Spiroindolones, a Potent Compound Class for the Treatment of Malaria
Rottmann M., McNamara C., Yeung BKS., Lee MCS., Zou B., Russell B., Seitz P., Plouffe DM., Dharia NV., Tan J., Cohen SB., Spencer KR., González-Páez GE., Lakshminarayana SB., Goh A., Suwanarusk R., Jegla T., Schmitt EK., Beck H-P., Brun R., Nosten F., Renia L., Dartois V., Keller TH., Fidock DA., Winzeler EA., Diagana TT.
Antimalarial Drug Candidate Spiroindolones were discovered as promising antimalarial drug candidates through a high-throughput screening approach that should be applicable to a range of neglected infectious diseases. Rottmann et al. (p. 1175 ; see the Perspective by Wells ) present the preclinical profile for an optimized spiroindolone drug candidate, NITD609. They obtained evidence for a decrease in drug sensitivity in strains of the malaria parasite Plasmodium falciparum bearing amino acid mutations in the P-type ATPase, indicating possible mechanisms of action and/or resistance.