By D Sullivan, S Krishna
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2000, 2001). It is proposed that these hybrids may have the capacity to hit the parasite by two different mechanisms (namely, free radical mediated damage and interference with FP crystallization and detoxication). 6 Summary In this chapter we have attempted to describe the exciting new advances in our knowledge of the mechanism of action and parasite resistance of two of the most important groups of semisynthetic antimalarials. Clearly we have Quinolines and Artemisinin: Chemistry, Biology and History 29 come a long way since the days of traditional herbal remedies but we are up against a sophisticated foe and we must not allow the drug resistant parasites to gain the upper hand.
1995, 2001) the dispiro tetraoxanes (15, 16) (Vennerstrom et al. 2000) and the endoperoxide analogues such as arteflene (17) (Hofheinz et al. 1994) a synthetic analogue of the naturally occurring yingzhaozu A (18) (Zhou and Xu 1994). More recently, tetraoxane (19) with Quinolines and Artemisinin: Chemistry, Biology and History 27 Fig. 11 Selected second-generation artemisinin derivatives an IC50 as low as 3 nM has been discovered (artemisinin IC50 =10 nM) and analogues in this class have been shown to be effective when given orally in mice infected with P.
J Protozool 31:A82–A83 Yayon A, Cabantchik ZI, Ginsburg H (1985) Susceptibility of human malaria parasites to chloroquine is pH dependent. Proc Natl Acad Sci USA 82:2784–2788 Yayon A, Ginsburg H (1983) Chloroquine inhibits the degradation of endocytic vesicles in human malaria parasites. Cell Biol Int Rep 7:895–895 Zhang F, Gosser DK, Meshnick SR (1992) Hemin-catalyzed decomposition of artemisinin (Qinghaosu). Biochem Pharmacol 43:1805–1809 Zhang JM, Krugliak M, Ginsburg H (1999) The fate of ferriprotorphyrin IX in malaria infected erythrocytes in conjunction with the mode of action of antimalarial drugs.
