Rhenium Complexes with Visible‐Light‐Induced Anticancer Activity

Abstract

Metal complexes constitute an attractive class of compounds for applications in medicinal chemistry and chemical biology due to features such as unusual reactivities, tunable ligand exchange kinetics, stereochemical diversity, structural complexity, the availability of radioisotopes, and distinct physicochemical properties. [1] However, it is remarkable that although the discovery of the antiproliferative activity of cis-[PtCl 2 (NH 3) 2 ] dates back almost half a century, [2] cisplatin and its derivatives remain the most important metal-based anticancer drugs used in the clinic at the present day. [3] In the quest for a new generation of metal-containing anticancer agents we here wish to report a class of rhenium(I) complexes as highly potent visible-light-triggered anticancer organometallics. We discovered that rhenium(I) indolato complexes 1-3 provoke a strong light-induced antiproliferative activity in cancer cells (Figure 1). This is unexpected since the related class of rhenium(I) tricarbonyl polypyridine complexes (e.g. 4) are well-established nontoxic luminescent probes routinely applied for biological imaging. [4] Thus, replacing just the 2,2′bipyridine in 4 for 2-(2′-pyridyl)indolato and its derivatives (1-3) completely changes the physicochemical and biological properties of such rhenium(I) complexes by abolishing luminescence and instead causing light-induced anticancer activity. [5] Figure 2 displays the structure of a benzylated derivative of rhenium(I) complex 1 in which rhenium is coordinated in a bidentate fashion to a pyrido[2,3-a]pyrrolo

Developing strategies to predict photodynamic therapy outcome: the role of melanoma microenvironment

“…Previously, they demonstrated that this compound provoked a strong light-induced antiproliferative activity in cancer cells in vitro. Although drug concentration was five times greater than that for in vitro studies, phototoxicity was suppressed when treatment was applied on spheroids, especially in those layers found in the core of the spheroid [63] (Table 2). In addition, Barbugli and colleagues studied PDT efficiency using chloroaluminum phthalocyanine (ClAlPc) liposomes on 3D cultures.…”

“…Development of 3D in vitro platform to evaluate the efficiency of photodynamic treatment retained melanoma architecture and tumor cell-tumor cell and tumor ECM-cell interactions [63]. After a comprehensive review of the literature, we suggest that new complementary in vitro tools and platforms are required to better predict the outcome of PDT on patients.…”

Re(I) carbonyl complexes: Multimodal platforms for inorganic chemical biology

“…In both cases, the complexes were incubated on HeLa cells and were found cytotoxic after irradiation only, with IC 50 in the nanomolar range. In addition, cytotoxicity of one of the complexes was also shown in 3D models: melanoma spheroids incubated with the complex and irradiated displayed cell death and loss of spheroid integrity at their edges [71]. As discussed later in this review (Section 2.2), Gasser et al also designed Re(CO) 3 complexes and peptide conjugates for PDT [73].…”

“…Some of these complexes could even be embedded in a flexible polymeric silesquioxane (SSO) film while retaining their photophysical features, which opens up the possibility to use such films as biological or microbial-photoinactivating surfaces [70]. The Meggers' group designed complex 16 ( Figure 8) and tuned the N^N and the R 1 ligands in order to be able to irradiate the complexes with either visible light [71] or red-light [72]. In both cases, the complexes were incubated on HeLa cells and were found cytotoxic after irradiation only, with IC 50 in the nanomolar range.…”

Underestimated Potential of Organometallic Rhenium Complexes as Anticancer Agents

“…43,44,46,47 Most of them act as photodynamic therapy (PDT) photosensitizers (PS) -i.e. they transfer the energy received from light to oxygen (present in tissues) to generate reactive oxygen species (ROS).…”