Synthesis and in vitro and in vivo evaluation of antimalarial polyamines
| Autor: | Brent R. Copp, A. Norrie Pearce, Marcel Kaiser, Lydia P. Liew |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Pharmacology
Natural product Dose-Response Relationship Drug Molecular Structure biology Plasmodium falciparum Organic Chemistry Spermine General Medicine biology.organism_classification Antimalarials Structure-Activity Relationship chemistry.chemical_compound Parasitic Sensitivity Tests chemistry In vivo parasitic diseases Drug Discovery Polyamines Structure–activity relationship Plasmodium berghei Benzamide Polyamine |
| Zdroj: | European Journal of Medicinal Chemistry. 69:22-31 |
| ISSN: | 0223-5234 |
| Popis: | We recently reported that 1,14-diphenylacetamide derivatives of spermine exhibit potent nM in vitro growth inhibition properties of Plasmodium falciparum. In an effort to expand the structure-activity relationship of this compound class towards malaria, we have prepared and biologically tested a library that includes benzamide and 3-phenylpropanamide 'capping acid' groups, and polyamines that include spermine (PA3-4-3) and chain extended analogues PA3-8-3 and PA3-12-3. 2-Hydroxy and 2,5-dimethoxy analogues were typically found to exhibit the most potent activity towards the dual drug resistant strain K1 of P. falciparum with IC50's in the range of 1.3-9.5 nM, and selectivity indices (SI) of 42,300 to 4880. In vivo evaluation of three analogues against Plasmodium berghei was undertaken, with one demonstrating a modest 27.9% reduction in parasitaemia. |
| Databáze: | OpenAIRE |
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