%0 Journal Article %1 Friebolin.20080313 %A Friebolin, Wolfgang %A Jannack, Beate %A Wenzel, Nicole %A Furrer, Julien %A Oeser, Thomas %A Sanchez, P. Cecilia %A Lanzer, Michael %A Yardley, Vanessa %A Becker, Katja %A Davioud-Charvet, Elisabeth %D 2008/03/13/ %J J Med Chem %K Animals Antimalarials Biological_Transport Cell_Line Combination Drug_Resistance Drug_Therapy Glutathione_Reductase Humans IFZ Inbred_BALB_C Malaria Mice Naphthalenes Parasitic_Sensitivity_Tests Plasmodium_berghei Plasmodium_falciparum Structure-Activity_Relationship Tumor chloroquine %N 5 %P 1260-1277 %T Antimalarial dual drugs based on potent inhibitors of glutathione reductase from Plasmodium falciparum %V 51 %X Plasmodium parasites are exposed to higher fluxes of reactive oxygen species and need high activities of intracellular antioxidant systems providing a steady glutathione flux. As a future generation of dual drugs, 18 naphthoquinones and phenols (or their reduced forms) containing three different linkers between the 4-aminoquinoline core and the redox active component were synthesized. Their antimalarial effects have been characterized in parasite assays using chloroquine-sensitive and -resistant strains of Plasmodium, alone or in drug combination, and in the Plasmodium berghei rodent model. In particular, two tertiary amides 34 and 36 showed potent antimalarial activity in the low nanomolar range against CQ-resistant parasites. The ability to compete both for (Fe (III))protoporphyrin and for chloroquine transporter was determined. The data are consistent with the presence of a carrier for uptake of the short chloroquine analogue 2 but not for the potent antimalarial amide 34, suggestin

@article{Friebolin.20080313, abstract = {Plasmodium parasites are exposed to higher fluxes of reactive oxygen species and need high activities of intracellular antioxidant systems providing a steady glutathione flux. As a future generation of dual drugs, 18 naphthoquinones and phenols (or their reduced forms) containing three different linkers between the 4-aminoquinoline core and the redox active component were synthesized. Their antimalarial effects have been characterized in parasite assays using chloroquine-sensitive and -resistant strains of Plasmodium, alone or in drug combination, and in the Plasmodium berghei rodent model. In particular, two tertiary amides 34 and 36 showed potent antimalarial activity in the low nanomolar range against CQ-resistant parasites. The ability to compete both for (Fe (III))protoporphyrin and for chloroquine transporter was determined. The data are consistent with the presence of a carrier for uptake of the short chloroquine analogue 2 but not for the potent antimalarial amide 34, suggestin}, added-at = {2008-10-14T16:07:18.000+0200}, author = {Friebolin, Wolfgang and Jannack, Beate and Wenzel, Nicole and Furrer, Julien and Oeser, Thomas and Sanchez, P. Cecilia and Lanzer, Michael and Yardley, Vanessa and Becker, Katja and Davioud-Charvet, Elisabeth}, biburl = {https://www.bibsonomy.org/bibtex/2b5fd6712f1a844b98b42a4084bc69b44/nutribiochem}, interhash = {74c6a4dca43d995c6afa6d380908118c}, intrahash = {b5fd6712f1a844b98b42a4084bc69b44}, issn = {0022-2623}, journal = {J Med Chem}, keywords = {Animals Antimalarials Biological_Transport Cell_Line Combination Drug_Resistance Drug_Therapy Glutathione_Reductase Humans IFZ Inbred_BALB_C Malaria Mice Naphthalenes Parasitic_Sensitivity_Tests Plasmodium_berghei Plasmodium_falciparum Structure-Activity_Relationship Tumor chloroquine}, number = 5, pages = {1260-1277}, timestamp = {2008-10-14T16:08:41.000+0200}, title = {Antimalarial dual drugs based on potent inhibitors of glutathione reductase from Plasmodium falciparum}, volume = 51, year = {2008/03/13/} }