Synthesis, characterization, cytotoxicity, a poptosis and cell cycle arrest of dibenzoxanthenes derivatives

Spectrochim Acta A Mol Biomol Spectrosc. 2014 Dec 10:133:559-67. doi: 10.1016/j.saa.2014.05.054. Epub 2014 May 28.

Abstract

Two new dibenzoxanthenes compounds 1 and 2 have been synthesized and characterized by analytical and spectral methods. The crystal structure of compound 2 informs that the five rings of compound are almost planar. The DNA binding properties of two compounds were studied by absorption titration, viscosity measurement and luminescence. These results indicate that two compounds interact with calf thymus DNA through intercalative mode. Agarose gel electrophoresis experiment shows that PBR 322 DNA can be induced to cleave by two compounds under photoactivated condition. Compound 1 exhibits higher cytotoxicity than compound 2 toward MG-63, BEL-7402 and A549 cells. The apoptosis and cellular uptake of MG-63 cells were studied by fluorescence microscopy. Two compounds can also enhance the level of reactive oxygen species (ROS) and decrease the mitochondrial membrane potential. Compound 1 induces cell cycle arrest in G2/M phase and compound 2 induces cell cycle arrest in G0/G1 phase in MG-63.

Keywords: Apoptosis; Bibenzoxanthene; Cell cycle arrest; Cytotoxicity; DNA binding.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Cattle
  • Cell Cycle Checkpoints / drug effects
  • Cell Line, Tumor
  • DNA / metabolism
  • Humans
  • Membrane Potential, Mitochondrial / drug effects
  • Neoplasms / drug therapy
  • Neoplasms / metabolism
  • Reactive Oxygen Species / metabolism
  • Xanthenes / chemical synthesis
  • Xanthenes / chemistry*
  • Xanthenes / pharmacology*

Substances

  • Antineoplastic Agents
  • Reactive Oxygen Species
  • Xanthenes
  • dibenzoxanthenes
  • DNA
  • calf thymus DNA