Ruthenium(II)-diphosphine compounds showed potent cytotoxicity with IC50 as low as 0.48 μM on A549 lung cancer cells by inducing mitochondrial dysfunction.
Ruthenium(II)‐diphosphine compounds demonstrate promising anticancer potential by inducing mitochondrial dysfunction and altering oxygen consumption in A549 cancer cells.
In this work, we studied six Ruthenium (II) ‐diphosphine compounds containing different mercapto ligands (N−S), with general formula Ru (N−S) (dppm) ₂Cl (dppm=1, 1‐bis (diphenylphosphino) methane). These compounds were characterized by several techniques (NMR ^1H, ^31P (^1H), and ^13C, HRMS, IR, UV‐Vis and XRD) and their purity confirmed by elemental analysis. DLS experiments revealed low diameters and polydispersity indexes, and positive log P values in n‐octanol/PBS indicated their preference for the organic phase. In general, these compounds are stable in different media over 48 h. Cytotoxicity experiments revealed promising IC₅₀ values on A549 breast cancer cells, 0. 48 μM and 0. 80 μM for Ru (mtz) (dppm) ₂Cl (1) and Ru (mmi) (dppm) ₂Cl (2), respectively (mtz and mmi are 2‐mercapto‐2‐thiazoline and mercapto‐1‐methylimidazole in their deprotonated form, respectively). Clonogenic and migration experiments indicated their antiproliferative and anti‐migratory capacity. ICP‐MS results indicated their cellular accumulation in the nucleus, with little amounts in mitochondria. No covalent DNA binding was observed by ICP‐MS. JC‐1 and cell Mito Stress test confirmed mitochondrial dysfunction, which was verified by mitochondrial membrane potential uncoupling and drastic alterations in the oxygen consumption rate. Taken together, our results provide crucial insights regarding the anticancer potential of ruthenium (II) ‐phosphine compounds.
Palmeira-Mello et al. (2025) studied this question. Ruthenium(II)-diphosphine compounds showed potent cytotoxicity with IC50 as low as 0.48 μM on A549 lung cancer cells by inducing mitochondrial dysfunction.