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Issue 24, 2015
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Design, synthesis and characterisation of new chimeric ruthenium(ii)–gold(i) complexes as improved cytotoxic agents

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Abstract

Two heterobimetallic complexes, i.e. [RuCl2(p-cymene)(μ-dppm)AuC] (1) and [RuCl2(p-cymene)(μ-dppm)Au(S-thiazoline)] (3), based on known cytotoxic [Ru(p-cymene)Cl2(PR3)] and [AuX(PR3)] (X = Cl, SR) molecular scaffolds, with the diphosphane linker 1,1-bis(diphenylphosphino)methane, dppm, were conveniently prepared and characterised. Remarkably, the new compounds manifested a more favourable in vitro pharmacological profile toward cancer cells than individual ruthenium and gold species being either more cytotoxic or more selective. The interactions of the studied compounds with (pBR322) DNA and their inhibitory effects on cathepsin B were also assessed. In addition, their reactivity toward suitable models of protein targets was explored and clear evidence gained for disruption of the bimetallic motif and for protein binding of monometallic fragments. Overall, the data reported here strongly support the concept of multifunctional heterometallic compounds as “improved” candidate agents for cancer treatment. The mechanistic and pharmacological implications of the present findings are discussed.

Graphical abstract: Design, synthesis and characterisation of new chimeric ruthenium(ii)–gold(i) complexes as improved cytotoxic agents

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Supplementary files

Article information


Submitted
25 Mar 2015
Accepted
05 May 2015
First published
05 May 2015

Dalton Trans., 2015,44, 11067-11076
Article type
Paper
Author version available

Design, synthesis and characterisation of new chimeric ruthenium(II)–gold(I) complexes as improved cytotoxic agents

L. Massai, J. Fernández-Gallardo, A. Guerri, A. Arcangeli, S. Pillozzi, M. Contel and L. Messori, Dalton Trans., 2015, 44, 11067
DOI: 10.1039/C5DT01614B

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