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

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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.

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Carvalho, D. E. L., Oliveira, K. M., Bomfim, L. M., Soares, M. B. P., Bezerra, D. P., Batista, A. A., & Correa, R. S. (2020). Nucleobase Derivatives as Building Blocks to Form Ru(II)-Based Complexes with High Cytotoxicity. ACS Omega, 5(1), 122–130. https://doi.org/10.1021/acsomega.9b01921

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