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.
Filho
Roberto Parise
RP
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
de Souza Menezes
Carla Maria
CM
Pinto
Pedro Luiz Silva
PL
Paula
Gilberto Alvarenga
GA
Brandt
Carlos Alberto
CA
da Silveira
Maria Amélia Barata
MA
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
D008689:Methacrylates; D011355:Prodrugs; D012556:Schistosomicides; D010073:Oxamniquine; D020106:Acrylamide