A mononuclear copper(II) complex containing benzimidazole and pyridyl ligands: Synthesis, characterization, and antiproliferative activity against human cancer cells

KAÇAR S., Unver H., ŞAHİNTÜRK V.

ARABIAN JOURNAL OF CHEMISTRY, cilt.13, sa.2, ss.4310-4323, 2020 (SCI-Expanded) identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 13 Sayı: 2
  • Basım Tarihi: 2020
  • Doi Numarası: 10.1016/j.arabjc.2019.08.002
  • Dergi Adı: ARABIAN JOURNAL OF CHEMISTRY
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Compendex, INSPEC, Directory of Open Access Journals
  • Sayfa Sayıları: ss.4310-4323
  • Anahtar Kelimeler: Copper(II) complex, MTT cytotoxicity, Immunocytochemistry, H-E, DU145 human prostate cancer cells, SPC mesothelioma cells, NIH/3T3 fibroblast cells, Apoptosis, PARAPTOTIC DEATH, IN-VIVO, STRESS, DERIVATIVES, APOPTOSIS, INHIBITION, DNA
  • Eskişehir Osmangazi Üniversitesi Adresli: Evet

Özet

Metal complexes are recently being hybridized with different moieties to discover new drugs due to their advantageous attributes. Among the metals, copper is a good one to synthesize a metal complex due to its being endogenous, redox and DNA cleavage potential, reported anticancer efficacies and selective permeability for cancer cells. In this study, first we synthesized a new copper (II) complex and determined its toxic doses on NIH/3T3 normal fibroblast cells, SPC212 mesothelioma and DU145 prostate cancer cells. Then, we ascertained anti-proliferative, apoptotic, morphological, oxidative and endoplasmic reticulum (ER) stress inducing effects of these newly synthesized compounds on DU145 prostate cancer cells. A novel Copper(II)/1-(4-(trifluoro methyl)benzyl)-1H-benzimidazole/2,2'-bipyridyl complex was synthesized and mainly characterized by single crystal X-ray diffraction analysis. Anti-proliferative effect of copper(II) complex was gauged by MTT. Oxidative and ER stress were evaluated by ELISA and Western blot. The morphological effect was examined by microscope analysis. Besides, immunocytochemistry of Bax, a pro-apoptotic protein and PCNA, a proliferation marker protein was performed. As a result, the inhibitory effect of newly synthesized substance was superior to the chemicals from which it was synthesized. Its IC(50)s against DU145 were 37.0, 21.1 and 10.0 mu M for 24, 48 and 72 h-treatments, respectively. Oxidative and ER stress increased after treatment. In microscopy, we observed apoptotic hallmarks like nuclear condensation, cellular shrinkage and membrane