Short and Improved Synthesis of Cytotoxic Homodimers with an Isoquinoline Structure

Abstract

The syntheses of cytotoxic homodimers 5, 7-10 are described. Compounds 5, 7-10 were cleanly and efficiently obtained by microwave activation. A thorough study concerning oxidative reaction of diamines and isoquinolinequinones, under ultrasound (US) and microwave (MW) irradiation is presented. Under MW irradiation the yields are higher, the amount of precursor quinone used decreases substantially, the reaction time decreases considerably (from hours to minutes) in respect to previously reported methodology.

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.…”

The use of ultrasound in the South Cone region. Advances in organic and inorganic synthesis and in analytical methods

“…Meza et al . at Universidad de Santiago de Chile, Chile [40] , described the synthesis of a set of cytotoxic homodimers with an isoquinoline moiety ( Scheme 29 ). The authors presented a thorough study concerning the oxidative synthesis of compounds ( 107 ), with isoquinolinequinones ( 105 ) and diamine 4,4́-diaminodiphenylmethane ( 106 ), under conventional thermal heating, ultrasound and microwave irradiation, in the presence or absence of CeCl 3 ·7H 2 O catalyst.…”