Article Dans Une Revue ChemMedChem Année : 2019

Anticancer Activity of Electron‐Deficient Metal Complexes against Colorectal Cancer in vitro Models

Maria Azmanova
Rianne M Lord
Anaïs Pitto-Barry
Nicolas P E Barry
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Résumé

Ruthenium compounds have shown to be promising alternatives to platinum(II) drugs. However, their clinical success depends on achieving mechanisms of action that overcome Ptresistance mechanisms. Electron-deficient organoruthenium complexes are an understudied class of compounds which exhibit unusual reactivity in solution and may offer novel anticancer mechanisms of action. Here, we evaluate the in vitro and in vivo anticancer properties of the electron-deficient organoruthenium complex [(p-cymene)Ru(maleonitriledithiolate)]. This compound is found to be highly cytotoxic: 5 to 60 times more potent than cisplatin towards ovarian (A2780 and A2780cisR), colon (HCT116 p53+/+ and HCT116 p53-/-), and non-small lung H460 cancer cell lines. It shows no cross-resistance and is equally cytotoxic to both A2780 and A2780cisR cell lines. Furthermore, unlike cisplatin, the remarkable in vitro antiproliferative activity of this compound appears to be p53-independent. In vivo evaluation in the hollow fibre assay across a panel of cancer cell types and subcutaneous H460 nonsmall cell lung cancer xenograft model hints at activity of the complex. Although the impressive in vitro data are not fully corroborated by the in vivo follow-up, this work is the first preclinical study of electron-deficient half-sandwich complexes and highlights their promises as anticancer drug candidates.

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hal-03379599 , version 1 (19-10-2021)

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Maria Azmanova, Joan J Soldevila-Barreda, Hira Bani Hani, Rianne M Lord, Anaïs Pitto-Barry, et al.. Anticancer Activity of Electron‐Deficient Metal Complexes against Colorectal Cancer in vitro Models. ChemMedChem, In press, 14 (22), pp.1887-1893. ⟨10.1002/cmdc.201900528⟩. ⟨hal-03379599⟩
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