title: Doxazosin-related alpha1-adrenoceptor antagonists with prostate antitumor activity.
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.
authors.affiliation: Department of Chemical Sciences, University of Camerino, Camerino, Italy. dario.giardina@unicam.it
authors.forename: Dario
authors.initials: D
authors.lastname: Giardinà
authors.forename: Daniele
authors.initials: D
authors.lastname: Martarelli
authors.forename: Gianni
authors.initials: G
authors.lastname: Sagratini
authors.forename: Piero
authors.initials: P
authors.lastname: Angeli
authors.forename: Dario
authors.initials: D
authors.lastname: Ballinari
authors.forename: Ugo
authors.initials: U
authors.lastname: Gulini
authors.forename: Carlo
authors.initials: C
authors.lastname: Melchiorre
authors.forename: Elena
authors.initials: E
authors.lastname: Poggesi
authors.forename: Pierluigi
authors.initials: P
authors.lastname: Pompei
mesh_terms: D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D016466:CHO Cells; D045744:Cell Line, Tumor; D006224:Cricetinae; D003412:Cricetulus; D017292:Doxazosin / Q000031:analogs & derivatives*; D006801:Humans; D008297:Male; D051379:Mice; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D051381:Rats; D013329:Structure-Activity Relationship
chemical_list: D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists; D000970:Antineoplastic Agents; D017292:Doxazosin