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

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.

New 2-Acetyl-3-aminophenyl-1,4-naphthoquinones: Synthesis andIn VitroAntiproliferative Activities on Breast and Prostate Human Cancer Cells

“…It has to be mentioned that no attempts were made in order to decrease the reaction time formation of the arylation products. Based on our recent results [ 41 ] and that reported by Liu and Ji [ 42 ], on the arylamination of quinones, we will attempt, in future researches, the use of ultrasound to accelerate the Ce(III)-promoted arylation reaction of acylnaphthoquinones with arenes in order to expand the 2-acetyl-3-aminoaryl-1,4-naphthoquinone series for further biological studies.…”

Short and Improved Synthesis of Cytotoxic Homodimers with an Isoquinoline Structure

“…Despite the homodimer 5 having two quinone moieties, it presents, similarly to the monomer derivative, two redox processes. This is due to the symmetry of the molecule and it has been shown in a precedent work that the bivalent compounds presents a two-electron-transfer in each process [44]. https://doi.org/10.37358/RC.20.5.8113 Table 2 shows for homodimer 5 a shift of the E I 1/2 to more positives values compared with 7, this is an expected result since ester group is more electron-withdrawing than acetyl group.…”

Effect of substituents and chain length in amino-1,4-naphthoquinones on glutathione-S-transferase inhibition: molecular docking and electrochemical perspectives: a structure–activity study

“…The synthesis of the new amino-1,4-naphthoquinones and amino-bis-1,4-naphthoquinones are based on the identical twin-drug approach, in which the objective is to produce more potent drugs and/or more selectivity compared to the single entity. 39–41,44 The one-pot reactions are based on oxidative amination of the precursor 1,4-naphthoquinones 1–3 with diamines 4–7 to give the respective homodimers, monoamination products, and their respective pharmacophores (Fig. 1).…”

“…Following previous protocols by Ibacache et al , 39–41 the new amino-1,4-naphthoquinone derivatives 8–23 were synthesized through one-pot reactions, in which the molar ratio of quinones 1–3 and diamines 4–7 was changed to obtain either the homodimer or the monoamination product. To form homodimers 14–17 , a 4 : 1 molar ratio of quinones 1 and 2 with diamines 4 and 5 was used, whereas for monoamination products 8–13 and 21–23 and pharmacophores 18–20 , the molar ratio was 2 : 1; the reactions were carried out at room temperature in the presence of catalytic amounts of CeCl 3 ·7H 2 O, giving yields between 25 and 92% (Scheme 1).…”

“…Herein, we report a number of synthetic amino-1,4-naphthoquinones and homodimer analogs applying the twin-drug approach whose purpose is the production of a more potent and/or selective drug compared to its unique identity. 39–41 To establish an activity–structure relationship in GST inhibition, three precursors of naphthoquinones were used: 2,3-dichloro-1,4-naphthoquinone ( 1 ), 1,4-naphthoquinone ( 2 ), and 2-hydroxi-1,4-naphthoquinone ( 3 ). The choice of these precursor quinones is based on the structure of diospirine, a bis-naphthoquinone, and its derivatives, in which the presence of a chlorine group has been shown to increase the antitumor activity for the amino-1,4-naphthoquinone series.…”