Rationally Designed Ruthenium Complexes for Breast Cancer Therapy

Abstract

Since the discovery of the anticancer potential of ruthenium-based complexes, several species were reported as promising candidates for the treatment of breast cancer, which accounts for the greatest number of new cases in women every year worldwide. Among these ruthenium complexes, species containing bioactive ligand(s) have attracted increasing attention due to their potential multitargeting properties, leading to anticancer drug candidates with a broader range of cellular targets/modes of action. This review of the literature aims at providing an overview of the rationally designed ruthenium-based complexes that have been reported to date for which ligands were carefully selected for the treatment of hormone receptor positive breast cancers (estrogen receptor (ER+) or progesterone receptor (PR+)). In addition, this brief survey highlights some of the most successful examples of ruthenium complexes reported for the treatment of triple negative breast cancer (TNBC), a highly aggressive type of cancer, regardless of if their ligands are known to have the ability to achieve a specific biological function.

Breast Cancer Chemotherapeutic Options: A General Overview on the Preclinical Validation of a Multi-Target Ruthenium(III) Complex Lodged in Nucleolipid Nanosystems

“…Indeed, the most remarkable cytotoxic effects throughout our project have been detected in ER BC models in vitro, which roughly reflect the characteristics of luminal BCC in vivo, a widespread aggressive tumor in women [87,129,130,[138][139][140][141]145]. Interestingly, these findings are consistent with many reports showing for ruthenium complexes significant antiproliferative effects against specific subtypes of BC [124]. Thus, starting from these data, to expand knowledge for an optimal Ru-based candidate drugs development as chemotherapeutic options, we have next focused on selected in vitro models of BC-i.e., MCF-7, CG-5, MDA-MB-231, MDA-MB-468, and MDA-MB-436 cell lines-with distinct phenotypic and/or genotypic features, and different replicative and/or invasive potential.…”

“…Indeed, simultaneous action on multiple molecular targets can increase the chances of reactivating death pathways that are commonly suppressed in cancer cells by the action of oncogenes. To our knowledge, ruthenium complexes show a higher activity in several resistant cell lines, including BCC [124,175]. In this direction, the Ru-based nanosystems described herein not only can target DNA, but also enzymes and cellular proteins ( Figure 5).…”

“…In addition to the compounds ready for clinical appliance, to date numerous Ru-based derivatives, both inorganic and organic, have been investigated throughout advanced preclinical phase [ 85 , 87 , 123 ]. Indeed, several ruthenium complexes with attractive physico-chemical and biochemical properties, including superior anticancer activity, have been intensively studied as promising candidates within the frame of a prospective “ruthenotherapy” [ 124 , 125 ]. In recent years, many preclinical studies have been conducted on new Ru(II) and Ru(III) scaffolds in different phases of advancement.…”

Aberrant glycosylation patterns on cancer cells: Therapeutic opportunities for glycodendrimers/metallodendrimers oncology

“…However, the introduction of Au(III) dropped the activity in the low nM range (Caminade et al, 2018). Another interesting review based on ruthenium dendrimers used against breast cancer has also recently appeared (Golbaghi & Castonguay, 2020). In their work, a series of ruthenium(II) arene complexes bearing anastrozole as an aromatase inhibitor was prepared.…”

Microwave-assisted synthesis of ruthenium(ii) complexes containing levofloxacin-induced G2/M phase arrest by triggering DNA damage

“…15 In the last decades, various Ru(II) complexes had been designed and investigated as potential anticancer candidatures. [16][17][18][19][20][21] Quinolones, which were synthetic antibacterial agents, had been widely used in clinical practice. As one of quinoline derivatives, they could be applied as ligands on the synthesis of various metal complexes.…”