jm9805790_si_001.pdf (173.64 kB)
1,2,5-Oxadiazole N-Oxide Derivatives and Related Compounds as Potential Antitrypanosomal Drugs: Structure−Activity Relationships
journal contribution
posted on 1999-05-06, 00:00 authored by Hugo Cerecetto, Rossanna Di Maio, Mercedes González, Mariela Risso, Patricia Saenz, Gustavo Seoane, Ana Denicola, Gonzalo Peluffo, Celia Quijano, Claudio Olea-AzarThe 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.