Syntheses and potential anti-prostate cancer activities of ionone-based chalcones.
We report the SAR studies of 43 ionone-based chalcones that demonstrate substantial in vitro anti-proliferative activities in LNCaP, MDA-PCa-2b, 22Rv1, C4-2B and PC-3 prostate cancer cell lines. Compound 25 with an IC(50) value of 0.74 microM in LNCaP cells potently antagonizes DHT-induced transactivation of the wild type and the clinically relevant T877A, W741C and H874Y mutated androgen receptors, representing a novel chalcone as pan-antagonist of androgen receptor.
Zhou
Jinming
J
Department of Oncology, McGill University, Montreal, Canada.
Geng
Guoyan
G
Batist
Gerald
G
Wu
Jian Hui
JH
D059002:Androgen Receptor Antagonists; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D047188:Chalcones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D020650:Combinatorial Chemistry Techniques; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008297:Male; D051379:Mice; D015394:Molecular Structure; D009154:Mutation; D045792:Norisoprenoids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D011471:Prostatic Neoplasms / Q000188:drug therapy*; D011944:Receptors, Androgen / Q000235:genetics; D013329:Structure-Activity Relationship
D059002:Androgen Receptor Antagonists; D000970:Antineoplastic Agents; D047188:Chalcones; D045792:Norisoprenoids; D011944:Receptors, Androgen