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Potential of cycloaddition reactions to generate cytotoxic metal drugs in vitro

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

Authors

Stéphanie Crot

Sviatlana Siankevich

Paul J. Dyson

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.

Publication Date Sep 2, 2014
Journal Inorganic chemistry
Print ISSN 0020-1669
Electronic ISSN 1520-510X
Publisher American Chemical Society
Peer Reviewed Peer Reviewed
Volume 53
Issue 17
Pages 9315-9321
Institution 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
DOI https://doi.org/10.1021/ic501438k
Keywords Cycloaddition reactions; Cytotoxic metal drugs; Cancer drugs
Publisher URL http://pubs.acs.org/doi/abs/10.1021/ic501438k
Copyright Statement ©2015 University of Hull
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.

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