Synthesis and antiproliferative properties of N3/8-disubstituted 3,8-diazabicyclo[3.2.1]octane analogues of 3,8-bis[2-(3,4,5-trimethoxyphenyl)pyridin-4-yl]methyl-piperazine

  • Eur J Med Chem. 2007 Mar;42(3):293-306. doi: 10.1016/j.ejmech.2006.11.013.
Rosanna Filosa  1 ,  Antonella Peduto ,  Paolo de Caprariis ,  Carmela Saturnino ,  Michela Festa ,  Antonello Petrella ,  Amedeo Pau ,  Gérard Aimé Pinna ,  Paolo La Colla ,  Bernardetta Busonera ,  Roberta Loddo
Affiliations
  • 1. Dipartimento di Scienze Farmaceutiche, Università di Salerno, Via ponte don Melillo, 84084 Fisciano (SA), Italy. [email protected]
PMID: 17254669 DOI: 10.1016/j.ejmech.2006.11.013
Abstract

A series of novel N(3/8)-disubstituted-3,8-diazabicyclo[3.2.1]octanes in order to improve the in vitro activity of the prototype 3,8-bis[2-(3,4,5-trimethoxyphenyl)pyridyl-4-yl)methylpiperazine (1) were synthesized and evaluated by assays of growth inhibition against several tumor cell lines. Compounds 2a,b,f and m demonstrated not only growth-inhibitory activities against leukemia Cancer cells, but also fairly good activities against the growth of certain solid tumors. Among them, 2a is the most potent one with IC(50) values in the low micromolar range. Moreover, compound 2a has been selected for in vitro testing on MCF-7 cell to evaluate the mode of action of this lead compound.