title: Synthesis and structure-activity relationship of 2-aminobenzophenone derivatives as antimitotic agents.
abstract: A new type of inhibitor of tubulin polymerization was discovered on the basis of the combretastatin molecular skeleton. The lead compounds in this series, compounds 6 and 7, strongly inhibited tubulin polymerization in vitro and significantly arrested cells at the G(2)/M phase. Compounds 6 and 7 yielded 50- to 100-fold lower IC(50) values than did combretastatin A-4 against Colo 205, NUGC3, and HA22T human cancer cell lines as well as similar or greater growth inhibitory activities than did combretastain A-4 against DLD-1, HR, MCF-7, DU145, HONE-1, and MES-SA/DX5 human cancer cell lines. Structure-activity relationship information revealed that introduction of an amino group at the ortho position of the benzophenone ring plays an integral role for increased growth inhibition.
authors.affiliation: Medicinal Synthetic Laboratory, Division of Biotechnology and Pharmaceutical Research, National Health Research Institutes, 128 Yen-Chiu-Yuan Road, Sec II, Taipei 115, Taiwan, Republic of China.
authors.forename: Jing-Ping
authors.initials: JP
authors.lastname: Liou
authors.forename: Chun-Wei
authors.initials: CW
authors.lastname: Chang
authors.forename: Jeng-Shin
authors.initials: JS
authors.lastname: Song
authors.forename: Yung-Ning
authors.initials: YN
authors.lastname: Yang
authors.forename: Ching-Fang
authors.initials: CF
authors.lastname: Yeh
authors.forename: Huan-Yi
authors.initials: HY
authors.lastname: Tseng
authors.forename: Yu-Kang
authors.initials: YK
authors.lastname: Lo
authors.forename: Yi-Ling
authors.initials: YL
authors.lastname: Chang
authors.forename: Chung-Ming
authors.initials: CM
authors.lastname: Chang
authors.forename: Hsing-Pang
authors.initials: HP
authors.lastname: Hsieh
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001577:Benzophenones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001667:Binding, Competitive; D001704:Biopolymers; D003078:Colchicine / Q000737:chemistry; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008938:Mitosis / Q000187:drug effects; D012995:Solubility; D013329:Structure-Activity Relationship; D014404:Tubulin / Q000737:chemistry; D014407:Tumor Cells, Cultured
chemical_list: C458043:(2-amino-4-methoxyphenyl)(3,4,5-trimethoxyphenyl)methanone; C458044:(2-amino-5-methoxyphenyl)(3,4,5-trimethoxyphenyl)methanone; D000970:Antineoplastic Agents; D001577:Benzophenones; D001704:Biopolymers; D014404:Tubulin; D003078:Colchicine