Design, synthesis, and biological evaluation of prazosin-related derivatives as multipotent compounds.
To combine in the same molecule alpha(1)-adrenoreceptor blocking and antioxidant properties, compounds 2-5 were designed and synthesized. All compounds were effective alpha(1)-adrenoreceptor antagonists and were tested in both functional and binding assays. In addition, compounds 2 and 5 also displayed significant capacity to inhibit intracellular oxidative stress, whereas 3-5 exerted potent antiproliferative activity in lymph node carcinoma of prostate cells.
Antonello
Alessandra
A
Departments of Pharmaceutical Sciences, Alma Mater Studiorum, University of Bologna, Via Belmeloro 6, 40126 Bologna, Italy.
Hrelia
Patrizia
P
Leonardi
Amedeo
A
Marucci
Gabriella
G
Rosini
Michela
M
Tarozzi
Andrea
A
Tumiatti
Vincenzo
V
Melchiorre
Carlo
C
D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D001671:Biochemistry / Q000379:methods; D016466:CHO Cells; D002277:Carcinoma / Q000188:drug therapy; D006224:Cricetinae; D003412:Cricetulus; D015195:Drug Design; D004353:Drug Evaluation, Preclinical / Q000379:methods; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D011224:Prazosin / Q000031:analogs & derivatives* / Q000737:chemistry; D011471:Prostatic Neoplasms / Q000188:drug therapy; D051381:Rats; D017382:Reactive Oxygen Species; D018340:Receptors, Adrenergic, alpha-1 / Q000235:genetics / Q000378:metabolism; D013329:Structure-Activity Relationship; D008063:Thioctic Acid / Q000737:chemistry / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014649:Vas Deferens / Q000187:drug effects
D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists; D000975:Antioxidants; D017382:Reactive Oxygen Species; D018340:Receptors, Adrenergic, alpha-1; D008063:Thioctic Acid; D011224:Prazosin