Dynamic covalent bonding (DCB): the bond lability of alkoxyamines as drugs against Schistosoma mansoni and Plasmodium falciparum

Dynamic covalent bonding (DCB) has been a rising concept for the past several years in materials sciences. This article describes how the bond lability involved in DCB is applied to develop drugs against tropical parasitic diseases such as malaria and bilharziasis. Recently, we showed that some alkoxyamines (typical molecules exhibiting DCB) exhibit activities against (for A8L, 100% worm mortality in 48 hours at 10 μg ml ) and (for A8L, IC = 270 nM). Here, the combination of enzymatic-physical (solvent effect) activation or of enzymatic-chemical (acetal hydrolysis) activation is used to develop alkoxyamines that show activity against both parasites. The enzymatic step controls the specificity of the drug.