Organometallic Rhenium Complexes Divert Doxorubicin to the Mitochondria

Abstract

Doxorubicin, aw ell-established chemotherapeutic agent, is knownt oa ccumulate in the cell nucleus.B yu sing ICP-MS,w es how that the conjugation of two small organometallic rhenium complexes to this structural motif results in as ignificant redirection of the conjugates from the nucleus to the mitochondria. Despite this relocation, the two bioconjugates display excellent toxicity toward HeLa cells.Inaddition, we carried out ap reliminarily investigation of aspects of cytotoxicity and present evidence that the conjugates disrupt the mitochondrial membrane potential, are strong inhibitors of human Topoisomerase II, and induce apoptosis.S uch derivatives may enhance the therapeutic index of the aggressive parent drug and overcome drug resistance by influencing nuclear and mitochondrial homeostasis.

A Rhenium Isonitrile Complex Induces Unfolded Protein Response‐Mediated Apoptosis in Cancer Cells

“…In this context, our group has been exploring the anticancer activity of polypyridyl rhenium(I) tricarbonyl complexes . Certain members of this class of compounds exhibit potent cytotoxic activity, which can be leveraged for their use as anticancer agents . Here, we describe our investigation of a new rhenium(I) tricarbonyl complex bearing a chelating polypyridyl ligand and an axial isonitrile ligand as a potent anticancer agent.…”

Bifunctional chelators for radiorhenium: past, present and future outlook

“…23,145 These ligands are able to be introduced via dissociative exchange with the three labile water molecules on the precursor, while the three faciallycoordinated CO ligands are tightly held. 16,32,147 Monodentate, bidentate and tridentate ligands have been used to create stable complexes with the rhenium(I) tricarbonyl core, 142,[148][149][150] with complexation of the core to a biomolecule-linked chelator being a favourable reaction in the field of nuclear medicine. 23 The "2 + 1"chelator approach for the [ 186/188 Re][Re(CO) 3 ] + core While monodentate ligands are robust and coordinate efficiently, they are not versatile and may coordinate more than one biomolecule to the metal centre.…”

“…23,145 These ligands are able to be introduced via dissociative exchange with the three labile water molecules on the precursor, while the three facially-coordinated CO ligands are tightly held. 16,32,147 Monodentate, bidentate and tridentate ligands have been used to create stable complexes with the rhenium( i ) tricarbonyl core, 142,148–150 with complexation of the core to a biomolecule-linked chelator being a favourable reaction in the field of nuclear medicine. 23…”

Using hydrazine to link ferrocene with Re(CO)3: A modular approach

“…Accordingly, much work has focused on the covalent attachment of organometallic fragments to other molecules to produce conjugate compounds, which continues in the recent literature [5–8]. For example, over the past few decades there has been increasing interest in the linking of organometallic compounds to molecules of biological interest [9–11].…”