Combining [Arene–Ru] with Azocarboxamide to Generate a Complex with Cytotoxic Properties

Abstract

Azocarboxamide (azcH) has been combined for the first time with [Ru-Cym] to generate metal complexes with N,N- and N,O-coordination mode, [(Cym)Ru(azc)Cl] and [(Cym)Ru(azcH)Cl](+) [PF6 ](-). Geometric and electronic structures of the complexes are reported along with their in vitro activities against different tumour cell lines and preliminary results on solution chemistry. Compound [(Cym)Ru(azc)Cl] exhibited remarkable cytotoxic properties. It was cell-type specific and had comparable IC50 values towards both cancer cells and their drug-resistant subline. A tenfold increase in the sensitivity towards [(Cym)Ru(azc)Cl] was noted for the tumour cells with depleted intracellular glutathione (GSH) level, suggesting the essential role of GSH in cell response to this compound.

Synthesis and X-ray Structural Analysis of the Ruthenium(III) Complex Na[trans-RuCl4(DMSO) (PyrDiaz)], the Diazene Derivative of Antitumor NAMI-Pyr

“…31 Combining complex 2 with an excess of ligand 1 in acetone solution resulted in displacement of one dimethyl sulfoxide ligand in the ruthenium coordination sphere and the formation of a new compound 3 shown in Scheme 3 (left). In contrast to our previous findings 19,20 for arene-ruthenium(II) compounds from Figure 2, in complex 3 diazene moiety did not participate in coordination to the metal centre. Instead, the pyridine part of the molecule replaced one axial dimethyl sulfoxide ligand.…”

“…18 Redox-active diazenecarboxamides were also combined with organometallic [Ru(II)-Arene] to generate complexes with interesting coordination modes and chemical reactivity ( Figure 2). 19,20 In the context of our endeavour in the field of potential anti-cancer agents, complex B was identified as highly cytotoxic against tumour cell lines with IC 50 values in the low micro-molar range. 19,21 ure 3), we were prompted to examine the coordination ability of diazenedicarboxamide N 1 -(4-isopropylphenyl)-N 2 -(pyridin-2-ylmethyl)diazene-1,2-dicarboxamide (1) (Scheme 1).…”

“…19,20 In the context of our endeavour in the field of potential anti-cancer agents, complex B was identified as highly cytotoxic against tumour cell lines with IC 50 values in the low micro-molar range. 19,21 ure 3), we were prompted to examine the coordination ability of diazenedicarboxamide N 1 -(4-isopropylphenyl)-N 2 -(pyridin-2-ylmethyl)diazene-1,2-dicarboxamide (1) (Scheme 1). Compound 1 has been previously screened for anti-cancer activity.…”

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

“…The downfield =NOH proton region showed four broad signals of relative intensities 1:1:1.7:0.8, which could be tentatively assigned to the =NOH proton resonances of four different diastereomers. Having in mind the possible formation of four different diastereomers, as well as the potential κ 2 N,N,N/κ 3 N,N,N coordination of the 2-picolylamino-oxime ligand that could produce mono and/or dicationic ruthenium compounds,[8,46] we carried out the reaction in the presence of TlPF 6 (Scheme 2). The reaction proceeds in two hours at room temperature to afford a brown suspension, from which a brown solid residue can be extracted with THF or acetone.…”

“…[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.…”