Potential of cycloaddition reactions to generate cytotoxic metal drugs in vitro

Murray, Benjamin S.; Crot, Stéphanie; Siankevich, Sviatlana; Dyson, Paul J.

Abstract

Severe general toxicity issues blight many chemotherapeutics utilized in the treatment of cancers, resulting in the need for more selective drugs able to exert their biological activity at only the required location(s). Toward this aim, we report the development of an organometallic ruthenium compound, functionalized through a η6-bound arene ligand with a bicyclononyne derivative, able to participate in strain-promoted cycloaddition reactions with tetrazines. We show that combination of the ruthenium compound with a ditetrazine in biological media results in the in situ formation of a dinuclear molecule that is more cytotoxic toward cancer cells than the starting mononuclear ruthenium compound and tetrazine components. Such an approach may be extended to in vivo applications to construct a cytotoxic metallodrug at a tumor site, providing a novel approach toward the turn-on cytotoxicity of metallodrugs in the treatment of cancer.

Citation

Murray, B. S., Crot, S., Siankevich, S., & Dyson, P. J. (2014). Potential of cycloaddition reactions to generate cytotoxic metal drugs in vitro. Inorganic chemistry, 53(17), 9315-9321. https://doi.org/10.1021/ic501438k

• Acceptance Date: Jun 17, 2014
• Online Publication Date: Aug 18, 2014
• Publication Date: Sep 2, 2014
• Deposit Date: Oct 8, 2015
• Publicly Available Date: Nov 23, 2017
• Journal: Inorganic chemistry
• Print ISSN: 0020-1669
• Publisher: American Chemical Society
• Peer Reviewed: Peer Reviewed
• Volume: 53
• Issue: 17
• Pages: 9315-9321
• DOI: https://doi.org/10.1021/ic501438k
• Keywords: Cycloaddition reactions; Cytotoxic metal drugs; Cancer drugs
• Public URL: https://hull-repository.worktribe.com/output/379538
• Publisher URL: http://pubs.acs.org/doi/abs/10.1021/ic501438k
• Additional Information: This document is the Accepted Manuscript version of a Published Work that appeared in final form in Inorganic chemistry, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see http://dx.doi.org/10.1021/ic501438k.
• Contract Date: Nov 23, 2017