Figure 5: Working hypothesis for the mode of action and optimization of R.

(a) Ortho-hydroxylated arylmethyl amines exhibit the highest antimalarial activity. A chelate involving quinone methide mechanism is substantiated via structure/activity considerations. Both the redox pair phenol/quinone and the highly reactive quinone methide itself may be causative for biological activity. (b,c) The steroid core also plays a crucial role. The highest activity is found for estratriene derivatives.