Nucleobase Derivatives as Building Blocks to Form Ru(II)-Based Complexes with High Cytotoxicity

Two new Ru(II)-based complexes containing 2-thiouracil derivatives, known as 2-thiouracil (2TU) and 6-methyl-2-thiouracil (6m2TU), were synthesized using cis,trans- [RuCl 2 (PPh 3 ) 2 (bipy)] as a precursor. The obtained compounds with a general formula trans- [Ru(2TU)(PPh 3 ) 2 (bipy)]PF 6 ( 1 ) and trans- [Ru(6m2TU)(PPh 3 ) 2 (bipy)]PF 6 ( 2 ) were characterized by analytical techniques such as NMR, UV-vis, and IR spectroscopies, elementary analysis, mass spectrometry, and single-crystal X-ray diffraction. Moreover, the investigation of the complexes-DNA interaction were carried out using spectrophotometric titrations and showed that the complexes present a weak interaction with this biomolecule. The compounds were evaluated against HL-60, K-562, HepG2, and B16-F10 cancer cells and against noncancer cells (PBMCs). The results of the biological assay revealed that complex 2 is more promising than complex 1 . Finally, the present study suggests that complexes 1 and 2 causes cell death by apoptosis, significantly increasing the percentage of apoptotic HL-60 cells, in which the compounds altered the cell cycle, reducing the cells in G 1 /G 0 , G 2 /M, and S phases.