Novel frontiers through nitrogen substitution at 6th, 10th and 11th position of artemisinin: Synthetic approaches and antimalarial activity

Abstract

Malaria pertains to an array of catastrophic illnesses spurred on by the Plasmodium spp. Artemisinin (ART) is currently prescribed in conjunction with another medication as part of therapeutic regimens for acute malaria. These currently prescribed pharmaceuticals have been around for a while, even after lack of required thermos-metabolic stabilities, alongside fresh proclaims about surfacing resistance and neurotoxicity linked with sequential administration of such combination therapies. Over the years, ARTs seem to have gained popularity through the accelerated reduction in parasitaemia, thus dictating use of differentially stable ART derivatives, in combination or alone, to control the proliferation of malaria. The endoperoxide bridge in the ART pharmacophore plays a non-negotiable role in its action against multiple stages in the parasitic life cycle. However, shorter half-lives and limited bioavailability tend to open doors for another class of endoperoxides. Nitrogen substitution at 6th, 10th and 11th positions of ART draws attention as the best replacements through their disparate stabilities and inability to demonstrate in vivo hydrolytic decomposition into DHA. Discussions pertaining such azaartemisinins and aminoartemisinins reported over the past 30 years have been strongly focused upon, on account of their synthetic methodologies and antimalarial efficacies, in order to assign future candidature to the meritorious moiety.