title: 2-amino-3,4,5-trimethoxybenzophenones as potent tubulin polymerization inhibitors.
abstract: A series of novel 2-amino-3,4,5-trimethoxybenzophenone analogues exhibited excellent activity as tubulin polymerization inhibitors by targeting the colchicine binding site of microtubules. The lead compound 17 exhibited an IC50 value of 1.6 μM, similar to that of combretastatin A-4 (IC50=1.9 μM). It also displayed remarkable anti-proliferative activity, with IC50 values ranging from 7-16 nM against a variety of human cancer cell lines and one MDR(+) cancer cell line. SAR information indicated that the introduction of an amino group at the C2 position of benzophenone ring A and the C3' position of benzophenone ring B play important roles in maximizing activity.
authors.affiliation: School of Pharmacy, College of Pharmacy, Taipei Medical University, No. 250 Wuxing Street, Taipei 11031, Taiwan, Republic of China.
authors.forename: Hsun-Yueh
authors.initials: HY
authors.lastname: Chuang
authors.forename: Jang-Yang
authors.initials: JY
authors.lastname: Chang
authors.forename: Mei-Jung
authors.initials: MJ
authors.lastname: Lai
authors.forename: Ching-Chuan
authors.initials: CC
authors.lastname: Kuo
authors.forename: Hsueh-Yun
authors.initials: HY
authors.lastname: Lee
authors.forename: Hsing-Pang
authors.initials: HP
authors.lastname: Hsieh
authors.forename: Ying-Jen
authors.initials: YJ
authors.lastname: Chen
authors.forename: Li-Tzong
authors.initials: LT
authors.lastname: Chen
authors.forename: Wen-Yu
authors.initials: WY
authors.lastname: Pan
authors.forename: Jing-Ping
authors.initials: JP
authors.lastname: Liou
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000633:toxicity; D001577:Benzophenones / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D011485:Protein Binding; D013329:Structure-Activity Relationship; D014404:Tubulin / Q000737:chemistry* / Q000378:metabolism; D050257:Tubulin Modulators / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity
chemical_list: D000970:Antineoplastic Agents; D001577:Benzophenones; D014404:Tubulin; D050257:Tubulin Modulators