Synthesis of novel polysubstituted (2SR,4RS)-2-heteroaryltetrahydro-1,4-epoxy-1-benzazepines and cis-2-heteroaryl-4-hydroxytetrahydro-1H-1-benzazepines as antiparasitic agents

•Synthesized compounds were tested for their in vitro antiparasitic activity.•Many of the tested compounds inhibited significantly the growth of epimastigotes.•Many of the tested compounds inhibited significantly the growth of promastigotes.•Two compounds demonstrated good activity against Trypanosoma cruzi amastigotes.•Most of the evaluated compounds were nontoxic to Vero and HTP-1 cells.

New series of polysubstituted (2SR,4RS)-2-heteroaryltetrahydro-1,4-epoxy-1-benzazepines and cis-2-heteroaryl-4-hydroxytetrahydro-1H-1-benzazepines were designed and synthesized in moderate to high yields using a three-step procedure from ortho-allylanilines. Their antiparasitic activity was evaluated against the extracellular and intracellular forms of Trypanosoma cruzi and Leishmania (Leishmania) infantum parasites. Their cytotoxicity was also determined on Vero and THP-1 mammalian cells. Many of the tested compounds inhibited significantly the growth of extracellular forms of T. cruzi and L. (L.) infantum without showing cytotoxicity on Vero and HTP-1 cells. Only compounds 10h and 14f demonstrated good activity against amastigotes of T. cruzi, but none was able to inhibit the growth of L. (L.) infantum amastigotes.

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