2. Academic Validation
  3. 2-Phenylaminonaphthoquinones and related compounds: synthesis, trypanocidal and cytotoxic activities

2-Phenylaminonaphthoquinones and related compounds: synthesis, trypanocidal and cytotoxic activities

  • Bioorg Med Chem. 2014 Sep 1;22(17):4609-20. doi: 10.1016/j.bmc.2014.07.030.
Ivan Sieveking 1,  Pablo Thomas 1,  Juan C Estévez 2,  Natalia Quiñones 3,  Mauricio A Cuéllar 3,  Juan Villena 4,  Christian Espinosa-Bustos 1,  Angélica Fierro 1,  Ricardo A Tapia 1,  Juan D Maya 5,  Rodrigo López-Muñoz 5,  Bruce K Cassels 6,  Ramon J Estévez 7,  Cristian O Salas 8
Affiliations

Affiliations

  • 1 Departamento de Química Orgánica, Facultad de Química, Pontificia Universidad Católica de Chile, 702843 Santiago de Chile, Chile.
  • 2 Centro Singular de Investigación en Química Biológica y Materiales Moleculares and Departamento de Química Orgánica (Facultad de Química), Universidad de Santiago de Compostela, 15782 Santiago de Compostela, Spain.
  • 3 Facultad de Farmacia, Universidad de Valparaíso, Av. Gran Bretaña N 1093, Valparaíso, Chile.
  • 4 Centro de Investigaciones Biomédicas, Escuela de Medicina, Universidad de Valparaíso, Av. Hontaneda N° 2664, Valparaíso, Chile.
  • 5 Instituto de Ciencias Biomédicas, Programa de Farmacología Molecular y Clínica, Universidad de Chile, PO Box 70000, Santiago, Chile.
  • 6 Departamento de Química, Facultad de Ciencias, Universidad de Chile, PO Box 653, Santiago, Chile.
  • 7 Centro Singular de Investigación en Química Biológica y Materiales Moleculares and Departamento de Química Orgánica (Facultad de Química), Universidad de Santiago de Compostela, 15782 Santiago de Compostela, Spain. Electronic address: ramon.estevez@usc.es.
  • 8 Departamento de Química Orgánica, Facultad de Química, Pontificia Universidad Católica de Chile, 702843 Santiago de Chile, Chile. Electronic address: cosalas@uc.cl.
PMID: 25127463 DOI: 10.1016/j.bmc.2014.07.030
Abstract

A series of new 2-aminonaphthoquinones and related compounds were synthesized and evaluated in vitro as trypanocidal and cytotoxic agents. Some tested compounds inhibited epimastigote growth and trypomastigote viability. Several compounds showed similar or higher activity and selectivity as compared with current trypanocidal drug, nifurtimox. Compound 4l exhibit higher selectivity than nifurtimox against Trypanosoma cruzi in comparison with Vero cells. Some of the synthesized Quinones were tested against Cancer cells and normal fibroblasts, showing that certain chemical modifications on the naphthoquinone moiety induce and excellent increase the selectivity index of the cytotoxicity (4g and 10). The results presented here show that the anti-T. cruzi activity of 2-aminonaphthoquinones derivatives can be improved by the replacement of the benzene ring by a pyridine moiety. Interestingly, the presence of a chlorine atom at C-3 and a highly lipophilic alkyl group or aromatic ring are newly observed elements that should lead to the discovery of more selective cytotoxic and trypanocidal compounds.

Keywords

2-Phenylaminonaphthoquinones; Benzocarbazolequinones; Cytotoxicity; Electronic properties; T. cruzi.

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