The design of a novel near-infrared fluorescent HDAC inhibitor and image of tumor cells

Bioorg Med Chem. 2020 Sep 1;28(17):115639. doi: 10.1016/j.bmc.2020.115639. Epub 2020 Jul 10.

Abstract

Histone deacetylases (HDACs) have been found to be biomarkers of cancers and the corresponding inhibitors have attracted much attention these years. Herein we reported a near-infrared fluorescent HDAC inhibitor based on vorinostat (SAHA) and a NIR fluorophore. This newly designed inhibitor showed similar inhibitory activity to SAHA against three HDAC isoforms (HDAC1, 3, 6). The western blot assay showed significant difference in compared with the negative group. When used as probe for further kinematic imaging, Probe 1 showed enhanced retention in tumor cells and the potential of HDAC inhibitors in drug delivery was firstly brought out. The cytotoxicity assay showed Probe 1 had some anti-proliferation activities with corresponding IC50 values of 9.20 ± 0.96 μM on Hela cells and 5.91 ± 0.57 μM on MDA-MB-231 cells. These results indicated that Probe 1 could be used as a potential NIR fluorescent in the study of HDAC inhibitors and lead compound for the development of visible drugs.

Keywords: HDAC; NIR; Probe; Tumor imaging.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Drug Design*
  • Fluorescent Dyes / chemistry*
  • HeLa Cells
  • Histone Deacetylase Inhibitors / chemistry*
  • Histone Deacetylase Inhibitors / metabolism
  • Histone Deacetylase Inhibitors / pharmacology
  • Histone Deacetylases / chemistry
  • Histone Deacetylases / metabolism*
  • Humans
  • Isoenzymes / chemistry
  • Isoenzymes / metabolism
  • Microscopy, Fluorescence
  • Vorinostat / chemistry

Substances

  • Fluorescent Dyes
  • Histone Deacetylase Inhibitors
  • Isoenzymes
  • Vorinostat
  • Histone Deacetylases