Doxazosin-related alpha1-adrenoceptor antagonists with prostate antitumor activity.

Doxazosin analogues 1−3 and 1a were synthesized and investigated at α1-adrenoceptors and PC-3, DU-145, and LNCaP human prostate cancer cells. Compound 1 (cyclodoxazosin) was a potent α1B-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.