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Nucleobase Derivatives as Building Blocks to Form Ru(II)-Based Complexes with High Cytotoxicity.
ACS Omega ( IF 4.1 ) Pub Date : 2020-01-03 , DOI: 10.1021/acsomega.9b01921
Diogo E L Carvalho 1 , Katia M Oliveira 1 , Larissa M Bomfim 2 , Milena B P Soares 2 , Daniel P Bezerra 2 , Alzir A Batista 3 , Rodrigo S Correa 1
Affiliation  

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.

中文翻译:

核碱基衍生物作为形成具有高细胞毒性的Ru(II)基复合物的基础。

使用顺式,反式-[RuCl2(PPh3)2(bipy) )]作为前体。通过分析表征了具有通式反式-[Ru(2TU)(PPh3)2(bipy)] PF6(1)和反式-[Ru(6m2TU)(PPh3)2(bipy)] PF6(2)的化合物NMR,UV-vis和IR光谱,元素分析,质谱和单晶X射线衍射等技术。此外,使用分光光度滴定法对复合物与DNA的相互作用进行了研究,结果表明复合物与该生物分子的相互作用较弱。针对HL-60,K-562,HepG2和B16-F10癌细胞以及非癌细胞(PBMC)对化合物进行了评估。
更新日期:2020-01-14
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