Synthesis and in vitro antitrypanosomal activity of novel Nifurtimox analogues.
Eight novel analogues of Nifurtimox, 4-[(5-nitrofurfurylidene)amino]-3-methylthiomorpholine-1,1-dioxide, containing alpha-beta unsaturated amides, were synthesized and evaluated for their in vitro activity against Trypanosoma cruzi epimastigotes. Four derivatives bearing a nitro group at the 5-position of the furan ring were the most active in inhibiting culture growth and provoking cell death, showing trypanocidal activity more than threefold the potency of Nifurtimox, our positive control. Two derivatives lacking a nitro group were less potent than the positive control. Active nitro derivatives very efficiently caused epimastigote death, which suggests a nitro reduction mechanism of action.
Pozas
Rocío
R
Departamento de Química Orgánica, Facultad de Química, Universidad Nacional Autónoma de México, C.U. México DF 04510, Mexico.
Carballo
Javier
J
Castro
Clementina
C
Rubio
Julieta
J
D000818:Animals; D015394:Molecular Structure; D009547:Nifurtimox / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000494:pharmacology; D021261:Parasitic Sensitivity Tests; D013329:Structure-Activity Relationship; D014344:Trypanocidal Agents / Q000138:chemical synthesis / Q000494:pharmacology; D014349:Trypanosoma cruzi / Q000187:drug effects*
D014344:Trypanocidal Agents; D009547:Nifurtimox