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

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Giardina D, Martarelli D, Sagratini G, Angeli P, Ballinari D, Gulini U, Melchiorre C, Poggesi E, Pompei P

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

J Med Chem. 2009 Aug 13;52(15):4951-4. doi: 10.1021/jm8016046.

PubMed ID

19719240 [ View in PubMed

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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.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Doxazosin	Alpha-1A adrenergic receptor	Ki (nM)	0.537	N/A	N/A	Details
Doxazosin	Alpha-1D adrenergic receptor	Ki (nM)	0.813	N/A	N/A	Details