“Half-Sandwich”/RuII Anticancer Complexes Containing Triphenylphosphine and p-Substituted Benzoic Acids

Abstract

Mononuclear and binuclear Ru II /arene/triphenylphosphine complexes with p-substituted benzoic acid derivatives were prepared and characterized. These monocationic complexes of type [Ru(η 6-p-cymene)(PPh 3)L] (L = benzoic acid (1), p-hydroxybenzoic acid (2), p-nitrobenzoic acid (3) and terephthalic acid (4)) were characterized using various techniques, such as nuclear magnetic resonance (NMR) and matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) mass spectrometry, and the crystal structure of 1, 3 and 4 were determined by X-ray diffraction analysis. The cytotoxicity of the complexes was evaluated, in vitro, against tumorigenic [MDA-MB-231, MCF-7 (breast), A549 (lung) and DU-145 (prostate)] and non-tumorigenic [MCF-10A (breast), MRC-5 (lung) and PNT-2 (prostate)] cells. The binuclear complex (4) was inactive due to its low solubility. Complexes 1, 2 and 3 showed similar cytotoxicity, however, complex 1 presented better selectivity index against MDA-MB-231 than compounds 2 and 3. Cellular ruthenium absorption was explored by inductively coupled plasma mass spectrometry (ICP-MS) analyzing the whole cells and the culture medium. Complementary studies showed that complex 1 inhibited colony formation, induced morphology changes in cells and promoted cell cycle arrest in the Sub-G1 phase for the MDA-MB-231 cells.

Frustrated and Realized Hydrogen Bonding in 4-Hydroxy-3,5-ditertbutylphenylphosphine Derivatives

“…All synthesized compounds (Scheme 1) were fully characterized by melting point and 1D and 2D NMR spectroscopy. 1 H, 31 P, 13 C, 1 H− 1 H gCOSY, 1 H− 13 C gHSQC, and 1 H− 13 C gHMBC NMR spectra are in full agreement with the structures shown (see Experimental Section and the Supporting Information for full details). Synthesis of the reagent 2,6-ditertbutyl-4-bromophenoxy-trimethylsilane, used as a precursor in the synthesis of phosphines 1 and 3, was recently optimized, and its crystal structure was reported.…”

New Heteroleptic RuII/Diphosphine Complexes with Cytotoxicity against Human Breast and Murine Ascitic Sarcoma 180 Tumor Cells

“…Water-n-octanol partition coefficients were determined using the stir flask method, as previously described. 8…”

“…3 Recently, a great number of ruthenium complexes containing different ligands, have been tested as antitumor agents against different kinds of tumor cell lines, showing to be very active. [4][5][6][7][8][9] Thus, picolinate containing complex [Ru(η 6 -p-cymene)Cl(picolinate)] is active against HeLa (drug concentration at which 50% of the cells are viable relative to the control (IC 50 ) = 82.0 μM) and human melanoma cells (FemX, IC 50 = 36.2 μM). 10 The possible reason for this behavior is that the [Ru(η 6 -p-cymene) Cl(picolinate)] accumulates in the deoxyribonucleic acid (DNA) molecule, since it has high affinity for DNA-binding.…”

Organoruthenium (II) complexes featuring pyrazole‐linked thiosemicarbazone ligands: Synthesis, DNA/BSA interactions, molecular docking, and cytotoxicity studies

“…[21] XRD studies of the binuclear Ru(II)-arene-triphenylphosphine complex with terephthalic acid as bridging ligand were carried by Honorato et al The bidentate O-O coordination mode of the carboxylate groups was unambiguously confirmed by the X-ray technique. [22] This paper reports the design, synthesis, and biological investigation of novel binuclear ruthenium (II)-arene complexes (C1-C8) containing pyrazole substituted thiosemicarbazone ligands (L1-L4).…”

“…[ 21 ] XRD studies of the binuclear Ru(II)‐arene‐triphenylphosphine complex with terephthalic acid as bridging ligand were carried by Honorato et al The bidentate O–O coordination mode of the carboxylate groups was unambiguously confirmed by the X‐ray technique. [ 22 ]…”