MEDICINES AND RELATED SUBSTANCES CONTROL …
Oxamniquine has a complicated manufacturing process, requiring big fermentation tanks for biological synthesis, resulting in a high cost, when compared to praziquantel.
Vitamin B-Complex | Michigan Medicine
Schistosomiasis is a parasitic disease that affects more than 250 million people annually, mostly children in poor, tropical, rural areas. Only one treatment (praziquantel) is available, putting control efforts at risk should resistance occur. In pursuit of treatment alternatives, we derivatized an old antischistosomal agent, oxamniquine (OXA). Four organometallic derivatives of OXA were synthesized and tested against in vitro and in vivo. Of these, a ferrocenyl derivative, 1, killed larval and adult worms 24 h postexposure in vitro, in contrast to OXA, which lacks in vitro activity against adult worms. A dose of 200 mg/kg of 1 completely eliminated the worm burden in mice. Subsequently, a ruthenocenyl (5) and a benzyl derivative (6) of OXA were synthesized to probe the importance of the ferrocenyl group in 1. Compounds 1, 5, and 6 were lethal to both and adults in vitro. In vivo, at 100 mg/kg, all three compounds revealed worm burden reductions of 76 to 93%, commensurate with OXA. Our findings present three compounds with activity against in vitro, comparable activity in vivo, and high activity against in vitro. These compounds may possess a different binding mode or mode of action compared to OXA and present excellent starting points for further SAR studies.
Oxamniquine is a semisynthetic tetrahydroquinoline and possiblyacts by binding resulting incontraction and paralysis of the worms and eventual detachment fromterminal in the mesentry and death. It isalso hypothesized that its biochemical mechanisms are related to ananticholinergic effect which increases the parasite’s motility, aswell as to synthesis inhibition of nucleic acids. Oxamniquine actsmainly on male worms but also induces small changes on a smallproportion of females. Like , it promotes more severedamage of the dorsal tegument than of the ventral surface. The drugcauses the male worms to shift from the mesenteric circulation tothe liver where the cellular host response causes its finalelimination. The changes caused in the females are reversible andare due primarily to the discontinued male stimulation rather thanthe direct effect of oxamniquine.