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Bioorg Med Chem Lett. 2014 Aug 15;24(16):3919-22. doi: 10.1016/j.bmcl.2014.06.044. Epub 2014 Jun 24.

Synthesis and biological characterization of new aryloxyindole-4,9-diones as potent trypanosomicidal agents.

Author information

1
Departamento de Química Orgánica, Facultad de Química, Pontificia Universidad Católica de Chile, Santiago 6094411, Chile. Electronic address: rtapia@uc.cl.
2
Departamento de Química Orgánica, Facultad de Química, Pontificia Universidad Católica de Chile, Santiago 6094411, Chile.
3
Grupo de Química Medicinal, Instituto de Química Biológica, Facultad de Ciencias, Universidad de la República, Iguá 4225, Montevideo, Uruguay.
4
Grupo de Química Medicinal, Instituto de Química Biológica, Facultad de Ciencias, Universidad de la República, Iguá 4225, Montevideo, Uruguay; Área de Radiofarmacia, Centro de Investigaciones Nucleares, Facultad de Ciencias, Universidad de la República, Mataojo 2055, Montevideo, Uruguay.
5
Centro de Bioinformática Estructural-DETEMA, Facultad de Química, Universidad de la República, C.C. 1157, Montevideo, Uruguay.

Abstract

A new indole-4,9-dione and their phenoxy derivatives were synthesized and evaluated in vitro against the epimastigote form of Trypanosoma cruzi, Y strain. All of these novel compounds were found to be extremely potent and selective that the standard drug nifurtimox. Interestingly, phenoxyindole-4,9-dione 9d displayed excellent nanomolar inhibitory activity, IC50=20 nM, and high selectivity index, SI=625. In silico studies using MOE program were performed to generate a preliminary pharmacophore model.

KEYWORDS:

Anti-T. cruzi; Cytotoxicity; Indolequinones; Pharmacophore model

PMID:
25008454
DOI:
10.1016/j.bmcl.2014.06.044
[Indexed for MEDLINE]

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