Department of Medical Biology, Istanbul Faculty of Medicine, Istanbul University, Çapa, Istanbul, Turkey.
Department of Physiology, Istanbul Faculty of Medicine, Istanbul University, Çapa, Istanbul, Turkey.
J Biochem Mol Toxicol. 2020 Aug;34(8):e22512. doi: 10.1002/jbt.22512. Epub 2020 Apr 21.
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 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─H···O and C─H···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 IC 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.
通过一锅合成法合成了带有硫代缩氨基脲骨架的铁（III）和镍（II）配合物。通过元素分析、IR、 1H NMR、APCI 质量、电导率和磁矩测量对结构进行了表征。通过单晶 X 射线衍射获得了铁（III）配合物的分子和晶体结构。结果表明，金属原子采用略微扭曲的四方锥配位，硫代缩氨基脲配体的四个供体原子定义了基平面，一个氯离子占据了顶点位置。在晶格中，结构通过分子间的 O─H···O 和 C─H···O 相互作用稳定。通过 MTT 测定法研究了细胞毒性活性，通过 Western blot 研究了细胞色素 P450（CYP）酶的表达水平，通过振摇瓶法（另一种药代动力学参数）研究了亲脂性（LogP）。结果表明，IC 值随物质 LogP 值的降低而降低。细胞色素 P450 表达水平针对每种化合物和每种细胞系是特异性的。因此，新合成的硫代缩氨基脲化合物的药代动力学性质对于口服给药至关重要，并为未来的体内研究提供了线索。
