Synthesis, structural, cytotoxic and pharmacokinetic evaluation of some thiosemicarbazone derivatives

Suleymanoglu M., KURUCA D. S., BAL DEMİRCİ T., Özdemir N., ÜLKÜSEVEN B., Yaylim I.

JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY, cilt.34, sa.8, 2020 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 34 Sayı: 8
  • Basım Tarihi: 2020
  • Doi Numarası: 10.1002/jbt.22512
  • Dergi Adı: JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Agricultural & Environmental Science Database, Applied Science & Technology Source, BIOSIS, Biotechnology Research Abstracts, Chemical Abstracts Core, EMBASE, Environment Index, Food Science & Technology Abstracts, MEDLINE
  • Anahtar Kelimeler: Cytochrome P450 (CYP) enzymes, cytotoxicity, lipophilicity, pharmacokinetics, thiosemicarbazones, CYTOCHROME-P450 ENZYMES, NICKEL(II) COMPLEXES, IRON(III), COPPER(II), CRYSTAL, LIGANDS, FE(III), AGENTS, 3-AP
  • Ondokuz Mayıs Üniversitesi Adresli: Evet

Özet

Iron(III) and nickel(II) complexes bearing a thiosemicarbazone framework were synthesized by a one-pot synthesis method. The structures were characterized by elemental analysis, IR, H-1 NMR, APCI Mass, conductivity, magnetic moment measurements. Molecular and crystal structures of the iron(III) complex were obtained from single-crystal X-ray diffraction. The findings showed that the metal atom adopts a slightly distorted square-pyramidal coordination, with the four donor atoms of the thiosemicarbazone ligand defining the basal plane and a chloride atom occupying the apical position. In the crystal lattice, the structure is stabilized by intermolecular O & x2500;H center dot center dot center dot O and C & x2500;H center dot center dot center dot O interactions. The cytotoxic activity was studied by MTT assay, the expression levels of cytochrome P450 (CYP) enzymes by Western blot, and the lipophilicity (LogP) by using the shake-flask method, another pharmacokinetic parameter. The findings showed that the IC50 values decreased with the decrease of the LogP values of the substances. Cytochrome P450 expression levels were found specific for each compound and each cell line. As a result, the pharmacokinetic properties of the newly synthesized thiosemicarbazone compounds are crucial for oral administration and provide us with clues for prospective in vivo studies.