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

Abstract

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-[RuCl2(PPh3)2(bipy)] as a precursor. The obtained compounds with a general formula trans-[Ru­(2TU)­(PPh3)2(bipy)]­PF6 (1) and trans-[Ru­(6m2TU)­(PPh3)2(bipy)]­PF6 (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 G1/G0, G2/M, and S phases.

Ru(II)-based complexes containing 2-thiouracil derivatives suppress liver cancer stem cells by targeting NF-κB and Akt/mTOR signaling

“…Ru(II) complexes 1 and 2 were synthesized using the complex precursor cis, trans- [RuCl 2 (PPh 3 ) 2 (bipy)] and the ligands 2TU or 6m2TU, as previously described [ 15 ]. Both complexes were characterized by analytical techniques.…”

“…Recently, we synthesized two cytotoxic Ru(II)based complexes containing 2-thiouracil derivatives with the chemical formulas trans-[Ru(2TU)(PPh 3 ) 2 (bipy)]PF 6 (1) and trans-[Ru(6m2TU)(PPh 3 ) 2 (bipy)]PF 6 (2), where 2TU = 2-thiouracil and 6m2TU = 6-methyl-2-thiouracil (Fig. 1A) [15]. In the present work, we demonstrated the ability of complexes 1 and 2 to effectively suppress liver CSCs through targeted inhibition of the NF-κB and Akt/mTOR signaling pathways.…”