial activity. Mutations in the parasite's CQ resistance transporter (PfCRT) confer resistance to CQ by enabling the protein to transport the drug away from its site of action, and it is thought that resistance-reversers such as CP exert their effect by blocking this CQ transport activity. Here, a series of new structural analogues and homologues of CP have been synthesized. We show that these compounds (along with other in vitro CQ resistance-reversers) inhibit the transport of CQ via a resistance-conferring form of PfCRT expressed in Xenopus laevis oocytes. Furthermore, the level of PfCRT-inhibition was found to correlate well with both the restoration of CQ accumulation and the level of CQ resensitization in CQR parasites." @default.
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• W2073729235 date "2014-03-24" @default.
• W2073729235 modified "2023-10-17" @default.
• W2073729235 title "Chlorpheniramine Analogues Reverse Chloroquine Resistance in <i>Plasmodium falciparum</i> by Inhibiting PfCRT" @default.
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• W2073729235 doi "https://doi.org/10.1021/ml5000228" @default.
• W2073729235 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4027738" @default.
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• W2073729235 hasPublicationYear "2014" @default.
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