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

Ricardo A. Tapia; Cristian O. Salas; Karina Vázquez; Christian Espinosa-Bustos; Jorge Soto-Delgado; Javier Varela; Estefanía Birriel; Hugo Cerecetto; Mercedes González; Margot Paulino

doi:10.1016/j.bmcl.2014.06.044

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

Ricardo A. Tapia, Cristian O. Salas, Karina Vázquez, Christian Espinosa-Bustos, Jorge Soto-Delgado, Javier Varela, Estefanía Birriel, Hugo Cerecetto, Mercedes González, Margot Paulino

Exact Sciences School

Research output: Contribution to journal › Article › peer-review

16 Citations (Scopus)

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.

Original language	English
Pages (from-to)	3919-3922
Number of pages	4
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	24
Issue number	16
DOIs	https://doi.org/10.1016/j.bmcl.2014.06.044
Publication status	Published - 15 Aug 2014

Keywords

Anti-T. cruzi
Cytotoxicity
Indolequinones
Pharmacophore model

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Molecular Biology
Pharmaceutical Science
Drug Discovery
Clinical Biochemistry
Organic Chemistry

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10.1016/j.bmcl.2014.06.044

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Tapia, R. A., Salas, C. O., Vázquez, K., Espinosa-Bustos, C., Soto-Delgado, J., Varela, J., Birriel, E., Cerecetto, H., González, M., & Paulino, M. (2014). Synthesis and biological characterization of new aryloxyindole-4,9-diones as potent trypanosomicidal agents. Bioorganic and Medicinal Chemistry Letters, 24(16), 3919-3922. https://doi.org/10.1016/j.bmcl.2014.06.044

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

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",

author = "Tapia, {Ricardo A.} and Salas, {Cristian O.} and Karina V{\'a}zquez and Christian Espinosa-Bustos and Jorge Soto-Delgado and Javier Varela and Estefan{\'i}a Birriel and Hugo Cerecetto and Mercedes Gonz{\'a}lez and Margot Paulino",

year = "2014",

month = aug,

day = "15",

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journal = "Bioorganic and Medicinal Chemistry Letters",

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Tapia, RA, Salas, CO, Vázquez, K, Espinosa-Bustos, C, Soto-Delgado, J, Varela, J, Birriel, E, Cerecetto, H, González, M & Paulino, M 2014, 'Synthesis and biological characterization of new aryloxyindole-4,9-diones as potent trypanosomicidal agents', Bioorganic and Medicinal Chemistry Letters, vol. 24, no. 16, pp. 3919-3922. https://doi.org/10.1016/j.bmcl.2014.06.044

TY - JOUR

T1 - Synthesis and biological characterization of new aryloxyindole-4,9-diones as potent trypanosomicidal agents

AU - Tapia, Ricardo A.

AU - Salas, Cristian O.

AU - Vázquez, Karina

AU - Espinosa-Bustos, Christian

AU - Soto-Delgado, Jorge

AU - Varela, Javier

AU - Birriel, Estefanía

AU - Cerecetto, Hugo

AU - González, Mercedes

AU - Paulino, Margot

PY - 2014/8/15

Y1 - 2014/8/15

N2 - 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.

AB - 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.

KW - Anti-T. cruzi

KW - Cytotoxicity

KW - Indolequinones

KW - Pharmacophore model

UR - http://www.scopus.com/inward/record.url?scp=84906101091&partnerID=8YFLogxK

U2 - 10.1016/j.bmcl.2014.06.044

DO - 10.1016/j.bmcl.2014.06.044

M3 - Article

C2 - 25008454

AN - SCOPUS:84906101091

VL - 24

SP - 3919

EP - 3922

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

SN - 0960-894X

IS - 16

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

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