Science (American Association for the Advancement of Science), 2010-09, Vol.329 (5996), p.1175-1180
- Rottmann, Matthias
- McNamara, Case
- Yeung, Bryan K.S
- Lee, Marcus C.S
- Zou, Bin
- Russell, Bruce
- Seitz, Patrick
- Plouffe, David M
- Dharia, Neekesh V
- Tan, Jocelyn
- Cohen, Steven B
- Spencer, Kathryn R
- González-Páez, Gonzalo E
- Lakshminarayana, Suresh B
- Goh, Anne
- Suwanarusk, Rossarin
- Jegla, Timothy
- Schmitt, Esther K
- Beck, Hans-Peter
- Brun, Reto
- Nosten, Francois
- Renia, Laurent
- Dartois, Veronique
- Keller, Thomas H
- Fidock, David A
- Winzeler, Elizabeth A
- Diagana, Thierry T
2010
Details
- Autor(en) / Beteiligte
- Rottmann, Matthias
- McNamara, Case
- Yeung, Bryan K.S
- Lee, Marcus C.S
- Zou, Bin
- Russell, Bruce
- Seitz, Patrick
- Plouffe, David M
- Dharia, Neekesh V
- Tan, Jocelyn
- Cohen, Steven B
- Spencer, Kathryn R
- González-Páez, Gonzalo E
- Lakshminarayana, Suresh B
- Goh, Anne
- Suwanarusk, Rossarin
- Jegla, Timothy
- Schmitt, Esther K
- Beck, Hans-Peter
- Brun, Reto
- Nosten, Francois
- Renia, Laurent
- Dartois, Veronique
- Keller, Thomas H
- Fidock, David A
- Winzeler, Elizabeth A
- Diagana, Thierry T
- Titel
- Spiroindolones, a Potent Compound Class for the Treatment of Malaria
- Ist Teil von
- Science (American Association for the Advancement of Science), 2010-09, Vol.329 (5996), p.1175-1180
- Ort / Verlag
- Washington, DC: American Association for the Advancement of Science
- Erscheinungsjahr
- 2010
- Link zum Volltext
- Quelle
- American Association for the Advancement of Science
- Beschreibungen/Notizen
- Recent reports of increased tolerance to artemisinin derivatives--the most recently adopted class of antimalarials--have prompted a need for new treatments. The spirotetrahydro-β-carbolines, or spiroindolones, are potent drugs that kill the blood stages of Plasmodium falciparum and Plasmodium vivax clinical isolates at low nanomolar concentration. Spiroindolones rapidly inhibit protein synthesis in P. falciparum, an effect that is ablated in parasites bearing nonsynonymous mutations in the gene encoding the P-type cation-transporter ATPase4 (PfATP4). The optimized spiroindolone NITD609 shows pharmacokinetic properties compatible with once-daily oral dosing and has single-dose efficacy in a rodent malaria model.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0036-8075eISSN: 1095-9203DOI: 10.1126/science.1193225Titel-ID: cdi_pubmed_primary_20813948
- Format
- –
- Schlagworte
- Ablation, Adenosine triphosphatases, Adenosine Triphosphatases - antagonists & inhibitors, Adenosine Triphosphatases - chemistry, Adenosine Triphosphatases - genetics, Adenosine Triphosphatases - metabolism, Animals, Antibiotics. Antiinfectious agents. Antiparasitic agents, Antimalarials, Antimalarials - administration & dosage, Antimalarials - chemistry, Antimalarials - pharmacokinetics, Antimalarials - pharmacology, Antiparasitic agents, Artemisinins, Biological and medical sciences, Cations, Cell Line, Dosage, Drug Discovery, Drug Resistance, Drug therapy, Drugs, Encoding, Erythrocytes - parasitology, Female, Genes, Protozoan, Genetic mutation, Genomics, Human protozoal diseases, Humans, Indoles - administration & dosage, Indoles - chemistry, Indoles - pharmacokinetics, Indoles - pharmacology, Infectious diseases, Inhibitor drugs, Inhibitory concentration 50, Malaria, Malaria - drug therapy, Malaria - parasitology, Male, Medical sciences, Mice, Models, Molecular, Mutant Proteins - antagonists & inhibitors, Mutant Proteins - chemistry, Mutant Proteins - metabolism, Mutation, Mutations, Nanomaterials, Nanostructure, Parasites, Parasitic diseases, Parasitic Sensitivity Tests, Pharmacology, Pharmacology. Drug treatments, Plasmodium berghei - drug effects, Plasmodium falciparum, Plasmodium falciparum - drug effects, Plasmodium falciparum - genetics, Plasmodium falciparum - growth & development, Plasmodium vivax, Plasmodium vivax - drug effects, Plasmodium vivax - growth & development, Protein synthesis, Protein Synthesis Inhibitors - administration & dosage, Protein Synthesis Inhibitors - chemistry, Protein Synthesis Inhibitors - pharmacokinetics, Protein Synthesis Inhibitors - pharmacology, Protozoal diseases, Protozoan Proteins - biosynthesis, Protozoan Proteins - chemistry, Protozoan Proteins - genetics, Protozoan Proteins - metabolism, Rats, Rats, Wistar, Spiro Compounds - administration & dosage, Spiro Compounds - chemistry, Spiro Compounds - pharmacokinetics, Spiro Compounds - pharmacology