Synthesis and in vitro evaluation of potential antichagasic hydroxymethylnitrofurazone (NFOH-121): a new nitrofurazone prodrug.
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.
Chung
Man-Chin
MC
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.
Güido
Rafael Victório Carvalho
RV
Martinelli
Tatiane Favarato
TF
Gonçalves
Marinei Ferreira
MF
Polli
Michelle Carneiro
MC
Botelho
Katia Cirlene Alves
KC
Varanda
Eliana Aparecida
EA
Colli
Walter
W
Miranda
M Terêsa M
MT
Ferreira
Elizabeth Igne
EI
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
D011355:Prodrugs; D014344:Trypanocidal Agents; C483719:hydroxymethylnitrofurazone; D009583:Nitrofurazone