2. Academic Validation
  3. 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

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

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: apalma@uis.edu.co.
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.

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