Polynuclear zinc(II) complexes of thiosemicarbazone: Synthesis, X-ray structure and biological evaluation

J Inorg Biochem. 2020 Feb:203:110908. doi: 10.1016/j.jinorgbio.2019.110908. Epub 2019 Oct 31.

Abstract

Two new dimeric Zn(II) ([{ZnL1(DMSO2)}2]·DMSO (1), [{ZnL2Cl}2] (2)) and a novel tetrameric Zn(II) complex ([(Zn2L3)2(μ-OAc)23-O)2] (3)), where H2L1 = 4-(p-methoxyphenyl) thiosemicarbazone of o-hydroxynapthaldehyde, HL2 = 4-(p-methoxyphenyl)thiosemicarbazone of benzoyl pyridine and H2L3 = 4-(p-chlorophenyl)thiosemicarbazone of o-vanillin are reported. Ligands and their complexes were characterized by spectroscopic and single crystal X-ray diffraction techniques. In addition, the complexes exhibited good binding affinity towards HSA (1012 M-1), which is supported by their ability to quench the tryptophan fluorescence emission spectra of HSA. The complexes were also screened for their DNA binding propensity through UV-vis absorption titration, circular dichroism and fluorescence spectral studies. Results show that they effectively interact with CT-DNA through an intercalative mode of binding, with binding constants ranging from 103 to 104 M-1. Among the three complexes 1 has the highest binding affinity towards CT-DNA. Further, the phosphatase activity was evaluated using bis(2,4-dinitrophenyl)phosphate (BDNPP) as substrate, however, the complexes did not yield any measurable catalytic activity. Nevertheless the complexes showed significant cytotoxic potential against HeLa and HT-29 cancer cell lines that was assessed through MTT assay and DAPI staining. Remarkably, complex 1 showed better activity than cisplatin against HT-29 cell line.

Keywords: Cytotoxicity; DNA and HSA interaction; Phosphoesterase activity; Polynuclear zinc(II) complexes; Thiosemicarbazone.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Albumins / chemistry
  • Albumins / metabolism
  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / toxicity
  • Coordination Complexes / chemical synthesis*
  • Coordination Complexes / toxicity
  • DNA / chemistry
  • HT29 Cells
  • HeLa Cells
  • Humans
  • Organometallic Compounds / chemical synthesis*
  • Organometallic Compounds / toxicity
  • Phosphoric Monoester Hydrolases / chemistry
  • Protein Binding
  • Thiosemicarbazones / chemistry*
  • Zinc / chemistry*

Substances

  • Albumins
  • Antineoplastic Agents
  • Coordination Complexes
  • Organometallic Compounds
  • Thiosemicarbazones
  • DNA
  • Phosphoric Monoester Hydrolases
  • Zinc