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Sontochin as a Guide to the Development of Drugs against Chloroquine-Resistant Malaria
- Publication Year :
- 2012
- Publisher :
- American Society for Microbiology, 2012.
-
Abstract
- Sontochin was the original chloroquine replacement drug, arising from research by Hans Andersag 2 years after chloroquine (known as “resochin” at the time) had been shelved due to the mistaken perception that it was too toxic for human use. We were surprised to find that sontochin, i.e., 3-methyl-chloroquine, retains significant activity against chloroquine-resistant strains of Plasmodium falciparum in vitro . We prepared derivatives of sontochin, “pharmachins,” with alkyl or aryl substituents at the 3 position and with alterations to the 4-position side chain to enhance activity against drug-resistant strains. Modified with an aryl substituent in the 3 position of the 7-chloro-quinoline ring, Pharmachin 203 (PH-203) exhibits low-nanomolar 50% inhibitory concentrations (IC 50 s) against drug-sensitive and multidrug-resistant strains and in vivo efficacy against patent infections of Plasmodium yoelii in mice that is superior to chloroquine. Our findings suggest that novel 3-position aryl pharmachin derivatives have the potential for use in treating drug resistant malaria.
- Subjects :
- Drug
media_common.quotation_subject
Plasmodium falciparum
Drug Resistance
Drug resistance
Biology
Pharmacology
chemistry.chemical_compound
Antimalarials
Inhibitory Concentration 50
Mice
In vivo
Chloroquine
medicine
Animals
Pharmacology (medical)
Experimental Therapeutics
media_common
Molecular Structure
Aryl
Plasmodium yoelii
medicine.disease
biology.organism_classification
Malaria
Infectious Diseases
chemistry
medicine.drug
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....619cc98b02e9530308769049983bcff7