Copper curcuminoids containing anthracene groups: fluorescent molecules with cytotoxic activity.
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.
Aliaga-Alcalde
Núria
N
Institut Català de Recerca i Estudis Avançats and Universitat de Barcelona, Facultat de Química, Martí i Franquès, 1-11, 08028 Barcelona, Spain. nuria.aliaga@icrea.cat
Marqués-Gallego
Patricia
P
Kraaijkamp
Mirte
M
Herranz-Lancho
Coral
C
den Dulk
Hans
H
Görner
Helmut
H
Roubeau
Olivier
O
Teat
Simon J
SJ
Weyhermüller
Thomas
T
Reedijk
Jan
J
D000873:Anthracenes / Q000737:chemistry*; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D045744:Cell Line, Tumor; D003300:Copper / Q000737:chemistry*; D018360:Crystallography, X-Ray; D003474:Curcumin / Q000031:analogs & derivatives* / Q000737:chemistry*; D004247:DNA / Q000378:metabolism; D005456:Fluorescent Dyes / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D008958:Models, Molecular; D008968:Molecular Conformation; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D013057:Spectrum Analysis
C555446:1,7-(di-9-anthracene-1,6-heptadiene-3,5-dione); D000873:Anthracenes; D000970:Antineoplastic Agents; D005456:Fluorescent Dyes; D009942:Organometallic Compounds; D003300:Copper; D004247:DNA; C034020:anthracene; D003474:Curcumin