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

Vajs, Jure; Steiner, Ivana; Brozović, Anamaria; Pevec, Andrej; Ambriović Ristov, Andreja; Matković, Marija; Piantanida, Ivo; Urankar, Damijana; Osmak, Maja; Košmrlj, Janez (2015) The 1,3-diaryltriazenido(p-cymene)ruthenium(II) complexes with a high in vitro anticancer activity. Journal of Inorganic Biochemistry, 153 . pp. 42-48. ISSN 0162-0134

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Abstract

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 triazenido-ruthenium complexes were highly cytotoxic against human cervical carcinoma HeLa cells with IC50 below 6μM, 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±0.006μM. 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.

Item Type:	Article
Additional Information:	We acknowledge a financial support from the Ministry of Science, Education and Sport of the Republic of Croatia (Projects 098-0982913-2748, 098-0982913-2850 and 098-0982914-2918) and the Ministry of Education, Science and Sport, Republic of Slovenia, the Slovenian Research Agency (Grant P1-0230; Young Researcher Grant to J.V., and Grant P1-0175). This work was also partially supported through the infrastructure of the EN-FIST Centre of Excellence, Ljubljana, Slovenia. A financial support from the Joint Projects BI-HR/12-13-028 and BI-HR/14-15-007 is also acknowledged. We thank Dr. Romana Cerc Korosec for the TG/DSC measurements and Mrs. Ljiljana Babic for the technical assistance.
Uncontrolled Keywords:	Anticancer activity; Ruthenium complexes; Triazene; Triazenido
Subjects:	INTERDISCIPLINARY AREAS OF KNOWLEDGE
Divisions:	Division of Molecular Biology
Projects:	Project title Project leader Project code Project type Povećanje transdukcije adenovirusnih vektora i otpornost stanica na citostatike- Andreja Ambriović Ristov 098-0982913-2850 MZOS Stanični odgovor na citotoksične spojeve i razvoj otpornosti- Maja Osmak 098-0982913-2748 MZOS Dizajn, sinteza i ispitivanje interakcija malih molekula s DNA, RNA i proteinima- Ivo Piantanida 098-0982914-2918 MZOS
Depositing User:	Anamaria Brozović
Date Deposited:	16 Nov 2018 13:21
URI:	http://fulir.irb.hr/id/eprint/4306
DOI:	10.1016/j.jinorgbio.2015.09.005

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