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

  • Eur J Med Chem. 2014 Oct 30:86:291-309. doi: 10.1016/j.ejmech.2014.08.055.
María C Blanco  1 ,  Patricia Escobar  2 ,  Sandra M Leal  2 ,  Alí Bahsas  3 ,  Justo Cobo  4 ,  Manuel Nogueras  4 ,  Alirio Palma  5
Affiliations
  • 1. Laboratorio de Síntesis Orgánica, Escuela de Química, Universidad Industrial de Santander, A.A. 678, Bucaramanga, Santander, Colombia.
  • 2. Centro de Investigación de Enfermedades Tropicales, Departamento de Ciencias Básicas, Escuela de Medicina, Universidad Industrial de Santander, A.A. 678, Bucaramanga, Santander, Colombia.
  • 3. Laboratorio de RMN, Grupo de Productos Naturales, Departamento de Química, Universidad de los Andes, Mérida 5101, Venezuela.
  • 4. Inorganic and Organic Department, University of Jaén, Campus Las Lagunillas s/n, 23071 Jaén, Spain.
  • 5. Laboratorio de Síntesis Orgánica, Escuela de Química, Universidad Industrial de Santander, A.A. 678, Bucaramanga, Santander, Colombia. Electronic address: [email protected].
PMID: 25173828 DOI: 10.1016/j.ejmech.2014.08.055
Abstract

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.

Keywords
(2SR,4RS)-2-heteroaryltetrahydro-1,4-epoxy-1-benzazepines; Antiparasitic activity; Cytotoxicity; Leishmania (Leishmania) infantum; Trypanosoma cruzi; cis-2-Heteroaryltetrahydro-1H-1-benzazepin-4-ols.