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Design, Synthesis, and Evaluation of Novel Ferroquine and Phenylequine Analogues as Potential Antiplasmodial Agents
Author(s) -
Jacobs Leon,
de Kock Carmen,
de Villiers Katherine A.,
Smith Peter J.,
Smith Vincent J.,
van Otterlo Willem A. L.,
Blackie Margaret A. L.
Publication year - 2015
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201500349
Subject(s) - hemozoin , plasmodium falciparum , chloroquine , ic50 , in vitro , chemistry , antimalarial agent , malaria , pharmacology , stereochemistry , combinatorial chemistry , biochemistry , biology , immunology
Abstract 7‐Chloroquinoline‐based antimalarial drugs are effective in the inhibition of hemozoin formation in the food vacuole of the Plasmodium parasite, the causative agent of malaria. We synthesized five series of ferroquine (FQ) and phenylequine (PQ) derivatives, which display good in vitro efficacy toward both the chloroquine‐sensitive (CQS) NF54 (IC 50 : 4.2 n m ) and chloroquine‐resistant (CQR) Dd2 (IC 50 : 33.7 n m ) strains of P. falciparum . Several compounds were found to have good inhibitory activity against β‐hematin formation in an NP‐40 detergent assay, with IC 50 values ranging between 10.4 and 19.2 μ m .