Ru complexes containing Cp, mPTA and natural purine bases (mPTA = methyl-N-1,3,5-triaza-7-phosphaadamantane): Evaluation of their antiproliferative activity, solubility and redox properties

Hajji, Lazhar; Saraiba-Bello, Cristobal; Scalambra, Franco; Segovia-Torrente, Gaspar; Romerosa, Antonio

doi:10.1016/j.jinorgbio.2021.111404

Cited by 8 publications

(6 citation statements)

References 33 publications

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“…However, various Ru complex families are currently under investigation regarding their anticancer properties, and some RuCp piano stool complexes have shown moderate to high antiproliferative activity. These complexes often display a balance between sufficient water solubility and lipophilicity to penetrate cell membranes . Recently, heterobimetallic compounds containing RuCp fragments together with Cu or Ni have shown exceptionally high antiproliferative effects .…”

Section: Resultsmentioning

confidence: 99%

Ligand Modifications on a Cp(quinolate)Ru Catalyst to Improve Its Stability in a Bio-orthogonal Deprotection Reaction

Seefeldt,

Miller,

Heinrich

et al. 2024

Organometallics

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The deprotection or activation of substances in biological systems is of particular interest as this method can be used to activate prodrugs in a site- and time-specific manner, thus minimizing possible side effects. Investigations of the literature-known Ru catalyst [RuCp(QL)(η3-allyl)PF6] (with Cp = η-cyclopentadienide, QL= 5-(methoxycarboyl)-8-quinolinolate, 5c) revealed stability issues of the dissolved catalyst in air. We surmised that a more stable catalyst would perform better under biologically relevant conditions and that classical modifications in the ligand set would affect such improved properties. In this work, a systematic study is reported to modify the Cp ligand by using Cp* (Cp* = η-pentamethyl-cyclopentadienide), trimethylsilyl Cp, or t-butyl Cp instead and on the allyl ligand by introducing a methyl group at the middle carbon of 5c. Periodical 1H NMR measurements in DMSO-d 6 were performed to monitor the stability of the complexes for longer periods in air, and the catalytic activity of the synthesized compounds was investigated by the deprotection of an alloxycarbonyl (alloc)-protected fluorescent coumarin dye, as monitored by an increase in fluorescence intensity. Modification of the allyl ligand had no effect on the stability, but modification of the Cp ligand was shown to affect the stability of the dissolved complex and, in the case of Cp*, significantly prolong it. As expected, the more stable catalysts are catalytically active for a longer period, but as the reaction rate is not as fast, slightly lower or similar overall yields as compared to the original complex were achieved. Preliminary MTT testing of the obtained complexes revealed IC50 values in the low micromolar range.

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Section: Resultsmentioning

confidence: 99%

Ligand Modifications on a Cp(quinolate)Ru Catalyst to Improve Its Stability in a Bio-orthogonal Deprotection Reaction

Seefeldt,

Miller,

Heinrich

et al. 2024

Organometallics

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“…Extensive research has been dedicated to the exploration of ruthenium compounds as potential candidates for anticancer drugs, − and a few ruthenium complexes entered clinical trials for chemotherapy or photodynamic therapy (Figure A). − Organometallic piano-stool complexes based on the [Ru II (η 6 -arene)] core have emerged as possible alternatives to platinum-based chemotherapeutics, ,− and in particular complexes belonging to the RAPTA family have shown great promise (Figure B). − In addition, various ruthenium(II) compounds bearing a η 5 -coordinated cyclopentadienyl ligand (Cp), or its substituted derivatives, have attracted increasing attention in the medicinal field (Figure C). − Since the Cp ligand is formally anionic, the bond with the ruthenium is strengthened by an electrostatic contribution, supplying robustness to the overall structure. In the pursuit of novel and potent metallodrugs, dinuclear metal complexes could offer significant advantages compared to their corresponding monometallic counterparts. , In this regard, several complexes containing two ruthenium(II) arene fragments connected by variable linkers − and a diversity of other diruthenium species − have been evaluated, showing an interesting activity in several cases.…”

Section: Introductionmentioning

confidence: 99%

Anticancer Potential of Diruthenium Complexes with Bridging Hydrocarbyl Ligands from Bioactive Alkynols

Bresciani,

Vančo,

Funaioli

et al. 2023

Inorg. Chem.

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Diruthenacyclopentenone complexes of the general composition [Ru2Cp2(CO)2{μ–η1:η3-CHC(C(OH)(R))C(O)}] (2a–c; Cp = η5-C5H5) were synthesized in 94–96% yields from the reactions of [Ru2Cp2(CO)2{μ–η1:η3-C(Ph)C(Ph)C(O)}] (1) with 1-ethynylcyclopentanol, 17α-ethynylestradiol, and 17-ethynyltestosterone, respectively, in toluene at reflux. Protonation of 2a–c by HBF4 afforded the corresponding allenyl derivatives [Ru2Cp2(CO)3{μ–η1:η2-CHCR}]BF4 (3a–c) in 85–93% yields. All products were thoroughly characterized by elemental analysis, mass spectrometry, and IR, UV–vis, and nuclear magnetic resonance spectroscopy. Additionally, 2a and 3a were investigated by cyclic voltammetry, and the single-crystal diffraction method was employed to establish the X-ray structures of 2b and 3a. The cytotoxicity in vitro of 2b and 3a–c was evaluated against nine human cancer cell lines (A2780, A2780R, MCF-7, HOS, A549, PANC-1, Caco-2, PC-3, and HeLa), while the selectivity was assessed on normal human lung fibroblast (MRC-5). Overall, complexes exert stronger cytotoxicity than cisplatin, and 3b (comprising 17α-estradiol derived ligand) emerged as the best-performing complex. Inductively coupled plasma mass spectrometry cellular uptake studies in A2780 cells revealed a higher level of internalization for 3b and 3c compared to 2b, 3a, and the reference compound RAPTA-C. Experiments conducted on A2780 cells demonstrated a noteworthy impact of 3a and 3b on the cell cycle, leading to the majority of the cells being arrested in the G0/G1 phase. Moreover, 3a moderately induced apoptosis and oxidative stress, while 3b triggered autophagy and mitochondrial membrane potential depletion.

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“…Platinum‐phosphine complexes receive significant attention in coordination chemistry according to the high affinity of Pt for phosphorus, the stability of Pt−P bonds, and the ease of using 31 P‐NMR spectroscopy as a helpful characterization technique. Nevertheless, there are often limited studies on platinum‐phosphine complexes for pharmaceutical purposes specifically, compared to the nitrogen ligands [16–19] . As a continuation of our ongoing interest in the biological investigation of Pt(II) complexes, [20–27] herein, we designed to evaluate the anticancer activities of Pt(II) coordination complexes comprising 2‐(diphenylphosphino)pyridine (dppy) dangling/bridging ligand as one of the most attractive phosphine compounds which plays a vital role in coordination and organometallic chemistry, and exhibit various physical or chemical properties according to the presence of different coordination modes [28,29] .…”

Section: Introductionmentioning

confidence: 99%

“…Nevertheless, there are often limited studies on platinumphosphine complexes for pharmaceutical purposes specifically, compared to the nitrogen ligands. [16][17][18][19] As a continuation of our ongoing interest in the biological investigation of Pt(II) complexes, [20][21][22][23][24][25][26][27] herein, we designed to evaluate the anticancer activities of Pt(II) coordination complexes comprising 2-(diphenylphosphino)pyridine (dppy) dangling/bridging ligand as one of the most attractive phosphine compounds which plays a vital role in coordination and organometallic chemistry, and exhibit various physical or chemical properties according to the presence of different coordination modes. [28,29] Hence, a series of Pt(II) coordination complexes with a general formula of (cis-PtL 2 X 2 ), L = dppy and X=Cl, Me [30,31] and p-tolyl [31] were biologically investigated to have antitumor properties.…”

Section: Introductionmentioning

confidence: 99%

ROS‐Mediated Antitumor Activity, Apoptosis, and Molecular Docking Studies of Platinum(II) Coordination Complexes Bearing 2‐(Diphenylphosphino)pyridine Ligands

Mojaddami

Abedanzadeh

Bagherzadeh

et al. 2023

Chemistry & Biodiversity

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Platinum-based drugs have been widely used in cancer treatment. However, their severe side effects have limited their use. So, researchers have been striving to find compounds with fewer side effects and greater efficacy, to overcome these drawbacks. Here, the cytotoxicity of platinum(II) complexes containing 2-(diphenylphosphino)pyridine ligands have been studied on human lung (A549), ovarian (SKOV3), breast (MCF-7) cancer, and normal breast (MCF-10A) cell lines. The most potent compound exhibits a marked cell growth-inhibitory effect against ovarian and lung cancer cells with IC 50 values of 9.41 and 5.58 μM, respectively, which were significantly better than that observed for cisplatin (19.02, and 8.64 μM). Additionally, all complexes achieved significantly lower cytotoxicity towards MCF-10A. To investigate the interaction of complexes with DNA, an electrophoresis mobility shift assay was conducted, which indicated that complexes bind to DNA and affect its electrophoretic mobility. An analysis of apoptosis in A549 cells supported the conclusion that they inhibits cell proliferation via induction of apoptosis in a concentration-dependent manner. Molecular docking was also used to investigate the interactions of compounds with different DNA structures. These compounds have the ability to be a suitable pharmaceutical compound with further investigations in the field of cancer research.

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Ru complexes containing Cp, mPTA and natural purine bases (mPTA = methyl-N-1,3,5-triaza-7-phosphaadamantane): Evaluation of their antiproliferative activity, solubility and redox properties

Cited by 8 publications

References 33 publications

Ligand Modifications on a Cp(quinolate)Ru Catalyst to Improve Its Stability in a Bio-orthogonal Deprotection Reaction

Ligand Modifications on a Cp(quinolate)Ru Catalyst to Improve Its Stability in a Bio-orthogonal Deprotection Reaction

Anticancer Potential of Diruthenium Complexes with Bridging Hydrocarbyl Ligands from Bioactive Alkynols

ROS‐Mediated Antitumor Activity, Apoptosis, and Molecular Docking Studies of Platinum(II) Coordination Complexes Bearing 2‐(Diphenylphosphino)pyridine Ligands

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