title: Antimitotic and vascular disrupting agents: 2-hydroxy-3,4,5-trimethoxybenzophenones.
abstract: 2-Hydroxy-3,4,5-trimethoxybenzophenones (8-16) manifest pseudo-ring formation involving intramolecular hydrogen bonding of the 2-OH and the carbonyl group. Among the synthetic products described in this report, (3-hydroxy-4-methoxyphenyl)(2-hydroxy-3,4,5-trimethoxyphenyl)-methanone (14) and (3-amino-4-methoxyphenyl)(2-hydroxy-3,4,5-trimethoxy-phenyl)methanone (16) exhibit significant antiproliferative activity against KB cells with IC50 values of 11.1 and 11.3 nM, respectively. These two compounds also displayed tubulin affinity comparable to that of combretastatin A-4. In studies with human umbilical vein endothelial cells, compounds 14 and 16 revealed concentration-dependent vascular-disrupting properties. The results support the rationale of the pseudo-ring concept and suggest further investigation of A-ring modification in these benzophenones.
authors.affiliation: School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei 11031, Taiwan, ROC.
authors.forename: Chih-Yi
authors.initials: CY
authors.lastname: Chang
authors.affiliation: School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei 11031, Taiwan, ROC.
authors.forename: Hsun-Yueh
authors.initials: HY
authors.lastname: Chuang
authors.affiliation: School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei 11031, Taiwan, ROC.
authors.forename: Hsueh-Yun
authors.initials: HY
authors.lastname: Lee
authors.affiliation: Institute of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Miaoli 350, Taiwan, ROC.
authors.forename: Teng-Kuang
authors.initials: TK
authors.lastname: Yeh
authors.affiliation: Institute of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Miaoli 350, Taiwan, ROC.
authors.forename: Ching-Chuan
authors.initials: CC
authors.lastname: Kuo
authors.affiliation: National Institute of Cancer Research, National Health Research Institutes, Tainan 70456, Taiwan, ROC.
authors.forename: Chi-Yen
authors.initials: CY
authors.lastname: Chang
authors.affiliation: National Institute of Cancer Research, National Health Research Institutes, Tainan 70456, Taiwan, ROC; Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan, ROC. Electronic address: jychang@nhri.org.tw.
authors.forename: Jang-Yang
authors.initials: JY
authors.lastname: Chang
authors.affiliation: School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei 11031, Taiwan, ROC; School of Pharmacy, National Defense Medical Center, 161 Minchuan East Road, Section 6, Taipei 114, Taiwan, ROC. Electronic address: jpl@tmu.edu.tw.
authors.forename: Jing-Ping
authors.initials: JP
authors.lastname: Liou
mesh_terms: D050256:Antimitotic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001577:Benzophenones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003078:Colchicine / Q000037:antagonists & inhibitors; D004305:Dose-Response Relationship, Drug; D019073:HT29 Cells; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects*; D006801:Humans; D007624:KB Cells; D015394:Molecular Structure; D058105:Polymerization / Q000187:drug effects; D013329:Structure-Activity Relationship; D014404:Tubulin / Q000378:metabolism
chemical_list: C000593389:(3-amino-4-methoxyphenyl)(2-hydroxy-3,4,5-trimethoxyphenyl)methanone; C000593388:(3-hydroxy-4-methoxyphenyl)(2-hydroxy-3,4,5-trimethoxyphenyl)methanone; D050256:Antimitotic Agents; D001577:Benzophenones; D014404:Tubulin; D003078:Colchicine
keywords: Antiproliferative; CA-4; Vascular-disrupting agents