Carborane-Based Analogues of 5-Lipoxygenase Inhibitors Co-inhibit Heat Shock Protein 90 in HCT116 Cells

ChemMedChem. 2019 Jan 22;14(2):255-261. doi: 10.1002/cmdc.201800651. Epub 2018 Dec 21.

Abstract

5-Lipoxygenase converts arachidonic acid into leukotrienes, which are involved in inflammation and angiogenesis. The introduction of carboranes can improve the pharmacokinetic behavior of metabolically less stable pharmaceutics. Herein we report the syntheses of several carborane-based inhibitors of the 5-lipoxygenase pathway. The isosteric replacement of phenyl rings by carboranes leads to improved cytotoxicity toward several melanoma and colon cancer cell lines. For the colon cancer cell line HCT116, the co-inhibition of heat shock protein 90 was observed.

Keywords: cancer; carboranes; heat shock protein 90; inhibitors; lipoxygenase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Boranes / chemistry*
  • Colonic Neoplasms / drug therapy
  • Colonic Neoplasms / metabolism
  • Drug Design
  • HCT116 Cells
  • HSP90 Heat-Shock Proteins / antagonists & inhibitors*
  • Humans
  • Lipoxygenase Inhibitors / chemistry*
  • Lipoxygenase Inhibitors / pharmacology*

Substances

  • Boranes
  • HSP90 Heat-Shock Proteins
  • Lipoxygenase Inhibitors