In vivo tumour and metastasis reduction and in vitro effects on invasion assays of the ruthenium RM175 and osmium AFAP51 organometallics in the mammary cancer model

Bergamo, Alberta; Masi, Alessia De; Peacock, Anna F. A.; Habtemariam, Abraha; Sadler, Peter J.; Sava, Gianni

doi:10.1016/j.jinorgbio.2009.10.005

Cited by 164 publications

(143 citation statements)

References 31 publications

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“…A study evaluating the biological potencies of two piano-stool complexes of the same overall ligand set that differ only in the metal ( Figure 17) showed that ruthenium seems to play a key role in anti-metastatic activity. 117 Although the Os II complex AFAP51 is more active against breast cancer cells in vitro, the Ru II compound RM175 (vide infra) has in vivo activity against a mammary carcinoma and also reduced metastasis. 117 Although its in vitro toxicity against cancer cells is low, RM 175 is active against in vivo human ovarian and non-small cell lung cancer models.…”

Section: Structural Switches -Activation By Hydrolysismentioning

confidence: 99%

Designing organometallic compounds for catalysis and therapy

et al. 2012

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Section: Structural Switches -Activation By Hydrolysismentioning

confidence: 99%

Designing organometallic compounds for catalysis and therapy

et al. 2012

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“…2,3 For example, Jaouen et al have designed ferricenium complexes which target hormone receptors in breast cancer cells, 4 certain Ru II arene complexes are active in vitro and in vivo, [5][6][7] , 8 and a few reports of anticancer active organometallic osmium complexes have recently appeared. [9][10][11][12][13][14][15] Osmium complexes are often considered to be relatively inert (a common characteristic of low-spin d 6 metal ions and especially 3 rd row transition metals). 16,17 Organometallic Os II and Ru II arene complexes can adopt very similar threedimensional structures.…”

Section: Introductionmentioning

confidence: 99%

Structure–activity relationships for organometallic osmium arene phenylazopyridine complexes with potent anticancer activity

Habtemariam

Basri

et al. 2011

Dalton Trans.

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We report the synthesis and characterisation of 32 half sandwich phenylazopyridine Os II arene complexes [Os(h 6 -arene)(phenylazopyridine)X] + in which X is chloride or iodide, the arene is p-cymene or biphenyl and the pyridine and phenyl rings contain a variety of substituents (F, Cl, Br, I, CF 3 , OH or NO 2 ). Ten X-ray crystal structures have been determined. Cytotoxicity towards A2780 human ovarian cancer cells ranges from high potency at nanomolar concentrations to inactivity. In general the introduction of an electron-withdrawing group (e.g. F, Cl, Br or I) at specific positions on the pyridine ring significantly increases cytotoxic activity and aqueous solubility. Changing the arene from p-cymene to biphenyl and the monodentate ligand X from chloride to iodide also increases the activity significantly. Activation by hydrolysis and DNA binding appears not to be the major mechanism of action since both the highly active complex [Os(h 6 -bip)(2-F-azpy)I]PF 6 (9) and the moderately active complex [Os(h 6 -bip)(3-Cl-azpy)I]PF 6 ( 23) are very stable and inert towards aquation. Studies of octanol-water partition coefficients (log P) and subcellular distributions of osmium in A2780 human ovarian cancer cells suggested that cell uptake and targeting to cellular organelles play important roles in determining activity. Although complex 9 induced the production of reactive oxygen species (ROS) in A2780 cells, the ROS level did not appear to play a role in the mechanism of anticancer activity. This class of organometallic osmium complexes has new and unusual features worthy of further exploration for the design of novel anticancer drugs.

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“…6 The introduction of XY = azopyridine, a strong π-acceptor, as the N,N-chelating ligand has a remarkable effect on the reactivity, especially when Z = 8 We have now investigated the activity of this complex in vivo versus HCT116 human colon cancer xenografts and the distribution of osmium in plasma and tissues. Further insight into the mechanism of action of 1 was obtained from studies of its redox potential, its ability to 4 generate Reactive Oxygen Species (ROS) in cells, and the ability of L-buthioninesulfoximine (L-BSO), a specific inhibitor of γ-glutamyl-cysteine synthetase known to reduce intracellular thiol levels, 9 to enhance the cytotoxicity of the complex.…”

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confidence: 99%