Synthesis and in vitro Anticancer Activity of Ruthenium–Cymene Complexes with Cyclohexyl‐Functionalized Ethylenediamine‐N,N′‐diacetate‐Type Ligands

• DOI: 10.1002/cmdc.201100232
• Publication Date: 2011-07-29T15:23:52Z
• Authors: Aleksandar Savić; Marija Dulović; Jelena M. Poljarević; Sonja Misirlić‐De...; Maja Jovanović; Andrija Bogdanović; Vladimir Trajković; Tibor J. Sabo; Sanja Grgurić‐Šipka; Ivanka Marković
• Keywords: mitochondrial depolarization; apoptosis; leukemia; Antineoplastic Agents; Apoptosis; Stereoisomerism; Ethylenediamines; Ligands; 01 natural sciences; Ruthenium; 0104 chemical sciences; 3. Good health; Structure-Activity Relationship; Coordination Complexes; Cell Line, Tumor; Neoplasms; cancer; Humans; ruthenium

AbstractHerein we describe the synthesis, characterization, and anticancer activity of novel p‐cymeneruthenium(II) complexes containing methyl, ethyl, n‐propyl, and n‐butyl esters of (S,S)‐ethylenediamine‐N,N′‐di‐2‐(3‐cyclohexyl)propanoic acid. The results of IR, UV/Vis, ESIMS, 1H, and 13C NMR characterization reveal that ligand coordination occurs through nitrogen donor atoms of the ester ligands, with the organoruthenium moiety being kept in complex. These ruthenium(II) complexes are cytotoxic toward various cancer cell lines including leukemic HL‐60, K562, and REH cells (IC50: 1.0–20.2 μM), with the n‐butyl ester complex being the most effective. It causes apoptotic cell death associated with mitochondrial depolarization, caspase activation, phosphatidylserine exposure, and DNA fragmentation. Importantly, the n‐butyl ester complex is more effective against leukemic patients′ blood mononuclear cells relative to those from healthy control subjects, thus indicating a fairly selective antileukemic action of RuII‐based compounds.