New adamantane phenylalkylamines with σ-receptor binding affinity and anticancer activity, associated with putative antagonism of neuropathic pain

  • J Med Chem. 2012 Nov 26;55(22):10241-61. doi: 10.1021/jm3013008.
Stefanos Riganas  1 ,  Ioannis Papanastasiou ,  George B Foscolos ,  Andrew Tsotinis ,  Guillaume Serin ,  Jean-François Mirjolet ,  Kostas Dimas ,  Vassilios N Kourafalos ,  Andreas Eleutheriades ,  Vassilios I Moutsos ,  Humaira Khan ,  Stavroula Georgakopoulou ,  Angeliki Zaniou ,  Margarita Prassa ,  Maria Theodoropoulou ,  Athanasios Mantelas ,  Stavroula Pondiki ,  Alexandre Vamvakides
Affiliations
  • 1. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, National and Kapodistrian University of Athens, Panepistimioupoli-Zografou, 15771 Athens, Greece.
PMID: 23094992 DOI: 10.1021/jm3013008
Abstract

The synthesis of the adamantane phenylalkylamines 2a-d, 3a-c, and 4a-e is described. These compounds exhibited significant antiproliferative activity, in vitro, against eight Cancer cell lines tested. The σ(1), σ(2), and Sodium Channel binding affinities of compounds 2a, 3a, 4a, and 4c-e were investigated. The most interesting analogue, 4a, exhibited significant in vivo Anticancer profile on pancreas, prostate, leukemia, and ovarian Cancer cell line xenografts together with Apoptosis and Caspase-3 activation. Inhibition of the Cancer cells cycle at the sub-G1 level was also obtained with 4a. Finally, encouraging results were observed with 4a in vivo on mice, suggesting putative antimetastatic and analgesic activities of this compound.