Design, synthesis, and in vivo evaluation of oxamniquine methacrylate and acrylamide prodrugs

Oxamniquine is an antiparasitic agent commonly used in therapeutics against Schistosoma mansoni. Although it is well tolerated, some adverse effects justify the search for new compounds with prolonged biological action, so that monomeric and polymeric oxamniquine prodrugs were designed. Synthetic results assisted by molecular modeling study showed the possibility to obtain the corresponding monomeric forms of the oxamniquine methacrylate (1) and oxamniquine acrylamide (2). Successful copolymerization procedure only occurred on the methacrylic compound, generating the oxamniquine methacrylate copolymer (3). Submitted to a preliminary in vivo biological evaluation, a similar oxamniquine profile was observed to the monomeric forms although an inadequate drug release may be responsible for the methacrylic copolymer failure.

Starting from acrylic and methacrylic units, monomeric (derivatives 1 and 2) and polymeric prodrugs (derivative 3) of oxamniquine were designed with the purpose to prolong action. The compounds were tested in vivo and molecular modeling was applied to explain divergent results in oxamniquine’s reactivity.Figure optionsDownload as PowerPoint slide