Polyamine conjugation of curcumin analogues toward the discovery of mitochondria-directed neuroprotective agents

  • J Med Chem. 2010 Oct 14;53(19):7264-8. doi: 10.1021/jm100637k.
Elena Simoni  1 ,  Christian Bergamini ,  Romana Fato ,  Andrea Tarozzi ,  Sandip Bains ,  Roberto Motterlini ,  Andrea Cavalli ,  Maria Laura Bolognesi ,  Anna Minarini ,  Patrizia Hrelia ,  Giorgio Lenaz ,  Michela Rosini ,  Carlo Melchiorre
Affiliations
  • 1. Department of Pharmaceutical Sciences, University of Bologna, Via Belmeloro 6, 40126 Bologna, Italy.
PMID: 20831222 DOI: 10.1021/jm100637k
Abstract

Mitochondria-directed Antioxidants 2-5 were designed by conjugating curcumin congeners with different polyamine motifs as vehicle tools. The conjugates emerged as efficient Antioxidants in mitochondria and fibroblasts and also exerted a protecting role through heme oxygenase-1 activation. Notably, the insertion of a polyamine function into the curcumin-like moiety allowed an efficient intracellular uptake and mitochondria targeting. It also resulted in a significant decrease in the cytotoxicity effects. 2-5 are therefore promising molecules for neuroprotectant lead discovery.