Design, synthesis, and biological evaluation of combretabenzodiazepines: a novel class of anti-tubulin agents

  • J Med Chem. 2015 Feb 12;58(3):1345-57. doi: 10.1021/jm5016389.
Ubaldina Galli  1 ,  Cristina Travelli ,  Silvio Aprile ,  Elena Arrigoni ,  Simone Torretta ,  Giorgio Grosa ,  Alberto Massarotti ,  Giovanni Sorba ,  Pier Luigi Canonico ,  Armando A Genazzani ,  Gian Cesare Tron
Affiliations
  • 1. Dipartimento di Scienze del Farmaco, Università degli Studi del Piemonte Orientale "A. Avogadro" , Largo Donegani 2, 28100 Novara, Italy.
PMID: 25584687 DOI: 10.1021/jm5016389
Abstract

In the present manuscript, starting from the 1,4-benzodiazepin-2-one nucleus, a privileged structure in medicinal chemistry, we have synthesized a novel class of cis-locked combretastatins named combreatabenzodiazepines. They show similar cytotoxic and antitubulin activity compared to combretastatin A-4 in neuroblastoma cells, showing a better pharmacokinetic profile. This class of compounds has therefore the potential for further development as antitubulin agents.