Naslov
The 1, 3-diaryltriazenido(p-cymene)ruthenium(II) complexes with a high in vitro anticancer activity

Autori
Vajs, Jure ; Steiner, Ivana ; Brozović, Anamaria ; Pevec, Andrej ; Ambriović-Ristov, Andreja ; Matković, Marija ; Piantanida, Ivo ; Urankar, Damijana ; Osmak, Maja ; Janez Košmrlj

Izvornik
Journal of inorganic biochemistry (0162-0134) 153 (2015); 42-48

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
Ruthenium complexes; Triazene; Triazenido; Anticancer activity

Sažetak
1, 3-Diaryltriazenes (1) were let to react with [RuCl2(p-cymene)]2 in the presence of trimethylamine to give neutral 1, 3-diaryltriazenido(p-cymene)ruthenium(II) complexes, [RuCl(p-cymene)(ArNNNAr)] (2). The molecular composition of the products 2 was confirmed by NMR spectroscopy and mass spectrometry. The structures of the selected complexes were confirmed by a single crystal X-ray analysis. All ruthenium-triazenide complexes were highly cytotoxic against human cervical carcinoma HeLa cells with IC50 below 6 µM, as determined by a spectrophotometric MTT (3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl-tetrazolium bromide) method. The most active was [RuCl(p-cymene)(ArNNNAr)] (Ar = 4-Cl-3-(CF3)-C6H3) (2g) with IC50 of 0.103 ± 0.006 µM. In comparison with the data for the non-coordinated triazenes 1, the triazenido-ruthenium complexes 2 exhibited up to 560-times higher activity. Three selected complexes were highly cytotoxic also against several tumor cell lines: laryngeal carcinoma HEp-2 cells and their drug-resistant HEp-2 subline (7T), colorectal carcinoma HCT-116 cells, lung adenocarcinoma H460 cells, and mammary carcinoma MDA-MB-435 cells. The compounds 2g and [RuCl(p-cymene)(ArNNNAr)] (Ar = 4-I-C6H4) (2j) were similarly cytotoxic against parental and drug-resistant cells. Time and dose dependent accumulation of the cells in the S phase of the cell cycle was induced by the compound 2g, triggering apoptosis. Our preliminary results indicate triazenido-ruthenium complexes as promising anticancer drug candidates.

Izvorni jezik
Engleski

Znanstvena područja
Kemija, Biologija

POVEZANOST RADA