Ruthenium(II) Complex with 1-Hydroxy-9,10-Anthraquinone Inhibits Cell Cycle Progression at G0/G1 and Induces Apoptosis in Melanoma Cells

钌(II)与1-羟基-9,10-蒽醌的配合物抑制G0/G1期细胞周期进程并诱导黑色素瘤细胞凋亡

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作者:Júlia S M Dias, Guilherme A Ferreira-Silva, Rommel B Viana, João H de Araujo Neto, Javier Ellena, Rodrigo S Corrêa, Marília I F Barbosa, Marisa Ionta, Antônio C Doriguetto

Background

Melanoma is the most aggressive and lethal skin cancer that affects thousands of people worldwide. Ruthenium complexes have shown promising

Conclusions

The cytotoxicity profiles of the compounds were evaluated in human melanoma cell lines (SK-MEL-147, CHL-1, and WM1366), revealing greater cytotoxic activity for (1) on the CHL-1 cell line with an IC50 of 14.50 ± 1.09 µM. Subsequent studies showed that (1) inhibits the proliferation of CHL-1 cells and induces apoptosis, associated at least in part with the pro-oxidant effect and cell cycle arrest at the G1/S transition.

Methods

The complexes were characterized by infrared (IR), UV-vis, 1H, 13C{1H}, and 31P{1H} NMR spectroscopies, molar conductivity, cyclic voltammetry, and elemental analysis. Furthermore, density functional theory (DFT) calculations were performed.

Results

Compound (2) was determined by single-crystal X-ray diffraction, which confirms the bidentate coordination mode of HQ through the carbonyl and phenolate oxygens. Additionally, DNA-binding experiments yielded constants of 105 M-1 (Kb = 6.93 × 105 for (1) and 1.60 × 105 for (2)) and demonstrate that both complexes can interact with DNA through intercalation, electrostatic attraction, or hydrogen bonding. Conclusions: The cytotoxicity profiles of the compounds were evaluated in human melanoma cell lines (SK-MEL-147, CHL-1, and WM1366), revealing greater cytotoxic activity for (1) on the CHL-1 cell line with an IC50 of 14.50 ± 1.09 µM. Subsequent studies showed that (1) inhibits the proliferation of CHL-1 cells and induces apoptosis, associated at least in part with the pro-oxidant effect and cell cycle arrest at the G1/S transition.

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