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Ruthenium tetrazene complexes bearing glucose moieties on their periphery: Synthesis,characterization, and in vitro cytotoxicity |
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| Authors: | Vojtěch Hamala Andrea Martišová Lucie Červenková Šťastná Jindřich Karban Andrej Dančo Adam Šimarek Martin Lamač Michal Horáček Tamara Kolářová Roman Hrstka Róbert Gyepes Jiří Pinkas |
| Institution: | 1. Academy of Sciences of the Czech Republic, Institute of Chemical Process Fundamentals, v.v.i., Rozvojová 135, Prague 6, 165 02 Czech Republic
Faculty of Chemical Technology, University of Chemistry and Technology Prague, Technická 5, Prague 6, 166 28 Czech Republic;2. Regional Centre for Applied and Molecular Oncology, Masaryk Memorial Cancer Institute, Žlutý kopec 7, Brno, 65653 Czech Republic;3. Academy of Sciences of the Czech Republic, Institute of Chemical Process Fundamentals, v.v.i., Rozvojová 135, Prague 6, 165 02 Czech Republic;4. Academy of Sciences of the Czech Republic, J. Heyrovský Institute of Physical Chemistry, v.v.i., Dolejškova 2155/3, Prague 8, 182 23 Czech Republic;5. Academy of Sciences of the Czech Republic, J. Heyrovský Institute of Physical Chemistry, v.v.i., Dolejškova 2155/3, Prague 8, 182 23 Czech Republic Department of Inorganic Chemistry, Charles University, Hlavova 2030, Prague 2, 128 43 Czech Republic |
| Abstract: | Ruthenium tetrazene complexes with general formula Cp*RuCl(1,4-R2N4)] (Cp* = η5-C5Me5), where R = benzyl ( 1 ), 2-fluorobenzyl ( 2 ), β-d -glucopyranosyl-unprotected ( 3a ) and acyl-protected ( 3b – d ), 2-acetamido-β-d -glucopyranosyl-unprotected ( 4a ) and acyl-protected ( 4b – d ), propyl-β-d -glucopyranoside-unprotected ( 5a ), and O-acetylated ( 5b ), were synthesized and characterized using nuclear magnetic resonance and electrospray ionization–mass spectrometry. In addition, the molecular structure of 3b was determined using X-ray crystallography. The cytotoxicity of complexes against ovarian (A2780, SK-OV-3) and breast (MDA-MB-231) cancer cell lines and noncancerous cell line HEK-293 was evaluated and compared to cisplatin activity. The carbohydrate-modified complexes bearing acyl-protecting groups exhibited higher efficacy (in low micromolar range) than unprotected ones, where the most active 4d was superior to cisplatin up to five times against all investigated cancer cell lines; however, no significant selectivity was achieved. The complex induced apoptotic cell death at low micromolar concentrations (0.5 μM for A2780 and HEK293; 2 μM for SK-OV-3 and MDA-MB-231). |
| Keywords: | anticancer activity glucose derivatives ruthenium complexes tetrazene ligands |