Synthesis, structure and biological evaluation of ruthenium(III) complexes of triazolopyrimidines with anticancer properties
| Autor: | Marzena Fandzloch, Joanna Wiśniewska, Tomasz Jędrzejewski, Julia Jezierska, Liliana Dobrzańska, Iwona Łakomska |
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| Rok vydání: | 2019 |
| Předmět: |
Pyrimidine
Cell Survival Stereochemistry chemistry.chemical_element Antineoplastic Agents Apoptosis 010402 general chemistry 01 natural sciences Biochemistry Ruthenium Inorganic Chemistry HeLa Mice chemistry.chemical_compound Coordination Complexes Cell Line Tumor Octahedral molecular geometry Animals Molecule biology 010405 organic chemistry Ligand Triazoles biology.organism_classification 0104 chemical sciences Pyrimidines chemistry Cell culture DNA |
| Zdroj: | JBIC Journal of Biological Inorganic Chemistry. 25:109-124 |
| ISSN: | 1432-1327 0949-8257 |
| Popis: | Six novel ruthenium(III) complexes of general formula [RuCl3(L)3] (1,3,5) and [RuCl3(H2O)(L)2] (2,4,6), where L stands for three different triazolopyrimidine-derived ligands, are reported. The compounds have been structurally characterized (IR, EPR, SCXRD), and their magnetic moments have been determined. The single-crystal X-ray diffraction study revealed a slightly distorted octahedral geometry of the Ru(III) complexes with mer configuration in 1 and 5, and fac configuration in 3. In 2 and 4, three chloride ions are in mer configuration and the two triazolopyrimidines are oriented trans mutually with the water molecule playing the role of the sixth ligand. All complexes have been thoroughly screened for their in vitro cytotoxicity against human breast cancer cell line MCF-7, human cervical cancer cell line HeLa, and L929 murine fibroblast cells, uncovering among others that the most lipophilic complexes 5 and 6, containing the bulky ligand dptp (5,7-diphenyl-1,2,4-triazolo[1,5-a]pyrimidine), display high cytotoxic activity against MCF-7, and HeLa cells. Moreover, it was also revealed that during the interaction of the complexes 1-6 with the cancer MCF-7 cell line, reactive oxygen species are released intracellularly, which could indicate that they are involved in cell apoptosis. Furthermore, extensive studies have been carried out to reveal the mechanism by which complexes 1-6 interact with DNA, albumin, and apotransferrin. The biological studies were complemented by detailed kinetic studies of the hydrolysis of the complexes in the pH range 5-8, to determine the stability of the complexes in solution. Six novel ruthenium(III) complexes with triazolopyrimidine derivatives demonstrated the potential for use as anticancer agents by maintaining the toxic effect on MCF-7 and HeLa cells. |
| Databáze: | OpenAIRE |
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