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

Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry
Juana Andrea IbacacheJaime A Valderrama

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.

References

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Jun 9, 2012·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Virginia DelgadoJaime A Valderrama
Jan 10, 2013·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Virginia DelgadoJaime A Valderrama
Jan 11, 2014·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Juana Andrea IbacacheJaime A Valderrama
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Citations

Jan 3, 2020·Organic & Biomolecular Chemistry·Ryan D KruschelFlorence O McCarthy
May 11, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Julio BenitesPedro Buc Calderon
Dec 6, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Juana Andrea IbacacheCésar A Zúñiga

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Methods Mentioned

BETA
column chromatography
infrared spectroscopy
NMR

Software Mentioned

GraphPad Prisma

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