Ruthenium–Arene Complexes of Curcumin: X-Ray and Density Functional Theory Structure, Synthesis, and Spectroscopic Characterization, in Vitro Antitumor Activity, and DNA Docking Studies of (p-Cymene)Ru(curcuminato)chloro

Abstract

The in vitro antiproliferative activity of the title compound on five tumor cell lines shows preference for the colon-rectal tumor HCT116, IC(50) = 13.98 μM, followed by breast MCF7 (19.58 μM) and ovarian A2780 (23.38 μM) cell lines; human glioblastoma U-87 and lung carcinoma A549 are less sensitive. A commercial curcumin reagent, also containing demethoxy and bis-demethoxy curcumin, was used to synthesize the title compound, and so (p-cymene)Ru(demethoxy-curcuminato)chloro was also isolated and chemically characterized. The crystal structure of the title compound shows (1) the chlorine atom linking two neighboring complexes through H-bonds with two O(hydroxyl), forming an infinite two-step network; (2) significant twist in the curcuminato, 20° between the planes of the two phenyl rings. This was also seen in the docking of the Ru-complex onto a rich guanine B-DNA decamer, where a Ru-N7(guanine) interaction is detected. This Ru-N7(guanine) interaction is also seen with ESI-MS on a Ru-complex-guanosine derivative.

The in vitro antitumor activity of arene-ruthenium(II) curcuminoid complexes improves when decreasing curcumin polarity

“…It seems that limited efforts have been made in conjugating the metal center with such ligands and so we are investigating the chemistry and potential antitumor activity of novel arene Ru II complexes with structural variants of curcumin [34], a molecule showing remarkable anti-inflammatory, anti-angiogenic, anti-oxidant, wound healing and anti-cancer properties [35]. The use of curcumin, defined as the Indian solid gold [36], as a coordinating ligand is of interest in bioinorganic chemistry since it is edible in large amounts (up to 10 g daily) and innocuous.…”

Development of ruthenium-based complexes as anticancer agents: toward a rational design of alternative receptor targets

“…The most studied organometallic compounds are based on the Ru-arene scaffold-bearing monodentate and bidentate ligands, such as halides or dicarboxylates as leaving groups and 1,2-ethylenediamine (en), PTA, pyrone, and paullone derivatives, as well as other activitydetermining moieties , Süss-Fink 2010, Barry and Sadler 2012, Caruso et al 2012, Gligorijević et al 2012, Mitra et al 2012. It has been shown analytically that most of the Ru-based anticancer agents mentioned are capable of binding strongly to biological nucleophiles, especially those bearing halides that proceed via their replacement with soft donor atoms, such as the imidazole of histidine, the thiol of cysteine, or the thioether of methionine, in the case of proteins or with N7 of purine bases, predominantly guanine, in the case of DNA (Caruso et al 2012).…”

Report of Interaction Between Calf Thymus DNA and Pyrimidine-Annulated Spiro-Dihydrofuran

“…Molecular docking technique is an attractive scaffold to understand the Drug-DNA interactions for the rational drug design and discovery, as well as in the mechanistic study by placing a small molecule into the binding site of the target specific region of the DNA mainly in a non-covalent fashion [41,42].…”