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

Subasi E., Atalay E., Erdogan D., Sen B., Pakyapan B., Kayali H. A.

MATERIALS SCIENCE & ENGINEERING C-MATERIALS FOR BIOLOGICAL APPLICATIONS, cilt.106, 2020 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 106
  • Basım Tarihi: 2020
  • Doi Numarası: 10.1016/j.msec.2019.110152
  • Dergi Adı: MATERIALS SCIENCE & ENGINEERING C-MATERIALS FOR BIOLOGICAL APPLICATIONS
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Aerospace Database, Agricultural & Environmental Science Database, Biotechnology Research Abstracts, Communication Abstracts, Compendex, EMBASE, INSPEC, MEDLINE, Metadex, Civil Engineering Abstracts
  • Anahtar Kelimeler: Organoruthenium (II)-arene complexes, Thiosemicarbazone, Antitumor activity, Colorectal cancer cell lines, Crystal structure, CRYSTAL-STRUCTURE, DNA-BINDING, RUTHENIUM, MEDICINE
  • Sivas Cumhuriyet Üniversitesi Adresli: Evet

Özet

In the current study, organoruthenium(II)-arene complexes (I-IV) have been prepared by the reaction of ({(eta(6)-pcym)RuCl}(2)(mu-Cl)(2)] with new thiosemicarbazones (TSC1-4).The isolate was analyzed using elemental analysis, FT-IR, H-1 and C-13 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 mu M in colorectal cell lines except for SW620 (47.4-84.20 mu M) 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 = 10(4) 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.