Design of Rhenium Compounds in Targeted Anticancer Therapeutics

Abstract

Background: Many rhenium (Re) complexes with potential anticancer properties have been synthesized in the recent years with the aim to overcome the clinical limitations of platinum agents. Re(I) tricarbonyl complexes are the most common but Re compounds with higher oxidation states have also been investigated, as well as hetero-metallic complexes and Re-loaded self-assembling devices. Many of these compounds display promising cytotoxic and phototoxic properties against malignant cells but all Re compounds are still at the stage of preclinical studies. Methods: The present review focused on the rhenium based cancer drugs that were in preclinical and clinical trials were examined critically. The detailed targeted interactions and experimental evidences of Re compounds reported by the patentable and non-patentable research findings used to write this review. Results: In the present review, we described the most recent and promising rhenium compounds focusing on their potential mechanism of action including, phototoxicity, DNA binding, mitochondrial effects, oxidative stress regulation or enzyme inhibition. Many ligands have been described that modulating the lipophilicity, the luminescent properties, the cellular uptake, the biodistribution, and the cytotoxicity, the pharmacological and toxicological profile. Conclusion: Re-based anticancer drugs can also be used in targeted therapies by coupling to a variety of biologically relevant targeting molecules. On the other hand, combination with conventional cytotoxic molecules, such as doxorubicin, allowed to take into profit the targeting properties of Re for example toward mitochondria. Through the example of the diseleno-Re complex, we showed that the main target could be the oxidative status, with a down-stream regulation of signaling pathways, and further on selective cell death of cancer cells versus normal cells.

Rhenium‐Based Complexes and in Vivo Testing: A Brief History

“…The in vitro antiproliferative effects of rhenium‐based complexes have been extensively detailed in previous reviews [6–8] . This also includes the photophysical and photobiological properties and their applications in photodynamic therapy (PDT) and photoactivated chemotherapy (PACT).…”

Rhenium N-heterocyclic Carbene Complexes Block Growth of Aggressive Cancers by Inhibiting FGFR- and SRC-Mediated Signalling

“…Attempts to substitute platinum with other metals has not produced tangible results in a clinical setting. Among all metal-based drugs, those containing rhenium have recently attracted major interest: several rhenium-based compounds have been tested for their anticancer activity in vitro and in vivo with promising results (24,(46)(47)(48)(49). However, the lack of a known mechanism of action and molecular target represents a major obstacle in advancing these therapeutics to the clinical trial stage.…”

Highly Potent Rhenium(I) Tricarbonyl Complexes with Dual Anticancer and Anti-Angiogenic Activity Against Colorectal Carcinoma

“…25,[30][31][32][33] The former type of complexes act as photodynamic therapy photosensitizers, the latter, of general formula fac-[Re(CO)3(α-diimine)PR3] + (PR3 = phosphine type-ligands) have been recently described by different authors. [34][35][36][37][38][39] Relatively recent and comprehensive reviews by Gasser et al, 11 Policar et al 40 , Lo et al, 41 Collery et al, 42 Kühn et al 43 and Wilson et al 44 have discussed the subject in detail, and it is apparent from these that the cytotoxicity of Re(I) tricarbonyl complexes is generally found to increase with lipophilicity, [45][46][47][48][49][50] (most probably due to an improved cellular uptake) although exceptions do exist. 51 Within the context above, we therefore decided to explore the antiproliferative efficacy of a series lipophilicity against different cell lines, but with a focus on cells derived from CRC.…”