New Oxidovanadium Complexes Incorporating Thiosemicarbazones and 1, 10-Phenanthroline Derivatives as DNA Cleavage, Potential Anticancer Agents, and Hydroxyl Radical Scavenger

Chem Biol Drug Des. 2015 Oct;86(4):926-37. doi: 10.1111/cbdd.12535. Epub 2015 Mar 9.

Abstract

Four novel oxidovanadium(IV) complexes, [VO(hntdtsc)(PHIP)] (1) (hntdtsc = 2-hydroxy-1-naphthaldehyde thiosemicarbazone, PHIP= 2-phenyl-imidazo[4,5-f]1,10-phenanthroline), [VO(hntdtsc)(DPPZ)](2)(DPPZ= dipyrido[3,2-a:2',3'-c]phenazine), [VO(satsc)(PHIP)](3) (satsc=salicylaldehyde thiosemicarbazone), and [VO(satsc)(DPPZ)](4), have been prepared and characterized. The chemical nuclease activities and photocleavage reactions of the complexes were tested. All four complexes can efficiently cleave pBR322 DNA, and complex 1 has the best cleaving ability. The antitumor properties of these complexes were examined with three different tumor cell lines using MTT assay. Their antitumor mechanism has been analyzed using cell cycle analysis, fluorescence microscopy of apoptosis, and Annexin V-FITC/PI assay. The results showed that the growth of human neuroblastoma (SH-SY5Y, SK-N-SH) and human breast adenocarcinoma (MCF-7) cells were inhibited significantly with very low IC50 values. Complex 1 was found to be the most potent antitumor agent among the four complexes. It can cause G0/G1 phase arrest of the cell cycle and exhibited significant induced apoptosis in SK-N-SH cells and displayed typical morphological apoptotic characteristics. In addition, they all displayed reasonable abilities to scavenge hydroxyl radical, and complex 1 was the best inhibitor.

Keywords: DNA cleavage; antiproliferative activities; apoptosis; hydroxyl radical; oxidovanadium complexes.

Publication types

  • Letter
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / pharmacology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • DNA Cleavage / drug effects
  • Free Radical Scavengers / chemistry
  • Free Radical Scavengers / pharmacology
  • Humans
  • Hydroxyl Radical / metabolism
  • Neoplasms / drug therapy
  • Neoplasms / genetics
  • Neoplasms / metabolism
  • Phenanthrolines / chemistry
  • Phenanthrolines / pharmacology
  • Thiosemicarbazones / chemistry*
  • Thiosemicarbazones / pharmacology*
  • Vanadates / chemistry*
  • Vanadates / pharmacology*

Substances

  • Antineoplastic Agents
  • Free Radical Scavengers
  • Phenanthrolines
  • Thiosemicarbazones
  • oxovanadium IV
  • Hydroxyl Radical
  • Vanadates
  • 1,10-phenanthroline