Antischistosomal drugs: Past, present … and future?

The schistosome enzyme that activates oxamniquine has the characteristics of a sulfotransferase

“…This study contributes additional evidence to the available information regarding the proposed mechanism of action of OXA (Cioli et al 1995). It was previously shown that an enzymatic activity present in OXA-sensitive schistosomes (but absent in drug resistant worms) could produce the covalent binding of OXA to the DNA and other macromolecules of the parasite .…”

“…It was previously shown that an enzymatic activity present in OXA-sensitive schistosomes (but absent in drug resistant worms) could produce the covalent binding of OXA to the DNA and other macromolecules of the parasite . It was postulated that the schistosome enzyme was inducing the formation of an OXA ester that would then spontaneously dissociate giving rise to an electrophilic moiety capable of alkylating parasite macromolecules (Cioli et al 1985(Cioli et al , 1995. The chemical nature of the postulated ester was, however, unknown and a direct identification was problematic in view of the very short half life that such an unstable compound would exhibit.…”

“…The procedure effectively eliminates free tritiated OXA (soluble in organic solvents), while allowing the estimation of macromolecule-bound radioactivity remaining in the aqueous phase . Early experiments of this study were carried out using hycanthone, but it was later shown that OXA and hycanthone have an identical mechanism of action (Cioli et al 1995), and most of the later experiments were carried out using OXA. When hycanthone was used, this is indicated in the text.…”

“…Available information on the mechanism of action of OXA (and of the related agent hycanthone) suggests that the drug becomes active only upon transformation to an alkylating agent by an enzyme that is present in OXA-sensitive schistosomes (reviewed in Cioli et al 1995). The evidence originates from genetic crosses between OXA-sensitive and OXAresistant S. mansoni showing that resistance is a recessive trait, thus implying the existence of a parasite factor that is required for drug activity .…”

Un nouvel espoir dans le traitement de la schistosomiase

“…Au cours du XX e siècle, de nombreuses drogues allant de molécules très toxiques (comme les dérivés de l'antimoine) à des composés chimiques mieux tolérés (niridazole, hycanthone, oxamniquine, metrifonate, oltipraz…) ont été utilisées tour à tour pour le traitement de la schistosomiase [2]. Depuis ces trente dernières années, la drogue la plus largement utilisée est le Praziquantel (Biltricide ® ) car elle présente de nombreux avantages.…”