Synthesis and structure-activity relationships of 1-benzyl-4,5,6- trimethoxyindoles as a novel class of potent antimitotic agents

Mei-Jung Lai; Ching-Chuan Kuo; Teng-Kuang Yeh; Hsing-Pang Hsieh; Li-Tzong Chen; Wen-Yu Pan; Kuang Yang Hsu; Jang-Yang Chang; Jing Ping Liou

doi:10.1002/cmdc.200800405

Synthesis and structure-activity relationships of 1-benzyl-4,5,6- trimethoxyindoles as a novel class of potent antimitotic agents

Mei-Jung Lai, Ching-Chuan Kuo, Teng-Kuang Yeh, Hsing-Pang Hsieh, Li-Tzong Chen, Wen-Yu Pan, Kuang Yang Hsu, Jang-Yang Chang, Jing Ping Liou

Research output: Contribution to journal › Article › peer-review

13 Citations (Scopus)

Abstract

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 n M, 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 μM, respectively, representing an improvement over colchicine (IG₅₀=4.3μM).

Original language	English
Pages (from-to)	588-593
Number of pages	6
Journal	ChemMedChem
Volume	4
Issue number	4
DOIs	https://doi.org/10.1002/cmdc.200800405
Publication status	Published - Apr 17 2009

Keywords

Antitumor agents
Drug design
Inhibitors
Structure-activity relationships
Tubulin polymerization

ASJC Scopus subject areas

Drug Discovery
General Pharmacology, Toxicology and Pharmaceutics
Molecular Medicine
Biochemistry
Pharmacology
Organic Chemistry

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1002/cmdc.200800405

Cite this

@article{39622decbd0c4a5cbf73ba92d2b791c4,

title = "Synthesis and structure-activity relationships of 1-benzyl-4,5,6- trimethoxyindoles as a novel class of potent antimitotic agents",

abstract = "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 n M, 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 μM, respectively, representing an improvement over colchicine (IG50=4.3μM).",

keywords = "Antitumor agents, Drug design, Inhibitors, Structure-activity relationships, Tubulin polymerization",

author = "Mei-Jung Lai and Ching-Chuan Kuo and Teng-Kuang Yeh and Hsing-Pang Hsieh and Li-Tzong Chen and Wen-Yu Pan and Hsu, {Kuang Yang} and Jang-Yang Chang and Liou, {Jing Ping}",

year = "2009",

month = apr,

day = "17",

doi = "10.1002/cmdc.200800405",

language = "English",

volume = "4",

pages = "588--593",

journal = "ChemMedChem",

issn = "1860-7179",

publisher = "John Wiley and Sons Ltd",

number = "4",

}

TY - JOUR

T1 - Synthesis and structure-activity relationships of 1-benzyl-4,5,6- trimethoxyindoles as a novel class of potent antimitotic agents

AU - Lai, Mei-Jung

AU - Kuo, Ching-Chuan

AU - Yeh, Teng-Kuang

AU - Hsieh, Hsing-Pang

AU - Chen, Li-Tzong

AU - Pan, Wen-Yu

AU - Hsu, Kuang Yang

AU - Chang, Jang-Yang

AU - Liou, Jing Ping

PY - 2009/4/17

Y1 - 2009/4/17

N2 - 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 n M, 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 μM, respectively, representing an improvement over colchicine (IG50=4.3μM).

AB - 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 n M, 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 μM, respectively, representing an improvement over colchicine (IG50=4.3μM).

KW - Antitumor agents

KW - Drug design

KW - Inhibitors

KW - Structure-activity relationships

KW - Tubulin polymerization

UR - http://www.scopus.com/inward/record.url?scp=65549144450&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=65549144450&partnerID=8YFLogxK

U2 - 10.1002/cmdc.200800405

DO - 10.1002/cmdc.200800405

M3 - Article

C2 - 19266513

AN - SCOPUS:65549144450

SN - 1860-7179

VL - 4

SP - 588

EP - 593

JO - ChemMedChem

JF - ChemMedChem

IS - 4

ER -

Synthesis and structure-activity relationships of 1-benzyl-4,5,6- trimethoxyindoles as a novel class of potent antimitotic agents

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this