Ruthenium(II)–Arene RAPTA Type Complexes Containing Curcumin and Bisdemethoxycurcumin Display Potent and Selective Anticancer Activity

Abstract

A series of novel ruthenium(II) arene RAPTA type derivatives (arene = cymene, hexamethylbenzene) containing curcumin-based ligands (curcH = curcumin, bdcurcH = bisdemethoxycurcumin) and PTA (1,3,5-triaza-7-phosphaadamantane) have been synthesized and fully characterized. The solid-state structures of [Ru(cym)(curc)(PTA)][SO3CF3], [Ru(hmb)(curc)(PTA)][SO3CF3], and [Ru(hmb)(bdcurc)(PTA)][SO3CF3] have been determined by single-crystal X-ray diffraction. The antitumor activity of the complexes has been evaluated in vitro against human ovarian carcinoma cells (A2780 and A2780cisR), as well as against nontumorous human embryonic kidney (HEK293) cells. The correlation of the cytotoxicity upon switching the curcumin-based ligands, i.e. curcumin vs bisdemethoxycurcumin, is not straightforward. In contrast, the PTA ligand greatly enhances the activity and selectivity of ruthenium compounds in comparison to previously reported compounds

The development of anticancer ruthenium(ii) complexes: from single molecule compounds to nanomaterials

“…16) that were more inert towards hydration, and some of these complexes displayed efficacy similar to RAPTA-C in vitro . 169 However, the RAPTA derivatives were highly cytotoxic in A2780 and A2780cisR cell lines (IC 50 0.14–1.15 and 0.27–1.18 μM, respectively) and all the complexes with curcuminoid ligands were more efficacious than cisplatin. 169 …”

Discovery of a dual-targeting organometallic ruthenium complex with high activity inducing early stage apoptosis of cancer cells

“…[8][9][10][11][12][13][14][15][16][17][18][19] Two Ru III complexes, NAMI-A and KP1019 are now under phase II clinical trials, 20,21 and the organometallic half-sandwich ruthenium(II) complexes in type of [(η 6 -arene)Ru(X)(Y)(Z)] have been extensively studied in recent years. [22][23][24][25][26] This kind of complexes adopt an octahedral geometry, of which three coordination sites are occupied by arene ligands, stabilizing the ruthenium centre in +2 oxidative status, and other three sites offer possibilities for coordination with a variety of ligands to tune their biological activities, such as hydrophobicity, cellular uptake, reactivity and selectivity towards biological targets. [6][7][8]27 For instance, the {(η 6 -arene)Ru} (arene = cyclopentadienyl, benzene, p-cymene, biphenyl, etc.)…”

Hydrogen Bonding and Anticancer Properties of Water‐Soluble Chiral p‐Cymene RuII Compounds with Amino‐Oxime Ligands

“…[1,2] From the plethora of transition metal-based compounds synthesized and studied as potential antitumor agents during the last decade, ruthenium derivatives have emerged as promising candidates. [2,3,4–8] Some Ru(III) compounds, NAMI-A (imidazolium trans-[tetrachloridobis(dimethylsulfoxide)(1H-imidazole)-ruthenate(III)), [9] KP1019 (indazolium trans-[tetrachloridobis(1H-indazole)-ruthenate(III)]), [10] and KP1339 (sodium trans-[tetrachloridobis(1H-indazole)-ruthenate(III)]) [11] are currently in phase II clinical trials. Organometallic ruthenium(II) arene Supporting information for this article is given via a link at the end of the document complexes such as [(η 6 -C 6 H 5 Ph)Ru(en)Cl][PF 6 ] (RM175, en = ethylenediamine) [12] and [(η 6 -arene)Ru(pta)Cl 2 ] (pta = 1,3,5-triaza-7-phosphatricyclo[3.3.1]decane; arene = toluene RAPTA-T; arene = p -cymene RAPTA-C) [13,14] are also showing great therapeutic promise.…”