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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adrenergic alpha-1 Receptor Antagonists*
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Adrenergic alpha-Antagonists / chemical synthesis*
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Adrenergic alpha-Antagonists / metabolism
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Adrenergic alpha-Antagonists / pharmacology
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Animals
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Antineoplastic Agents / chemical synthesis*
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Antineoplastic Agents / metabolism
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Antineoplastic Agents / pharmacology
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CHO Cells
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Cell Line, Tumor
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Cricetinae
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Cricetulus
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Doxazosin / analogs & derivatives*
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Humans
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Male
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Mice
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Prostatic Neoplasms / drug therapy*
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Prostatic Neoplasms / pathology
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Rats
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Structure-Activity Relationship
Substances
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Adrenergic alpha-1 Receptor Antagonists
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Adrenergic alpha-Antagonists
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Antineoplastic Agents
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Doxazosin