title: Design, synthesis, and in vivo evaluation of oxamniquine methacrylate and acrylamide prodrugs.
abstract: 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.
authors.affiliation: Department of Pharmacy, Faculty of Pharmaceutical Sciences, University of São Paulo, Av. Prof. Lineu Prestes, 580, ZIP 05508-900 São Paulo, Brazil. rparisef@usp.br
authors.forename: Roberto Parise
authors.initials: RP
authors.lastname: Filho
authors.forename: Carla Maria
authors.initials: CM
authors.lastname: de Souza Menezes
authors.forename: Pedro Luiz Silva
authors.initials: PL
authors.lastname: Pinto
authors.forename: Gilberto Alvarenga
authors.initials: GA
authors.lastname: Paula
authors.forename: Carlos Alberto
authors.initials: CA
authors.lastname: Brandt
authors.forename: Maria Amélia Barata
authors.initials: MA
authors.lastname: da Silveira
mesh_terms: D020106:Acrylamide / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use; D000818:Animals; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D008297:Male; D008642:Mesenteric Veins / Q000187:drug effects; D008689:Methacrylates / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use; D051379:Mice; D008958:Models, Molecular; D010073:Oxamniquine / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use; D011355:Prodrugs / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use; D012550:Schistosoma mansoni / Q000187:drug effects; D012555:Schistosomiasis mansoni / Q000188:drug therapy; D012556:Schistosomicides / Q000138:chemical synthesis / Q000627:therapeutic use*; D013329:Structure-Activity Relationship
chemical_list: D008689:Methacrylates; D011355:Prodrugs; D012556:Schistosomicides; D010073:Oxamniquine; D020106:Acrylamide