Optimisation of the allylsilane approach to C-10 deoxo carba analogues of dihydroartemisinin: synthesis and in vitro antimalarial activity of new, metabolically stable C-10 analogues

Autor:	Paul M. O'Neill, B. Kevin Park, Jill Davies, Andrew V. Stachulski, Matthew D. Pugh, Stephen A. Ward
Rok vydání:	2001
Předmět:	biology Chemistry Stereochemistry medicine.medical_treatment Dihydroartemisinin Plasmodium falciparum biology.organism_classification In vitro chemistry.chemical_compound Mechanism of action Chloroquine parasitic diseases medicine Formate Artemether medicine.symptom Artemisinin medicine.drug
Zdroj:	Journal of the Chemical Society, Perkin Transactions 1. :2682-2689
ISSN:	1364-5463 1472-7781
DOI:	10.1039/b104340b
Popis:	An optimised protocol has been developed for the coupling of dihydroartemisinin benzoate with a range of aromatic allylsilanes to provide a number of new C-10 deoxo derivatives (11a–11g) in yields ranging from 70 to 94%. These compounds were up to ten times more potent than artemisinin in in vitro tests against the chloroquine resistant K1 strain of Plasmodium falciparum. Ferrous mediated degradation of these analogues produces as the main product, a dicarbonyl formate 12, which is not seen when the same reaction is carried out with artemisinin or artemether. This finding may indicate that analogues in this class have a subtly different “antimalarial” mechanism of action.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_________::90fb9bd80ceb1e9431c1f2ca78799321 https://doi.org/10.1039/b104340b Zobrazit plný text záznamu