Doxazosin-related alpha1-adrenoceptor antagonists with prostate antitumor activity

  • J Med Chem. 2009 Aug 13;52(15):4951-4. doi: 10.1021/jm8016046.
Dario Giardinà  1 ,  Daniele Martarelli ,  Gianni Sagratini ,  Piero Angeli ,  Dario Ballinari ,  Ugo Gulini ,  Carlo Melchiorre ,  Elena Poggesi ,  Pierluigi Pompei
Affiliations
  • 1. Department of Chemical Sciences, University of Camerino, Camerino, Italy. [email protected]
PMID: 19719240 DOI: 10.1021/jm8016046
Abstract

Doxazosin analogues 1-3 and 1a were synthesized and investigated at alpha1-adrenoceptors and PC-3, DU-145, and LNCaP human prostate Cancer cells. Compound 1 (cyclodoxazosin) was a potent alpha(1B)-adrenoceptor antagonist displaying antiproliferative activity higher than that of doxazosin in Cancer cells in vitro and in vivo, respectively. Because of its antitumor efficacy at low concentrations, lower apoptotic activity in NHDF vs tumor cells, and antiangiogenetic effect, 1 showed a better therapeutic profile relative to doxazosin.