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Antimicrobial effects of N-benzyloxycarbonyl-S-(2,4-dinitrophenyl) glutathione diesters against chloroquinine sensitive (NF54) and resistant (K1) strains of Plasmodium falciparum.
Bioorganic Chemistry 2018 August
N-Benzyloxycarbony-S-(2,4-dinitrophenyl)glutathione diesters have been investigated for antimalarial activity against chloroquinine sensitive (NF54) and resistant (K1) strains of P. falciparum. Both strains appear equally susceptible to inhibition by compounds 1-4, with an IC50 ∼ 4.92-6.97 μM, consistent with the target of these compounds being the PfMRP transporter. Against the NF54 strain, diester derivatives containing ethyl side chains showed lower in vitro activity than those with methyl side chains 1-4, IC50 ∼ 5.7-6.97 μM with the exception of compound 5 (IC50 > 25 μM). The cytotoxicity of compounds with log P ∼ 3.9-5.8 were lower against the murine L6 cell line than compounds with a higher log P > 5.8 that were toxic. Overall the cytotoxicity of compounds 1-7 were lower against KB cells than against the L6 cell line with the exception of compound 4, which showed a higher relative toxicity.
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