Synthesis and In Vitro (Anticancer) Evaluation of η6-Arene Ruthenium Complexes Bearing Stannyl Ligands

Renier, Olivier; Deacon-Price, Connor; Peters, Joannes E. B.; Nurekeyeva, Kunsulu; Russon, Catherine; Dyson, Simba; Ngubane, Siyabonga; Baumgartner, Judith; Dyson, Paul J.; Riedel, Tina; Chiririwa, Haleden; Blom, Burgert

doi:10.3390/inorganics5030044

Cited by 14 publications

(5 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…One of the causes that leads to low toxicity of these compounds is the lack of lipophilic groups, decreasing the cellular uptake of these complexes. 33,51,52 To investigate the effects on cell morphology of the most selective compound, complex 1 was incubated with the MDA-MB-231 cells at different concentrations ( Figure S23 of SI section) proportional to the IC 50 values. Negative control cells have a spindle-shaped phenotype in both strains, while cells treated with complex 1, especially at 24 μM for MDA-MB-231 (2 × IC 50 , 24 h), have spherically shaped cells (which may be indicative of apoptosis), 33,[53][54][55][56][57] in addition to damaged cell bodies, ongoing cell death, loss of adhesion and confluence.…”

Section: Biological Anticancer Experimentsmentioning

confidence: 99%

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

Honorato¹,

Oliveira²,

Leite³

et al. 2020

J. Braz. Chem. Soc.

View full text Add to dashboard Cite

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.

show abstract

Section: Biological Anticancer Experimentsmentioning

confidence: 99%

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

Honorato¹,

Oliveira²,

Leite³

et al. 2020

J. Braz. Chem. Soc.

View full text Add to dashboard Cite

show abstract

“…The anticancer or biological activity investigations of any of these four classes of compounds or elucidations of their bonding nature by theoretical methods have not previously been evaluated. Moreover, given our previous numerous studies on ruthenium arene stannyl and stannate complexes, as well as their germanium analogues, ,, the extension to osmium is expected to yield different biological activities given the rather inert nature of Os(II) vs Ru(II) (see above). This hence motivated us to explore the analogous osmium chemistry with a view of biological anticancer applications, not as a mere extension from Ru, but expecting different in vitro biological activities compared to analogous ruthenium complexes.…”

Section: Introductionmentioning

confidence: 99%

“…We have reported a series of neutral ruthenium-based germyl ([Ru]−GeCl 3 ) and stannyl ([Ru]−SnCl 3 ) complexes that displayed less than optimal cytotoxic activity on numerous cell lines in vitro (Scheme 1). 13,15 In contrast, ruthenium germanate and stannate salt complexes displayed potent and promising cytotoxic activity on two breast cancer cell lines (MCF-7 and MDA-MB-231) and good selectivity, suggesting that the ionic nature of the complexes influences their biological effects. 14 Osmium, as a heavier analogue of ruthenium, might be expected to be a suitable metal for anticancer applications; however, when compared to ruthenium, research into osmiumbased anticancer agents is less pronounced.…”

Section: Introductionmentioning

confidence: 99%

Osmium Arene Germyl, Stannyl, Germanate, and Stannate Complexes as Anticancer Agents

et al. 2021

Self Cite

View full text Add to dashboard Cite

Herein, we describe the synthesis, full spectroscopic characterization, DFT (density functional theory) calculations, and single-crystal X-ray diffraction analyses of a series of osmium arene σ-germyl, germanate, σ-stannyl, and stannate complexes, along with their cytotoxic (anticancer) investigations. The known dimer complexes [OsCl2(η6-C6H6)]2 (1) and [OsCl2(η6-p-cymene)]2 (2) were reacted with PPh3 to form the known mononuclear complex [OsCl2(η6-p-cymene)(PPh3)] (3) and the new complex [OsCl2(η6-C6H6)(PPh3)] (6); complex 3 was reacted with GeCl2·(dioxane) and SnCl2 to afford, by insertion into the Os–Cl bond, the neutral σ-germyl and stannyl complexes [OsCl(η6-p-cymene)(PPh3)(GeCl3)] (7) and [OsCl(η6-p-cymene)(PPh3)(SnCl3)] (11), respectively, as a mixture of enantiomers. Similarly, the reaction of complex 6 with GeCl2·(dioxane) afforded [OsCl(η6-C6H6)(PPh3)(GeCl3)] (9). Complex 2, upon reaction with 1,1-bis(diphenylphosphino)methane (dppm), formed a mixture of [OsCl2(η6-p-cymene)(κ1-dppm)] (4) and [Os(η6-p-cymene)(κ2-dppm)Cl]+Cl– (5) when prepared in acetonitrile and a mixture of 4 and the dinuclear complex [[OsCl2(η6-p-cymene)]2(μ-dppm)] (0) when prepared in dichloromethane. By utilizing either isolated 4 or a mixture of 4 and 5, the synthesis of κ2-dppm germanate and stannate salts, [OsCl(η6-p-cymene)(κ2-dppm)]+GeCl3 – (8) and [OsCl(η6-p-cymene)(κ2-dppm)]+SnCl3 – (10), were accomplished via halide-abstracting reactions with GeCl2·(dioxane) or SnCl2, respectively. All resulting complexes were characterized by means of multinuclear NMR, FT-IR, ESI-MS, and UV/Vis spectroscopy. X-ray diffraction analyses of 4, 8, 9, 10, and 11 were performed and are reported. DFT studies (B3LYP, basis set LANL2DZ for Os, and def2-TZVPP for Sn, Ge, Cl, P, C, and H) were performed on complex 9 and the benzene analogue of complex 11, 11–benzene, to evaluate the structural changes and the effects on the frontier molecular orbitals arising from the substitution of Ge for Sn. Finally, complexes 3 and 7–11 were investigated for potential anticancer activities considering cell cytotoxicity and apoptosis assays against Dalton’s lymphoma (DL) and Ehrlich ascites carcinoma (EAC) malignant cancer cell lines. The complexes were also tested against healthy peripheral blood mononuclear cells (PBMCs). All cell lines were also treated with the reference drug cisplatin to draw a comparison with the results obtained from the reported complexes. The study was further corroborated with in silico molecular interaction simulations and a pharmacokinetic study.

show abstract

“…Goitia and co-workers have reported that gold(I)/complex with 2-thiouracil exhibits excellent cytotoxic activity against PC-12 and NIH-3T3 cell lines . Thus, having in mind that Ru(II) complexes have been investigate in the development of compounds with anticancer properties, to evaluate the structural modification on biological properties of ruthenium complexes with 2-thiouracil derivatives, we present here the synthesis of two new monocationic complexes, expecting that they will have good cytotoxicity against cancer cells. − …”

Section: Introductionmentioning

confidence: 99%

Nucleobase Derivatives as Building Blocks to Form Ru(II)-Based Complexes with High Cytotoxicity

et al. 2020

View full text Add to dashboard Cite

Two new Ru(II)-based complexes containing 2-thiouracil derivatives, known as 2-thiouracil (2TU) and 6-methyl-2-thiouracil (6m2TU), were synthesized using cis,trans-[RuCl2(PPh3)2(bipy)] as a precursor. The obtained compounds with a general formula trans-[Ru(2TU)(PPh3)2(bipy)]PF6 (1) and trans-[Ru(6m2TU)(PPh3)2(bipy)]PF6 (2) were characterized by analytical techniques such as NMR, UV–vis, and IR spectroscopies, elementary analysis, mass spectrometry, and single-crystal X-ray diffraction. Moreover, the investigation of the complexes–DNA interaction were carried out using spectrophotometric titrations and showed that the complexes present a weak interaction with this biomolecule. The compounds were evaluated against HL-60, K-562, HepG2, and B16-F10 cancer cells and against noncancer cells (PBMCs). The results of the biological assay revealed that complex 2 is more promising than complex 1. Finally, the present study suggests that complexes 1 and 2 causes cell death by apoptosis, significantly increasing the percentage of apoptotic HL-60 cells, in which the compounds altered the cell cycle, reducing the cells in G1/G0, G2/M, and S phases.

show abstract

Synthesis and In Vitro (Anticancer) Evaluation of η6-Arene Ruthenium Complexes Bearing Stannyl Ligands

Cited by 14 publications

References 43 publications

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

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

Osmium Arene Germyl, Stannyl, Germanate, and Stannate Complexes as Anticancer Agents

Nucleobase Derivatives as Building Blocks to Form Ru(II)-Based Complexes with High Cytotoxicity

Contact Info

Product

Resources

About