Synthesis, structural elucidation and in vitro antiparasitic activity against Trypanosoma cruzi and Leishmania chagasi parasites of novel tetrahydro-1-benzazepine derivatives.
Forty six new 1,4-epoxy-2-exo-aryl- and cis-2-aryl-4-hydroxytetrahydro-1-benzazepine derivatives were synthesized and fully characterized. All compounds were tested in vitro against both Trypanosoma cruzi and Leishmania chagasi parasites and also for cytotoxicity using Vero and THP-1 mammalian cell lines. Many of the evaluated compounds showed remarkable activity against the epimastigote and intracellular amastigote forms of T. cruzi, with IC₅₀ values comparable with that of control drug nifurtimox, a nitrofuran derivative currently used in the treatment of Chagas' disease. Other derivatives were found to have good activity against L. chagasi promastigotes, with low toxicity against the mammalian cells, but neither of them was active on intracellular amastigotes of L. chagasi infecting THP-1 macrophages.
Gómez-Ayala
Sandra
S
Laboratorio de Síntesis Orgánica, Escuela de Química, Universidad Industrial de Santander, A. A. 678, Bucaramanga, Santander, Colombia.
Castrillón
Julián A
JA
Palma
Alirio
A
Leal
Sandra M
SM
Escobar
Patricia
P
Bahsas
Alí
A
D000818:Animals; D000981:Antiprotozoal Agents / Q000138:chemical synthesis* / Q000627:therapeutic use / Q000633:toxicity; D001552:Benzazepines / Q000737:chemistry* / Q000627:therapeutic use / Q000633:toxicity; D002460:Cell Line; D014355:Chagas Disease / Q000188:drug therapy; D006801:Humans; D007893:Leishmania donovani / Q000187:drug effects*; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation; D014349:Trypanosoma cruzi / Q000187:drug effects*
D000981:Antiprotozoal Agents; D001552:Benzazepines