Yes / Ruthenium compounds have been shown to be promising alternatives to platinum(II) drugs. However, their clinical success depends on achieving mechanisms of action that overcome Pt-resistance mechanisms. Electron-deficient organoruthenium complexes are an understudied class of compounds that exhibit unusual reactivity in solution and might 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 cell 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 non-small cell lung cancer xenograft model hints at the 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 promise as anticancer drug candidates. / UF150295/Royal Society; University of Bradford; Government Department of Business, Energy and Industrial Strategy; SBF003\1170/British Heart Foundation Springboard Award; AMS_/Academy of Medical Sciences/United Kingdom
| Identifer | oai:union.ndltd.org:BRADFORD/oai:bradscholars.brad.ac.uk:10454/18025 |
| Date | 04 September 2020 |
| Creators | Soldevila-Barreda, Joan J., Azmanova, Maria, Pitto-Barry, Anaïs, Cooper, Patricia A., Shnyder, Steven, Barry, Nicolas P.E. |
| Source Sets | Bradford Scholars |
| Language | English |
| Detected Language | English |
| Type | Article, Accepted manuscript |
| Rights | © 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim. This is the peer-reviewed version of the following article: Soldevila-Barreda JJ, Azmanova M, Pitto-Barry A et al (2020) Preclinical Anticancer Activity of an Electron-Deficient Organoruthenium(II) Complex. ChemMedChem. xxx, which has been published in final form at https://doi.org/10.1002/cmdc.202000096. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving., Unspecified |
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