Ruthenium based complexes have recently gained interest for their potential role in photoactivated chemotherapy. In the present study, we investigated the anticancer activity of two synthesized ruthenium complexes: Ru(bipy)2(dppH)Cl2 [ruthenium(II) bis(2,2’-bipyridine)(2,9-diphenyl-1,10-phenanthroline) chloride] (complex 1) and Ru(bipy)2(phen)Cl2 [ruthenium(II) bis(2,2’-bipyridine)(1,10-phenanthroline) chloride (complex 2). The phenyl groups at the 2,9-positions of the phenanthroline group increased the steric strain of complex 1 and distorted its geometry. Upon visible light excitation, complex 1 undergoes dissociation of the bpy ligand and releases a Ru(bipy)(dppH)(H2O)2+ complex. Complex 2 was included as an unstrained and photostable control. Complexes 1 and 2 cytotoxicity were investigated using WST-1 cell survival assay on five different cell lines: triple negative human breast adenocarcinoma MDA-MB-231, murine melanoma B16-F10, human alveolar adenocarcinoma A549, human colorectal adenocarcinoma HT29 and human colon adenocarcinoma Caco-2. Complex 1 exhibited modest activity in the dark with an IC50 of 55.1 µM in B16-F10 to &gt;100 µM in remaining cell lines. Upon photoactivation, cytotoxicity increased drastically in all tested cell lines (IC50 ranged from 0.82 µM in B16-F10 cells to a maximum of 2.55 µM in A549 cells) and it was many fold that of cisplatin. The phototoxicity index PI = [IC50 dark] / [IC50 light] ranged from 39.2-fold in A549 to over 100-fold in MDA-MB-231. The dissociating ligand bpy was biologically inert in almost all cell lines, confirming that phototoxicity is mediated by the ruthenium aqua which is released upon irradiation. The IC50 of complex 2 in both dark and light conditions was &gt;100 µM, hence confirming the role of the coordinating ligand in distorting the structure of Ru(II) polypyridyl complexes and mediating phototoxicity. Flow cytometry analysis revealed that complex 1 exert its cytotoxic effect via promoting late apoptosis. In conclusion, the synthesized complex 1 induce apoptosis upon photoejection of the inert bpy ligand and release of a highly toxic Ru(II) aqua complex.

Photocytotoxicity assessment of a ruthenium(II) polypyridyl complex bearing 2,9-diphenyl-1,10-phenanthroline ligand

255th National Meeting (2018)

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