Synthesis and Structure-Activity Relationships of 1-Benzyl-4,5,6-trimethoxyindoles as a Novel Class of Potent Antimitotic Agents

被引：12

作者：

Lai, Mei-Jung ^{[1
]}

Kuo, Ching-Chuan ^{[2
]}

Yeh, Teng-Kuang ^{[3
]}

Hsieh, Hsing-Pang ^{[3
]}

Chen, Li-Tzong ^{[2
]}

Pan, Wen-Yu ^{[2
]}

Hsu, Kuang-Yang ^{[1
]}

Chang, Jang-Yang ^{[2
,4
]}

Liou, Jing-Ping ^{[1
]}

机构：

[1] Taipei Med Univ, Coll Pharm, Taipei 110, Taiwan

[2] Natl Hlth Res Inst, Natl Inst Canc Res, Tainan 704, Taiwan

[3] Natl Hlth Res Inst, Div Biotechnol & Pharmaceut Res, Zhunan Town 350, Miaoli County, Taiwan

[4] Natl Cheng Kung Univ Hosp, Div Hematol Oncol, Dept Internal Med, Tainan 704, Taiwan

来源：

CHEMMEDCHEM | 2009年 / 4卷 / 04期

关键词：

antitumor agents; drug design; inhibitors; structure-activity relationships; tubulin polymerization; VASCULAR DISRUPTING AGENTS; INHIBIT TUBULIN POLYMERIZATION; HUMAN CANCER-CELLS; ANTITUBULIN AGENTS; BIOLOGICAL EVALUATION; ANTINEOPLASTIC AGENTS; MEDICINAL CHEMISTRY; IN-VIVO; MICROTUBULE; ANALOGS;

D O I：

10.1002/cmdc.200800405

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of 1-benzyl-4,5,6-trimethoxyindoles was designed and prepared as a novel class of potent antimitotic agents acting through the colchicine binding site of tubulin. Compounds 10 and 11 showed excellent antiproliferative activity with mean IC50 values of 26 and 27 nM, respectively, in a diverse set of human cancer lines from different organs, including a MDR+ line. They also displayed substantial antitubulin efficacy with IC50 values of 3.5 and 2.6 mu M, respectively, representing an improvement over colchicine (IC50=4.3 mu M).

引用

页码：588 / 593

页数：6

共 50 条

[31] Synthesis and structure-activity relationships of novel antiseptics
Tsubouchi, H
Ohguro, K
Yasumura, K
Ishikawa, H
Kikuchi, M
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 1997, 7 (13) : 1721 - 1724
[32] Novel oximes having 5-benzyl-2,4-thiazolidinedione as antihyperglycemic agents: Synthesis and structure-activity relationship
Yanagisawa, H
Takamura, M
Yamada, E
Fujita, S
Fujiwara, T
Yachi, M
Isobe, A
Hagisawa, Y
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2000, 10 (04) : 373 - 375
[33] Structure-Activity Relationships of 1,3-Benzoxazole-4-carbonitriles as Novel Antifungal Agents with Potent in Vivo Efficacy
Kuroyanagi, Jun-ichi
Kanai, Kazuo
Horiuchi, Takao
Takeshita, Hiroshi
Kobayashi, Shozo
Achiwa, Issei
Yoshida, Kumi
Nakamura, Koichi
Kawakami, Katsuhiro
CHEMICAL & PHARMACEUTICAL BULLETIN, 2011, 59 (03) : 341 - 352
[34] QUANTITATIVE STRUCTURE - ACTIVITY RELATIONSHIP ANALYSIS OF COMBRETASTATINS - A CLASS OF NOVEL ANTIMITOTIC AGENTS
NANDY, P
BANERJEE, S
GAO, H
HUI, MBV
LIEN, EJ
PHARMACEUTICAL RESEARCH, 1991, 8 (06) : 776 - 781
[35] Synthesis, Biological Evaluation, and Structure-Activity Relationships of a Novel Class of Apurinic/Apyrimidinic Endonuclease 1 Inhibitors
Rai, Ganesha
Vyjayanti, Vaddadi N.
Dorjsuren, Dorjbal
Simeonov, Anton
Jadhav, Ajit
Wilson, David M., III
Maloney, David J.
JOURNAL OF MEDICINAL CHEMISTRY, 2012, 55 (07) : 3101 - 3112
[36] Synthesis and structure-activity relationships of a novel series of pyrimidines as potent inhibitors of TBK1/IKKε kinases
McIver, Edward G.
Bryans, Justin
Birchall, Kristian
Chugh, Jasveen
Drake, Thomas
Lewis, Stephen J.
Osborne, Joanne
Smiljanic-Hurley, Ela
Tsang, William
Kamal, Ahmad
Levy, Alison
Newman, Michelle
Taylor, Debra
Arthur, J. Simon C.
Clark, Kristopher
Cohen, Philip
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2012, 22 (23) : 7169 - 7173
[37] Synthesis and structure-activity relationships of novel furazan-3,4-diamide analogs as potent anti-cancer agents
Li, Wen-Shan
More, Shivaji V.
Wang, Chie-Hong
Jen, Ya Ching
Yao, Ching-Fa
Wang, Tein-Fu
Hung, Chin-Chun
Jao, Shu-Chuan
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2010, 20 (03) : 1148 - 1152
[38] Total Synthesis and Structure-Activity Relationships Study of Odilorhabdins, a New Class of Peptides Showing Potent Antibacterial Activity
Sarciaux, Matthieu
Pantel, Lucile
Midrier, Camille
Serri, Marine
Gerber, Cristelle
de Figueiredo, Renata Marcia
Campagne, Jean-Marc
Villain-Guillot, Philippe
Gualtieri, Maxime
Racine, Emilie
JOURNAL OF MEDICINAL CHEMISTRY, 2018, 61 (17) : 7814 - 7826
[39] Synthesis and structure-activity relationship of 2-aminobenzophenone derivatives as antimitotic agents.
Hsieh, HP
Liou, JP
Chang, CW
Song, JS
Yang, YN
Yeh, CF
Tseng, HY
Lo, YK
Chang, YL
ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, 2002, 224 : U19 - U19
[40] Synthesis and structure-activity relationships of novel THF 1β-metylcarbapenems -: II
Lin, YI
Bitha, P
Sakya, SM
Lang, SA
Yang, YJ
Weiss, WJ
Petersen, PJ
Bush, K
Testa, RT
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 1997, 7 (23) : 3063 - 3068

← 1 2 3 4 5 →