Green Synthesis and Electrochemical Properties of Mono- and Dimers Derived from Phenylaminoisoquinolinequinones.

Juana Andrea Ibacache,Francisco J Recio,Judith Faúndes,Alex Danimann,Jaime A Valderrama,César A Zúñiga

doi:10.3390/molecules24234378

Abstract

In the search for new quinoid compounds endowed with potential anticancer activity, the synthesis of novel heterodimers containing the cytotoxic 7-phenylaminoisoquinolinequinone and 2-phenylaminonaphthoquinone pharmacophores, connected through methylene and ethylene spacers, is reported. The heterodimers were prepared from their respective isoquinoline and naphthoquinones and 4,4′-diaminodiphenyl alkenes. The access to the target heterodimers and their corresponding monomers was performed both through oxidative amination reactions assisted by ultrasound and CeCl3·7H2O catalysis “in water”. This eco-friendly procedure was successfully extended to the one-pot synthesis of homodimers derived from the 7-phenylaminoisoquinolinequinone pharmacophore. The electrochemical properties of the monomers and dimers were determined by cyclic and square wave voltammetry. The number of electrons transferred during the oxidation process, associated to the redox potential EI1/2, was determined by controlled potential coulometry.

Highlights

The strategy to construct the the heterodimers, where the phenylamino groups of theofselected quinoid quinoid pharmacophores are connected through methylene spacers, is based on oxidative pharmacophores are connected through methylene spacers, is based on oxidative monoamination
We have synthesized a series of novel heterodimers containing the cytotoxic
7-phenylaminoisoquinolinequinone and 2-phenylaminonaphthoquinone pharmacophores connected through methylene and ethylene spacers

Summary

Introduction

Quinones are ubiquitous in nature and comprise one of the largest classes of anticancer agents [1,2,3].Among the broad variety of drugs used clinically in the therapy of solid cancers, mitomycin, mitoxantrone, and saintopin contain the common quinone nucleus into their active pharmacophores.The most remarkable characteristics of these quinoid drugs are their abilities to act as DNA intercalators, reductive alkylators of biomolecules, and/or generators of reactive oxygen species (ROS) such as hydroxyl radical, hydrogen peroxide, superoxide anion, and singlet oxygen [4], which can damage tumor cells [5,6,7,8,9,10,11,12] via oxidative stress [5,13,14]. Among the broad variety of drugs used clinically in the therapy of solid cancers, mitomycin, mitoxantrone, and saintopin contain the common quinone nucleus into their active pharmacophores. A common aminoquinoid unit appeared as a key structural scaffold in diverse natural occurring cytotoxic compounds, such as smenospongine [16,17], streptonigrin [18,19,20,21,22,23], mansouramicyn C [24,25]. A number of synthetic aminoisoquinolinequinones and polycyclic analogs have been the subject of study for many years due to their in vitro cytotoxic activities on several cancer cell lines [33,34,35,36,37,38,39]

Methods

Results

Conclusion