Synthesis and induction of G0-G1 phase arrest with apoptosis of 3,5-dimethyl-6-phenyl-8-(trifluoromethyl)-5,6-dihydropyrazolo[3,4-f][1,2,3,5]tetrazepin-4(3H)-one

Eur J Med Chem. 2008 Nov;43(11):2386-94. doi: 10.1016/j.ejmech.2008.01.007. Epub 2008 Jan 25.

Abstract

The multistep synthesis of 3,5-dimethyl-6-phenyl-8-(trifluoromethyl)-5,6-dihydropyrazolo[3,4-f][1,2,3,5]tetrazepin-4(3H)-one 15 has been carried out. The compound showed antiproliferative and apoptotic effects against K562, K562-R (imatinib mesilate resistant), HL60 and multidrug resistant (MDR) HL60 cell lines. Compound 15 showed a pro-apoptotic activity against HL60 and K562 resistant cell lines markedly higher than etoposide and busulfan, respectively. Flow cytometry studies carried out on K562 cells allowed to establish that 15 induces G0-G1 phase arrest followed by apoptosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects*
  • Azepines / chemical synthesis*
  • Azepines / chemistry
  • Azepines / pharmacology*
  • G1 Phase / drug effects*
  • HL-60 Cells
  • Humans
  • K562 Cells
  • Molecular Structure
  • Pyrazoles / chemical synthesis*
  • Pyrazoles / chemistry
  • Pyrazoles / pharmacology*
  • Resting Phase, Cell Cycle / drug effects*

Substances

  • 3,5-dimethyl-6-phenyl-8-(trifluoromethyl)-5,6-dihydropyrazolo(3,4-f)(1,2,3,5)tetrazepin-4(3H)-one
  • Azepines
  • Pyrazoles