Iodo coordinated half-sandwich RuII-anthraimidazoldione shows stability and low cytotoxicity even under hypoxia in metastatic cancer MDA-MB-231 cells (1–2 μM), induces apoptosis without ROS, and prevents migration at IC20 dose.

The design of Ru or other metal-based anticancer agents may achieve better and faster optimization if the ligands used are also designed to have standalone functions. In this scenario, even after dissociation from the metal complex under adverse conditions, the ligand would have anti-cancer properties. In our work, we have generated a bispyrazole-containing benzimidazole ligand with potency against vascular endothelial growth factor receptor 2 (VEGFR2), which is known to have roles in vasculogenesis/angiogenesis. This ligand was used to obtain ternary Ru(ii) p-cymene complexes with the formulations [(η-p-cymene)Ru(HL)(Cl)](Cl) (1), [(η-p-cymene)Ru(HL)(Br)](Br) (2) and [(η-p-cymene)Ru(HL)(I)](I) (3). H NMR data supports that hydrolysis of the complex is governed by halide substitution, and the extent of hydrolysis followed the trend 3> 1 > 2. All the complexes have low affinity towards DNA bases (average K ∼ 10 M for CT DNA); however, all the complexes are cytotoxic in nature, with IC values less than 15 μM. The presence of excess glutathione (GSH) liberates HL from the complexes in solution. The ability of the Ru complex to impair mitochondrial function and reduce the cellular GSH pool is thought to be the reason that it retains activity in the presence of GSH despite the ability of GSH to degrade the complexes. The chloride analogue 1 shows the best in vitro cytotoxicity against a prostate cancer cell line (LNCaP), with an IC of 6.4 μM. The complexes show anti-proliferative activity by the mitochondria-mediated intrinsic apoptotic pathway. Docking studies showed that HL has high affinity towards vascular endothelial growth factor receptor 2 (VEGFR2). The complexes show anti-metastatic activity (in vitro) at almost non-toxic dosages, and the effect is sustained even 48 h after removal of the complexes from the culture media.

A slow hydrolyzing imidazole-based Ru(II)-arene complex [(L)Ru(II)(η(6)-p-cym)(Cl)](PF6) (1) with excellent stability in the extracellular chloride concentration shows better activity under hypoxia and strong resistance to glutathione (GSH) in vitro under hypoxic conditions. 1 arrests the cell cycle in sub G1 and G2/M phases and leads to apoptosis.

Photodynamic therapy (PDT) is a remarkable alternative or complementary technique to chemotherapy, radiotherapy or immunotherapy to treat certain forms of cancer. The synergistic effect of light, photosensitizer (PS) and oxygen allows for the treatment of tumours with an extremely high spatio-tumoral control, therefore minimizing the severe side effects usually observed in chemotherapy. The currently employed PDT PSs based on porphyrins have, in some cases, some limitations, which include a low absorbance in the therapeutic window, a low body clearance, photobleaching, among others. In this context, Ru(ii) polypyridyl complexes are interesting alternatives. They have low lying excited energy states and the presence of a heavy metal increases the possibility of spin-orbit coupling. Moreover, their photophysical properties are relatively easy to tune and they have very low photobleaching rates. All of these make them attractive candidates for further development as therapeutically suitable PDT PSs. In this review, after having presented this field of research, we discuss the developments made by our group in this field of research since 2017. We notably describe how we tuned the photophysical properties of our complexes from the visible region to the therapeutically suitable red region. This was accompanied by the preparation of PSs with enhanced phototoxicity and high phototoxicity index. We also discuss the use of two-photon excitation to eradicate tumours in nude mice. Furthermore, we describe our approach for the selective delivery of our complexes using targeting agents. Lastly, we report on our very recent synergistic approach to treat cancer using bimetallic Ru(ii)-Pt(iv) prodrug candidates.

Four trimethoxy-and dimethoxyphenylamine-based Schiff base (L1−L4)-bearing Ru II −p-cymene complexes (1−4) of the chemical formula [Ru II (η 6 -p-cymene)(L)(Cl)] were synthesized, isolated in pure form, and structurally characterized using single-crystal X-ray diffraction and other analytical techniques. The complexes showed excellent in vitro antiproliferative activity against *