Abstract:
Malaria is one of the most endemic infectious diseases in developing countries.
Increase in multi-drug resistant parasite strain to currently available antimalarial drugs
make it imperative to find new and effective antimalarial drugs as well as those with
novel mechanism of action. Artemisinin (1) is clinically valuable antimalarial agent
due to its excellent antimalarial activity. The homolytic cleavage of OO bond is
believed to be the key factor for its antimalarial activity and hence many research
laboratories have focused on endoperoxide moiety, including endocyclic NO bond.
Derivatives of ethyl 5-phenyl-6-oxa-1-azabicyclo[3.1.0]hexane-2-carboxyalte
(77) have been prepared. Fe(II)-catalyzed homolytic cleavage of NO bond led to the
formation of carbon-centered radical intermediate, which is similar to the mode of
action of artemisinin. Accordingly, additional oxaziridenes (108114) have thus been
synthesized. Their in vitro activities against P. falciparum (K1 strain),
antimycobacterium and also their cytotoxic activities against vero cell have
subsequently been evaluated.