Highly Antimalaria-Active Artemisinin Derivatives: Biological Activity Does Not Correlate with Chemical Reactivity

摘要

Artemisinin (1, qinghaosu), and the derivatives dihydroartemisinin (DHA, 2), artemether (3), and artesunate (4) are the most potent and rapidly acting antimalarial drugs. Nevertheless, artemether (3) and artesunate (4) have short terminal half-lives, a consequence of facile metabolism to DHA, a highly neurotoxic compound. Therefore, there is an urgent need to develop practical routes to new derivatives that are more stable and do not undergo metabolism to DHA.