Copper Curcuminoids Containing Anthracene Groups: Fluorescent Molecules with Cytotoxic Activity

Abstract

The coordination chemistry of the new curcuminoid ligand, 1,7-(di-9-anthracene-1,6-heptadiene-3,5-dione), abbreviated 9Accm has been studied, resulting in two new copper-9Accm compounds. Compound 1, [Cu(phen)Cl(9Accm)], was synthesized by reacting 9Accm with [Cu(phen)Cl(2)] in a 1:1 ratio (M:L) and compound 2, [Cu(9Accm)(2)], was prepared from Cu(OAc)(2) and 9Accm (1:2). UV-vis, electron paramagnetic resonance (EPR), and superconducting quantum interference device (SQUID) measurements were some of the techniques employed to portray these species; studies on single crystals of free 9Accm, [Cu(phen)Cl(9Accm)] and [Cu(9Accm)(2)(py)] provided detailed structural information about compounds 1 and 2·py, being the first two copper-curcuminoids crystallographically described. In addition the antitumor activity of the new compounds was studied and compared with free 9Accm for a number of human tumor cells. To provide more insight on the mode of action of these compounds under biological conditions, additional experiments were accomplished, including studies on the nature of their interactions with calf thymus DNA by UV-vis titration and Circular Dichroism. These experiments together with DNA-binding studies indicate electrostatic interactions between some of these species and the double helix, pointing out the weak nature of the interaction of the compounds with CT-DNA. The intrinsic fluorescence of the free ligand and both copper compounds provided valuable information over the cellular process and therefore, fluorescence microscopy studies were performed using a human osteosarcoma cell line. Studies in vitro using this technique suggest that the action of these molecules seems to occur outside the nuclei.

Comparative Magnetic Studies in the Solid State and Solution of Two Isostructural 1D Coordination Polymers Containing CoII/NiII-Curcuminoid Moieties

“…As has been observed in previous M-CCMoid systems (M = metal centre) containing monocoordinate pyridine derivatives [22], the 9Accm ligands are disposed in a trans conformation providing an ideal D 4h geometry. In both systems, 1 and 2, such organic ligands show two alternating C-C values related to the double/single bonds, typical of CCMoid chains and similar to others [15][16][17][18][19][20]22]. The conjugated skeletons of the two species present exclusively zig-zag conformations, when in the past similar mononuclear units have displayed both zig-zag and boat shapes [22].…”

“…Solvents were distilled for the UV-vis, fluorescence and nano-structuration studies. The 9Accm was synthesized according to the procedure described elsewhere [15]. Compound 2 was achieved by modifying the methodology used elsewhere [20].…”

“…No additional π-π stacking or hydrogen bondings were observed in the two structures. [15][16][17][18][19][20]22]. The conjugated skeletons of the two species present exclusively zig-zag conformations, when in the past similar mononuclear units have displayed both zig-zag and boat shapes [22].…”

“…Regarding the latest idea, here we report our first studies with two isostructural Co II /Ni II chains, systems 1 and 2, containing a curcuminoid (CCMoid) ligand, described before, called 9Accm [15][16][17][18][19][20]. Systems 1 and 2 are coordination polymers formed by the periodic repetition of "[M(9Accm) 2 ]" units linked through 4,4'-bpy molecules, well known as structural connectors [21].…”

Perspectives on New Synthetic Curcumin Analogs and their Potential Anticancer Properties

“…Alcalde et al [105] have investigated a new curcuminoid ligand, viz. 9Accm (Compound 144) and its corresponding copper-complex, [Cu(phen)Cl(9Accm)] for their interactions with calf thymus DNA which indicate a weak electrostatic interaction with the double helix.…”