Luminescent alkynyl-gold(i) coumarin derivatives and their biological activity

Abstract

The synthesis and characterization of three propynyloxycoumarins are reported in this work together with the formation of three different series of gold(i) organometallic complexes. Neutral complexes are constituted by water soluble phosphines (PTA and DAPTA) which confer water solubility to them. The X-ray crystal structure of 7-(prop-2-in-1-yloxy)-1-benzopyran-2-one and its corresponding dialkynyl complex is also shown and the formation of rectangular dimers for the gold derivative in the solid state can be observed. A detailed analysis of the absorption and emission spectra of both ligands and complexes allows us to attribute the luminescent behaviour to the coumarin organic ligand. Moreover, the presence of the gold(i) metal atom seems to be responsible for an increase of coumarin phosphorescence emission. The biological activity of the complexes showed that the anionic complexes triggered strong cytotoxic effects in two different cell lines whereas the neutral gold alkynyl complexes led to lower effects against tumor cell growth. Thioredoxin reductase (TrxR) inhibition was very strong in the case of the neutral complexes (IC50 values below 0.1 μM) but moderate for the anionic complexes (IC50 values above 0.8 μM).

The Important Role of the Nuclearity, Rigidity, and Solubility of Phosphane Ligands in the Biological Activity of Gold(I) Complexes

“…All the synthesized complexes gave satisfactory elemental analysis and were characterized by 1 H and 31 P NMR and IR spectroscopy as well as by ESI‐MS(+) spectrometry. The 31 P{ 1 H} NMR spectra display in all cases a single resonance, which is around 50 ppm downfield from the resonance of the corresponding free phosphine . Only one peak was recorded for the diphosphine derivatives 7 – 10 , in agreement with the formation of symmetrical dinuclear complexes (see the Supporting Information).…”

In vitro and in vivo evaluation of organometallic gold(i) derivatives as anticancer agents

“…Several properties of these compounds offer plenty of opportunities in the design of new coordination of carbenes and alkyne ligands. As stated above, there is a huge number of gold(I) carbenes with antitumor activity described in the literature, however alkyne gold(I) complexes with potential anticancer behaviour are much less represented [50][51][52][53][54][55] .…”

Recent advances in 4-hydroxycoumarin chemistry. Part 1: Synthesis and reactions

“…Bromination of 4-hydroxycoumarin 1 with bromine in acetic acid (Anand et al, 2011;Arcau et al, 2014) or chloroform (Kotharkar and Shinde, 2006) Scheme 97.…”

“…O-methylation of 4-hydroxycoumarin 1 is also readily performed under microwave irradiation in the presence of dry dimethyl sulphate to give 4-methoxycoumarin 141 (Cao et al, 2014;Garro Hugo et al, 2014;Mitra et al, 2000) The base catalyzed alkylation of 4-hydroxycoumarin 1 with ethyl bromoacetate or chloroacetic acid 143 afforded ethyl (coumarin-4-oxy)acetate 144 (Abd Elhafez et al, 2003;Chimichi et al, 2002;Dahiya et al, 2010) Scheme 81. A number of studies have investigated the O-alkylation of 4-hydroxycoumarin 1 with allyl halides 155 in acetone (Avetisyan and Alvandzhyan, 2006;Majumdar et al, 2004;Patent, 2005) or DMF (Vasudevan et al, 2010) Coumarin-4-yl-prop-2-ynyl ether 158 was obtained via refluxing of 4-hydroxycoumarin 1 with propargyl bromide 157 and potassium carbonate in dry acetone or in the presence of tetrabutylammonium bromide (Anand et al, 2011;Arcau et al, 2014; Scheme 84.…”