Iron(III) and nickel(II) complexes of tetradentate thiosemicarbazones: Synthesis, structure, cytotoxicity, and lipophilicity

Suleymanoglu M., Kaya B., Erdem-Kuruca S., Ulkuseven B.

JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY, cilt.33, sa.10, 2019 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 33 Sayı: 10
  • Basım Tarihi: 2019
  • Doi Numarası: 10.1002/jbt.22383
  • Dergi Adı: JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Anahtar Kelimeler: cytotoxicity, iron(III), lipophilicity, nickel(II), thiosemicarbazone, RIBONUCLEOTIDE REDUCTASE INHIBITOR, SPECTROSCOPIC PROPERTIES, PHASE-I, DI-2-PYRIDYLKETONE, PERMEABILITY, COMBINATION, CYTARABINE, CHEMISTRY, CHELATORS, LEUKEMIA
  • İstanbul Üniversitesi Adresli: Evet

Özet

Eighteen of the iron(III) and nickel(II) complexes with tetradentate thiosemicarbazidato ligands were synthesized and described, by analytical and spectroscopic methods. Two complexes as an example to the iron and nickel centered ones were crystallographically analyzed to confirm the molecular structures. Cytotoxic effects of the complexes on K562 chronic myeloid leukemia cells were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. For comparison, human umbilical vein endothelial cells (HUVECs) was used as a noncancerous cell line. While four of the iron(III) complexes exhibited the antileukemic effect with 50% inhibition of cell growth (IC50) values in the 3.4 to 6.9 mu g/mL range on K562 cell line, the nickel(II) complexes showed no significant effect on both cell lines. The complexes Fe4, Fe5, and Fe6, bearing 4-methoxy substituent exhibited relatively high antiproliferative activity on both cell lines. Complex Fe3 with 3-methoxy and S-allyl groups exhibited a selectivity between K562 and HUVEC cells by IC50 values of 6.9 and >10 mu g/mL, respectively. Lipophilicity, a key parameter for bioavailability and oral administration, was found in the range of -0.3 and +1.3 that desired for drug active ingredients. The results were discussed in the context of a structure-activity relationship.