Sawhorse-type ruthenium complexes with triazolopyrimidine ligands - what do they represent in terms of cytotoxic and CORM compounds?

Three sawhorse-type ruthenium(I) complexes containing purine analogs such as triazolopyrimidines of the general formula [Ru 2 (CO) 4 (μ-OOCCH 3 ) 2 (L) 2 ], where L is 1,2,4-triazolo[1,5- a ]pyrimidine (tp for 1), 5,7-ditertbutyl-1,2,4-triazolo[1,5- a ]pyrimidine (dbtp for 2) and 5,7-diphenyl-1,2,4-triazolo[1,5- a ]pyrimidine (dptp for 3), have been synthesized and characterized by elemental analysis, infrared analysis, multinuclear magnetic resonance spectroscopic techniques ( 1 H, 13 C, 15 N), and single-crystal X-ray diffraction (for 1 and 2). By assay with myoglobin, the photo-activated CO-releasing molecule (PhotoCORM) character of (1-3) has been confirmed, thus indicating the possibility of use in CO-based therapies. The importance of UV-induced modification has been investigated in the context of anticancer properties. Complexes (1) and (2) have been thoroughly screened for their in vitro cytotoxicity against various cancer cell lines: MCF-7 (breast cancer), HeLa (cervical cancer) and C32 (melanoma), as well as L929 normal fibroblasts in the dark and presence of UV-A light (365 nm). The results were compared with those for cisplatin and two reference ruthenium complexes, namely NAMI-A and KP1019. The most hydrophilic [Ru 2 (CO) 4 (μ-OOCCH 3 ) 2 (tp) 2 ] (1) (log  P = -1.12) was found to be more cytotoxic than (2), despite the lower cellular uptake measured by ICP-MS toward HeLa cells. Importantly, photo-induced stimulation of cells with (1) resulted in a lower decrease in the viability of L929 normal cells (IC 50 = 154.7 ± 6.5 μM) in comparison with HeLa cancer cells (IC 50 = 66.7 ± 3.4 μM). The photo-induced stimulation of (1) and (2) increases ROS generation, and their anticancer activity may be a partially ROS-dependent phenomenon.