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Lead optimization of antimalarial propafenone analogues.

ABSTRACT: Previously reported studies identified analogues of propafenone that had potent antimalarial activity, reduced cardiac ion channel activity, and properties that suggested the potential for clinical development for malaria. Careful examination of the bioavailability, pharmacokinetics, toxicology, and efficacy of this series of compounds using rodent models revealed orally bioavailable compounds that are nontoxic and suppress parasitemia in vivo. Although these compounds possess potential for further preclinical development, they also carry some significant challenges.

SUBMITTER: Lowes D

PROVIDER: S-EPMC4408918 | biostudies-literature | 2012 Jul

REPOSITORIES: biostudies-literature

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Lead optimization of antimalarial propafenone analogues.

Lowes David D Pradhan Anupam A Iyer Lalitha V LV Parman Toufan T Gow Jason J Zhu Fangyi F Furimsky Anna A Lemoff Andrew A Guiguemde W Armand WA Sigal Martina M Clark Julie A JA Wilson Emily E Tang Liang L Connelly Michele C MC Derisi Joseph L JL Kyle Dennis E DE Mirsalis Jon J Guy R Kiplin RK

Journal of medicinal chemistry 20120629 13

Previously reported studies identified analogues of propafenone that had potent antimalarial activity, reduced cardiac ion channel activity, and properties that suggested the potential for clinical development for malaria. Careful examination of the bioavailability, pharmacokinetics, toxicology, and efficacy of this series of compounds using rodent models revealed orally bioavailable compounds that are nontoxic and suppress parasitemia in vivo. Although these compounds possess potential for furt ...[more]

PMID: 22708838

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2018-06-20 | GSE110426 | GEO

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