Preparation of Novel Homodimers Derived from Cytotoxic Isoquinolinequinones. A Twin Drug Approach

Ibacache, Juana Andrea; Faundes, Judith; Montoya, Margarita; Mejías, Sophia; Valderrama, Jaime A.

doi:10.3390/molecules23020439

Open AccessArticle

Preparation of Novel Homodimers Derived from Cytotoxic Isoquinolinequinones. A Twin Drug Approach

by

Juana Andrea Ibacache

^1,*,

Judith Faundes

¹,

Margarita Montoya

¹,

Sophia Mejías

¹ and

Jaime A. Valderrama

^2,*

¹

Facultad de Química y Biología, Universidad de Santiago de Chile, Alameda 3363, Casilla 40, Santiago 9170022, Chile

²

Facultad de Ciencias de la Salud, Universidad Arturo Prat, Casilla 121, Iquique 1100000, Chile

^*

Authors to whom correspondence should be addressed.

Molecules 2018, 23(2), 439; https://doi.org/10.3390/molecules23020439

Submission received: 8 January 2018 / Revised: 13 February 2018 / Accepted: 14 February 2018 / Published: 16 February 2018

(This article belongs to the Section Organic Chemistry)

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Abstract

The synthesis of five novel homodimers is reported based on the anilinoisoquinolinequinone scaffold. In these twin-drug derivatives, two units of the anilinoquinone pharmacophores are linked through a methylene spacer. The formation of dimers was achieved by reaction of isoquinolinequinones with 4, 4’-diaminodiphenylmethane via a sequence of two oxidative amination reactions. A preliminary in vitro screening of the homodimers reveals moderate to high cytotoxic activities against MDA-MB-21 breast adenocarcinoma and B16-F10 murine metastatic melanoma cell lines. The asymmetrical homodimer 15 stands out due to its cytotoxic potencies at submicromolar concentrations and high selectivity index (mean IC₅₀ = 0.37 μM; SI = 6.97) compared to those of etoposide (mean IC₅₀ = 3.67; SI = 0.32) and taxol (mean IC₅₀ = 0.35; SI = 0.91) employed as reference anticancer drugs.

Keywords: anilinoisoquinolinequinones; twin drugs; homodimers; amination reaction; cytotoxic activity

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MDPI and ACS Style

Ibacache, J.A.; Faundes, J.; Montoya, M.; Mejías, S.; Valderrama, J.A. Preparation of Novel Homodimers Derived from Cytotoxic Isoquinolinequinones. A Twin Drug Approach. Molecules 2018, 23, 439. https://doi.org/10.3390/molecules23020439

AMA Style

Ibacache JA, Faundes J, Montoya M, Mejías S, Valderrama JA. Preparation of Novel Homodimers Derived from Cytotoxic Isoquinolinequinones. A Twin Drug Approach. Molecules. 2018; 23(2):439. https://doi.org/10.3390/molecules23020439

Chicago/Turabian Style

Ibacache, Juana Andrea, Judith Faundes, Margarita Montoya, Sophia Mejías, and Jaime A. Valderrama. 2018. "Preparation of Novel Homodimers Derived from Cytotoxic Isoquinolinequinones. A Twin Drug Approach" Molecules 23, no. 2: 439. https://doi.org/10.3390/molecules23020439

APA Style

Ibacache, J. A., Faundes, J., Montoya, M., Mejías, S., & Valderrama, J. A. (2018). Preparation of Novel Homodimers Derived from Cytotoxic Isoquinolinequinones. A Twin Drug Approach. Molecules, 23(2), 439. https://doi.org/10.3390/molecules23020439

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Preparation of Novel Homodimers Derived from Cytotoxic Isoquinolinequinones. A Twin Drug Approach

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