Cytotoxicity of Ruthenium(II) Arene Complexes Containing Functionalized Ferrocenyl β-Diketonate Ligands

Abstract

The synthesis and characterization of 24 ruthenium(II) arene complexes of the type [(p-cym)RuCl(Fc-acac)] (where p-cym = p-cymene and Fc-acac = functionalized ferrocenyl β-diketonate ligands) are reported, including single-crystal X-ray diffraction for 21 new complexes. Chemosensitivity studies have been conducted against human pancreatic carcinoma (MIA PaCa-2), human colorectal adenocarcinoma p53-wildtype (HCT116 p53 +/+) and normal human retinal epithelial cell lines (APRE-19). The most active complex, which contains a 2-furan-substituted ligand (4), is 5x more cytotoxic than the analogs 3-furan complex (5) against MIA PaCa-2. Several complexes were screened under hypoxic conditions and at shorter-time incubations, and their ability to damage DNA was determined by the comet assay. Compounds were also screened for their potential to inhibit the growth of both bacterial and fungal strains.

Half-Sandwich Iridium(III), Rhodium(III), and Ruthenium(II) Complexes Chelating Hybrid sp2-N/sp3-N Donor Ligands to Achieve Improved Anticancer Selectivity

“…Chemotherapy has been the predominant strategy for cancer clinical treatments despite the significant advances over the last 50 years in this field. Platinum metal-based anticancer agents including cisplatin, carboplatin, and oxaliplatin have proved to be a great success in chemotherapy of different tumors. , However, these drugs suffer from lack of cancer cell selectivity, serious side effects, and drug resistance. − As such, the design and development of new metallic anticancer drugs with high anticancer activity and selectivity to reduce side effects and new mechanism of actions (MoAs) to overcome drug resistance have been the focus of many researchers in both research and commercial organizations. − Anticancer complexes of a variety of platinum group metals (Ir, Rh, Ru, and Os) have been widely developed. Two notable ruthenium complexes KP1019 and NAMI-A have displayed the most satisfying results in preclinical and clinical treatment. , In recent years, the organometallic half-sandwich platinum group metal complexes have featured as a versatile platform for the development of anticancer metallodrugs due to their structure diversity and different MoAs with platinum drugs. − …”

Biomolecular Interactions and Anticancer Mechanisms of Ru(II)-Arene Complexes of Cinnamaldehyde-Derived Thiosemicarbazone Ligands: Analysis Combining In Silico and In Vitro Approaches

“… Ru complexes are fairly less toxic than the platins, as Ru mimics Fe in the body and could undergo similar transformations as Fe in crucial bodily processes. Besides these striking differences, Ru complexes (particularly, Ru-arene piano-stool complexes) show some properties which are hallmarks of platins, such as binding ability with nucleic acids, and serum proteins . The labile axial ligands of Ru(II) complexes engage with disease targets via ligand-exchange reactions, exhibiting exchange rates akin to those of Pt(II) complexes, and operating within cellular time scales. , Furthermore, Ru-arene complexes have been reported to inhibit trans-plasma membrane electron transport activity, lactate production, topoisomerase and cause DNA fragmentation, cell apoptosis via various pathways .…”

Potent Half-Sandwich 16-/18-Electron Iridium(III) and Ruthenium(II) Anticancer Complexes with Readily Available Amine–Imine Ligands

“…Chemotherapy has been the primary approach to cancer treatment, despite significant advancements over the past 50 years. Platinum-based drugs, which mainly comprised cisplatin, carboplatin, and oxaliplatin, have been well-studied in treating various tumors. , However, these anticancer drugs lack selectivity, have many serious side effects, and can lead to drug resistance. − As a result, many research efforts have focused on developing alternative anticancer complexes with high selectivity and novel mechanisms of action (MoAs) to reduce side effects and overcome drug resistance. − Various complexes of platinum group metals, including iridium, rhodium, ruthenium, and osmium, have been developed for this purpose. In particular, azole-based ruthenium complexes, NAMI-A and KP1019, have entered clinical trials. , …”