Bis(pentafluorosulfanyl)phenyl azide as an expeditious tool for click chemistry toward antitumor pharmaceuticals

ChemMedChem. 2014 May;9(5):913-7. doi: 10.1002/cmdc.201400059. Epub 2014 Mar 3.

Abstract

The inclusion of fluorine in pharmaceutical agents is a well- established means of improving their druglike properties. Different substituents have been used to introduce fluorine, including trifluoromethyl and trifluoromethylthio groups; however, the pentafluorosulfanyl remains relatively underutilized although it is considered to be a "super" trifluoromethyl group. Here, a series of pentafluorosulfanyl-containing 1,4-disubstituted-1,2,3-triazoles were synthesized by click reaction from alkynes and 3,5-bis(pentafluorosulfanyl)phenyl azide in excellent yields. Their biological activities were evaluated against human leukemic monocyte lymphoma U937 cells. In particular, 1-(3,5-bis(pentafluorosulfanyl)phenyl)-4-(4-fluorophenyl)-1H-1,2,3-triazole exhibited potent efficacy in cell viability assays at a concentration of 60 μM and was shown to activate caspase-3 activity, indicating induction of apoptosis. An analogous fluorenol-substituted triazole also exhibited promising cytotoxic effects against U937 cells, with an IC50 value of 6.29 μM. Given these preliminary results, these pentafluorosulfanyl-containing triazoles represent useful building blocks for the further development of novel antitumor agents.

Keywords: antitumor agents; apoptosis; necrosis; pentafluorosulfanyl group; triazoles.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Apoptosis / drug effects
  • Azides / chemistry*
  • Caspase 3 / metabolism
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Click Chemistry / methods*
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Humans
  • Molecular Structure
  • Structure-Activity Relationship
  • Sulfides / chemistry*
  • U937 Cells

Substances

  • Antineoplastic Agents
  • Azides
  • Sulfides
  • Caspase 3