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1,2,5-Oxadiazole N -Oxide Derivatives and Related Compounds as Potential Antitrypanosomal Drugs: Structure−Activity Relationships

1999; American Chemical Society; Volume: 42; Issue: 11 Linguagem: Inglês

10.1021/jm9805790

1520-4804

Hugo Cerecetto, Rossanna Di Maio, Mercedes González, Mariela Risso, Patricia Saenz‐Méndez, Gustavo Seoane, Ana Denicola, Gonzalo Peluffo, Celia Quijano, Claudio Olea‐Azar,

Free Radicals and Antioxidants

The syntheses of a new series of derivatives of 1,2,5-oxadiazole N-oxide, benzo[1,2-c]1,2,5-oxadiazole N-oxide, and quinoxaline di-N-oxide are described. In vitro antitrypanosomal activity of these compounds was tested against epimastigote forms of Trypanosoma cruzi. For the most effective drugs, derivatives IIIe and IIIf, the 50% inhibitory dose (ID50) was determined as well as their cytotoxicity against mammalian fibroblasts. Electrochemical studies and ESR spectroscopy show that the highest activities observed are associated with the facile monoelectronation of the N-oxide moiety. Lipophilic−hydrophilic balance of the compounds could also play an important role in their effectiveness as antichagasic drugs.