Synthesis and characterization of thiosemicarbazone-functionalized organoruthenium (II)-arene complexes: Investigation of antitumor characteristics in colorectal cancer cell lines

In the current study, organoruthenium(II)-arene complexes (I-IV) have been prepared by the reaction of [{(?6-p-cym)RuCl}2(µ-Cl)2] with new thiosemicarbazones (TSC1–4).The isolate was analyzed using elemental analysis, FT-IR, 1H and 13C NMR spectroscopy and single-crystal XRD. Subsequently, the complexes and TSC ligands were assessed for anticancer properties in vitro against three different colorectal cancer stage's cell lines (Caco-2, DLD-1, and SW620) and a noncancerous cell line (CCD18Co). The complexes (I-IV) showed higher cytotoxicity with low IC50 values as 0.1–0.33 µM in colorectal cell lines except for SW620 (47.4–84.20 µM) than in a noncancerous cell. Complex I was 2.8 and 24.5-fold more active against Caco-2 and DLD-1 than CCD18Co, respectively. The complexes (I-IV) accumulated at a high concentration in the cell nuclei and caused cell cycle arrest by affecting the G0/G1 and/or G2/M phase and showed high binding affinity with CT-DNA (Kb = 104 M- 1). The expression of Caspase-3 and Caspase-9 apoptosis-related protein levels was slightly upregulated and Atg5 autophagy-related protein level was clearly downregulated according to control and 5-FU-treated cells after complex I and II treatment. Furthermore, it was observed that cytotoxicity of the complexes is decreased while cancer progresses. Altogether, this study indicates that all organoruthenium (II)-arene complexes (particularly complex I) can be a promising alternative to platinum counterparts in cancer treatment. © 2019Dokuz Eylül Üniversitesi Türkiye Bilimsel ve Teknolojik Araştirma KurumuThis study was financed by project number 215Z663 TUBITAK (The Scientific and Technological Research Council of Turkey ). The authors acknowledge Dokuz Eylül University for the use of the Oxford Rigaku Xcalibur Eos Diffractometer (purchased under University Research Grant No: 2010.KB.FEN.13) and Izmir Biomedicine and Genome Center. We also gratefully thank Zehra Tavsan for her help in vitro part. -