4.7 Article

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

Journal

DALTON TRANSACTIONS
Volume 51, Issue 22, Pages 8804-8820

Publisher

ROYAL SOC CHEMISTRY
DOI: 10.1039/d1dt04294g

Keywords

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Funding

  1. National Science Center, Poland [2014/15/B/NZ4/00751]

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Three ruthenium(i) complexes containing purine analogs were synthesized and characterized. They showed potential as photo-activated CO-releasing molecules and CO-based therapies. The impact of UV-induced modification on their anticancer properties was investigated.
Three sawhorse-type ruthenium(i) complexes containing purine analogs such as triazolopyrimidines of the general formula (Ru-2(CO)(4)(mu-OOCCH3)(2) (L)(2)), where L is 1,2,4-triazolo[1,5]-alpyrimidine (tp for 1), 5,7-ditertbutyl-1,2,4-triazolol[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 (H-1, C-13, N-15), 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)(mu-OOCCH3)(7)(tp)(2)] (1) (log P = -112) 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 (IC50 = 154.7 +/- 6.5 mu M) in comparison with HeLa cancer cells (IC50 = 66.7 1 3.4 mu M). The photo-induced stimulation of (1) and (2) increases ROS generation, and their anticancer activity may be a partially ROS-dependent phenomenon.

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