title: Antimitotic and antivascular activity of heteroaroyl-2-hydroxy-3,4,5-trimethoxybenzenes.
abstract: This study reports the synthesis of a series of heteroaroyl-2-hydroxy-3,4,5-trimethoxybenzenes, which are potent antitubulin agents. Compound 13, (2-hydroxy-3,4,5-trimethoxyphenyl)-(6-methoxy-1H-indol-3-yl)-methanone exhibits marked antiproliferative activity against KB and MKN45 cells with IC50 values of 8.8 and 10.5 nM, respectively, binds strongly to the colchicine binding site and leads to inhibition of tubulin polymerization. It also behaves as a vascular disrupting agent which suppresses the formation of capillaries. The C2-OH group in the A-ring of this compound not only retains the biological activity but has valuable physicochemical properties.
authors.affiliation: School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei 11031, Taiwan.
authors.forename: Hsueh-Yun
authors.initials: HY
authors.lastname: Lee
authors.affiliation: School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei 11031, Taiwan.
authors.forename: Chih-Yi
authors.initials: CY
authors.lastname: Chang
authors.affiliation: Center for Translational Medicine, Taipei Medical University, Taiwan.
authors.forename: Mei-Jung
authors.initials: MJ
authors.lastname: Lai
authors.affiliation: School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei 11031, Taiwan.
authors.forename: Hsun-Yueh
authors.initials: HY
authors.lastname: Chuang
authors.affiliation: Institute of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Miaoli 350, Taiwan.
authors.forename: Ching-Chuan
authors.initials: CC
authors.lastname: Kuo
authors.affiliation: National Institute of Cancer Research, National Health Research Institutes, Tainan 70456, Taiwan.
authors.forename: Chi-Yen
authors.initials: CY
authors.lastname: Chang
authors.affiliation: National Institute of Cancer Research, National Health Research Institutes, Tainan 70456, Taiwan; Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan. 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; School of Pharmacy, National Defense Medical Center, 161 Minchuan East Road, Section 6, Taipei 114, Taiwan. Electronic address: jpl@tmu.edu.tw.
authors.forename: Jing-Ping
authors.initials: JP
authors.lastname: Liou
mesh_terms: D020533:Angiogenesis Inhibitors / Q000737:chemistry / Q000494:pharmacology; D050256:Antimitotic Agents / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D001554:Benzene / Q000737:chemistry; D001665:Binding Sites; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D060326:Chemistry Techniques, Synthetic; D003078:Colchicine / Q000378:metabolism; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D019073:HT29 Cells / Q000187:drug effects; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects; D006801:Humans; D020128:Inhibitory Concentration 50; D013329:Structure-Activity Relationship; D050257:Tubulin Modulators / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology
chemical_list: D020533:Angiogenesis Inhibitors; D050256:Antimitotic Agents; D050257:Tubulin Modulators; D001554:Benzene; D003078:Colchicine
keywords: Antiproliferative; CA-4; Vascular-disrupting agents