Effect of , Coordination and Ru Halide Bond in Enhancing Selective Toxicity of a Tyramine-Based Ru (-Cymene) Complex.

Ruthenium compounds are promising anticancer candidates owing to their lower side-effects and encouraging activities against resistant tumors. Half-sandwich piano-stool type Ru compounds of general formula [(L)Ru(η-arene)(X)] (L = chelating bidentate ligand, X = halide) have exhibited significant therapeutic potential against cisplatin-resistant tumor cell lines. In Ru (-cymene) based complexes, the change of the halide leaving group has led to several interesting features, viz., hydrolytic stability, resistance toward thiols, and alteration in pathways of action. Tyramine is a naturally occurring monoamine which acts as a catecholamine precursor in humans. We synthesized a family of , and , coordinated Ru (-cymene) complexes, [(L)Ru(η-arene)(X)] (-), with tyramine and varied the halide (X = Cl, I) to investigate the difference in reactivity. Our studies showed that complex bearing , coordination with an iodido leaving group shows selective cytotoxicity against the pancreatic cancer cell line MIA PaCa-2 (IC ca. 5 μM) but is less toxic to triple-negative breast cancer (MDA-MB-231), hepatocellular carcinoma (Hep G2), and the normal human foreskin fibroblasts (HFF-1). Complex displays stability toward hydrolysis and does not bind with glutathione, as confirmed by H NMR and ESI-HRMS experiments. The inert nature of leads to enhancement of cytotoxicity (IC = 5.3 ± 1 μM) upon increasing the cellular treatment time from 48 to 72 h.