title: Design, synthesis, and anti-proliferative activity of 1-(4-methoxyphenyl)-12-hydroxymethyl-p-carborane derivatives.
abstract: 1-(4-Methoxyphenyl)-12-hydroxymethyl-p-carborane (2a), which is a precursor to the previously developed potent carborane-containing ER agonist BE120, exhibited weak cell growth inhibitory activity against four human cancer cell lines (MCF-7, MDA-MB-453, LNCaP, and PC-3). The biological evaluation of a series of derivatives of 2a revealed that an increased number of methoxy groups on the benzene ring of 2a enhanced the cell growth inhibitory activity. Trimethoxyphenyl derivative 2g afforded the most potent cell growth inhibitory activity (mean GI50 value: 5.8 μM) in a panel screening using 39 human cancer cell lines. Moreover, 2g induced for MDA-MB-453 breast cancer cell lines an arrest of the cell cycle in the G2/M phase and apoptosis mediated by caspase-3/7.
authors.affiliation: Faculty of Pharmaceutical Sciences, Tohoku Medical and Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai, 981-8558, Japan.
authors.forename: Asako
authors.initials: A
authors.lastname: Kaise
authors.affiliation: Faculty of Pharmaceutical Sciences, Tohoku Medical and Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai, 981-8558, Japan. Electronic address: k-ohta@tohoku-mpu.ac.jp.
authors.forename: Kiminori
authors.initials: K
authors.lastname: Ohta
authors.affiliation: Faculty of Pharmaceutical Sciences, Tohoku Medical and Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai, 981-8558, Japan.
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Endo
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001667:Binding, Competitive; D001880:Boranes / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D060326:Chemistry Techniques, Synthetic; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D047628:Estrogen Receptor alpha / Q000378:metabolism; D006801:Humans; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D001880:Boranes; D047628:Estrogen Receptor alpha
keywords: Anti-proliferative activity; Carborane; Estrogen receptor; Panel screening