Phosphine/diimine ruthenium complexes with Cl-, CO, NO+, NO2-, NO3- and pyridine ligands: Pro-apoptotic activity on triple-negative breast cancer cells and DNA/HSA interactions

A series of five new ruthenium phosphine/diimine complexes were prepared and characterized by IR, UV-Vis, H-1, P-31[H-1] and C-13[H-1] NMR spectroscopies, elemental analyses and cyclic voltammetry. Four of the complexes have the general formula ct-{[}RuCl(L)(dppb)(4,4'-Mebipy)](PF6)(n) (dppb = 1,4-bis (diphenylphosphino)butane, 4,4'-Mebipy = 4,4'-dimethyl-2,2-bipyridine and L = CO, NO+, NO2- or pyridine), and one has the formula {[}Ru(NO3)(dppb)(4,4'-Mebipy)]PF6, where NO3- is a bidentate ligand. In addition, the crystal structure of the complex ct-{[}RuCl(CO)(dppb)(4,4'-Mebipy)]PF6 was elucidated by single-crystal X-ray diffraction analysis, which supported the geometry of the compounds suggested by the P-31 NMR experiments. The cytotoxic activity of the synthesized compounds was evaluated against five cancer cell lines: HepG2 (liver), HT144 (melanoma), A549 (lung), MDA-MB-231 (breast) and HCT-9 (colon). Human serum albumin (HSA) and DNA binding experiments were also conducted. The HSA binding constants and thermodynamic parameters suggested spontaneous interactions of the complexes with this protein through van der Waals forces and hydrogen bonding. A spectroscopic titration study indicated that the compounds interacted with ct-DNA, exhibiting binding constants, K-b, on the order of 1.0 x 10(4) M-1. Additionally, the ruthenium complex containing pyridine displayed cytotoxic activity against HT144, A549, and MDA-MB-231. In addition, it demonstrated pro-apoptotic activity on MDA-MB-231 cells as well as the ability to reduce colony formation. These findings are very promising and have motivated further studies for identifying the molecular target underlying the antitumor activity of the ruthenium(II)/pyridine complex against triple-negative breast cancer. (C) 2018 Elsevier Ltd. All rights reserved. (AU)