title: Synthesis and in vitro evaluation of potential antichagasic hydroxymethylnitrofurazone (NFOH-121): a new nitrofurazone prodrug.
abstract: The synthesis of mutual prodrugs of nitrofurazone with primaquine, using specific and nonspecific spacer groups, has been previously attempted seeking selective antichagasic agents. The intermediate reaction product, hydroxymethylnitrofurazone (NFOH-121), was isolated and tested in LLC-MK(2) culture cells infected with trypomastigotes forms of Trypanosoma cruzi showing higher trypanocidal activity than nitrofurazone and benznidazol in all stages. The mutagenicity tests showed that the prodrug was less toxic than the parent drug. Degradation assays were carried out in pH 1.2 and 7.4.
authors.affiliation: Lapdesf- Laboratório de Pesquisa e Desenvolvimento de Fármacos, Departamento de Fármacos e Medicamentos, Faculdade de Ciências Farmacêuticas, UNESP, Araraquara, Caixa Postal 502, CEP 14.801-902, SP, Brazil.
authors.forename: Man-Chin
authors.initials: MC
authors.lastname: Chung
authors.forename: Rafael Victório Carvalho
authors.initials: RV
authors.lastname: Güido
authors.forename: Tatiane Favarato
authors.initials: TF
authors.lastname: Martinelli
authors.forename: Marinei Ferreira
authors.initials: MF
authors.lastname: Gonçalves
authors.forename: Michelle Carneiro
authors.initials: MC
authors.lastname: Polli
authors.forename: Katia Cirlene Alves
authors.initials: KC
authors.lastname: Botelho
authors.forename: Eliana Aparecida
authors.initials: EA
authors.lastname: Varanda
authors.forename: Walter
authors.initials: W
authors.lastname: Colli
authors.forename: M Terêsa M
authors.initials: MT
authors.lastname: Miranda
authors.forename: Elizabeth Igne
authors.initials: EI
authors.lastname: Ferreira
mesh_terms: D000818:Animals; D002460:Cell Line; D014355:Chagas Disease; D008253:Macaca mulatta; D009152:Mutagenicity Tests / Q000379:methods; D009583:Nitrofurazone / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology*; D011355:Prodrugs / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D013056:Spectrophotometry, Ultraviolet; D014344:Trypanocidal Agents / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology*; D014349:Trypanosoma cruzi / Q000187:drug effects / Q000502:physiology
chemical_list: D011355:Prodrugs; D014344:Trypanocidal Agents; C483719:hydroxymethylnitrofurazone; D009583:Nitrofurazone