Combretastatin dinitrogen-substituted stilbene analogues as tubulin-binding and vascular-disrupting agents

Research output: Contribution to journalArticle

Abstract

Several stilbenoid compounds having structural similarity to the combretastatin group of natural products and characterized by the incorporation of two nitrogen-bearing groups (amine, nitro, serinamide) have been prepared by chemical synthesis and evaluated in terms of biochemical and biological activity. The 2',3'-diamino B-ring analogue 17 demonstrated remarkable cytotoxicity against selected human cancer cell lines in vitro (average GI(50) = 13.9 nM) and also showed good activity in regard to inhibition of tubulin assembly (IC50 = 2.8 mu M). In addition, a single dose (10 mg/kg) of compound 17 caused a 40% tumor-selective blood flow shutdown in tumor-bearing SCID mice at 24 h, thus suggesting the potential value of this compound and its corresponding salt formulations as new vascular-disrupting agents.

Details

Authors
  • Rogelio Siles
  • J Freeland Ackley
  • Mallinath B Hadimani
  • John J Hall
  • Benon E Mugabe
  • Rajsekhar Guddneppanavar
  • Keith A Monk
  • Jean-Charles Chapuis
  • George R Pettit
  • David J Chaplin
  • Klaus Edvardsen
  • Mary Lynn Trawick
  • Charles M Garner
  • Kevin G Pinney
Organisations
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Immunology in the medical area
Original languageEnglish
Pages (from-to)313-320
JournalJournal of Natural Products
Volume71
Issue number3
Publication statusPublished - 2008
Publication categoryResearch
Peer-reviewedYes