Cytotoxicity evaluation and DNA interaction of RuII-bipy complexes containing coumarin-based ligands

被引：6
作者：
de Almeida, Patricia S. V. B. [1 ]
de Arruda, Henrique Jefferson [1 ]
Sousa, Gleyton Leonel S. [1 ]
Ribeiro, Felipe Vitorio [1 ]
de Azevedo-Franca, Jose Aleixo [2 ]
Ferreira, Larissa A. [1 ]
Guedes, Guilherme P. [3 ]
Silva, Heveline [4 ]
Kummerle, Arthur E. [1 ]
Neves, Amanda P. [1 ]
机构：
[1] Univ Fed Rural Rio De Janeiro, Inst Quim, BR 465 Km 7, BR-23890000 Seropedica, RJ, Brazil
[2] Univ Fed Juiz de Fora, Inst Ciencias Exatas, Dept Quim, Juiz De Fora, MG, Brazil
[3] Univ Fed Fluminense, Inst Quim, Niteroi, RJ, Brazil
[4] Univ Fed Minas Gerais, Inst Ciencias Exatas, Dept Quim, Belo Horizonte, MG, Brazil
来源：
DALTON TRANSACTIONS | 2021年 / 50卷 / 41期
关键词：
X-RAY STRUCTURES; RUTHENIUM(II) COMPLEXES; RU(II) COMPLEXES; N-ACYLHYDRAZONE; IN-VITRO; BINDING; ANTICANCER; PHOTOSENSITIZERS; ANTIBACTERIAL; PHOTOCLEAVAGE;
D O I：
10.1039/d1dt01567b
中图分类号：
O61 [无机化学];
学科分类号：
070301 ; 081704 ;
摘要：
Although there are various treatment options for cancer, this disease still has caused an increasing number of deaths, demanding more efficient, selective and less harmful drugs. Several classes of ruthenium compounds have been investigated as metallodrugs for cancer, mainly after the entry of imidazolH [trans-RuCl4-(DMSO-S)(imidazole)] (NAMI-A) and indazolH [trans-RuCl4-(Indazol)(2)] (KP1019) in clinical trials. In this sense, Ru-II complexes with general formula [Ru(L1-3)(bipy)(2)]PF6 (1-3) (L1 = ethyl 3-(6-methyl-2-oxo-2H-chromen-3-yl)-3-oxopropanoate, L2 = ethyl 3-(7-(diethylamino)-2-oxo-2H-chromen-3-yl)-3-oxopropanoate, L3 = ethyl 3-(8-methoxy-2-oxo-2H-chromen-3-yl)-3-oxopropanoate and bipy = bipyridine) have been synthesized. The crystal structure of 2 revealed that the Ru-II atom lies on a distorted octahedral geometry with the deprotonated ligand (L2(-)) coordinated through beta-ketoester group oxygen atoms. In vitro cytotoxic activity of the compounds was evaluated against 4T1 (murine mammary carcinoma) and B16-F10 (murine metastatic melanoma) tumor cells, and the non-tumor cell line BHK-21 (baby hamster kidney). Coordination with Ru-II resulted in expressive enhancement of cytotoxic activity. The precursors were inactive below 100 mu M and the final Ru-II complexes (1-3) showed IC50 ranging from 2.0 to 12.8 mu M; 2 being the most potent compound. DNA interaction studies revealed a greater capacity of the complexes to interact with DNA than the ligands, where, 2 exhibited the highest K-b constant of 2.2 x 10(4) M-1. Fluorescence investigation demonstrated that 1-3 are capable of quenching the fluorescence emission of the EtdBr-DNA complex up to 40%. Molecular docking showed that the interaction of 1-3 between the DNA base pairs from the coumarin portion was with scores of 67.28, 68.62 and 64.88, respectively, and 75.45 for ellipticine, suggesting an intercalative mode of binding. Our findings show that the Ru-II complexes are eligible for continuing to be investigated as potential antitumor compounds.
引用
收藏
页码：14908 / 14919
页数：12
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