Structure-activity relationship study of gatastatin based on the TOPLISS tree approach

Ichiro Hayakawa, Shuya Shioda, Takumi Chinen, Takeo Usui, Hideo Kigoshi

Research output: Contribution to journalArticle

Abstract

- Various analogues of gatastatin, a y-tubulin-specific inhibitor, were designed and synthesized by systematically optimizing the aromatic ring at the 07-benzyl group in accordance with an operational Topliss tree, and their biological activities were evaluated. Some derivatives showed stronger cytotoxicity against HeLa cells than gatastatin. Especially, the cytotoxicity of the meta-chloro derivative was about 18-fold stronger than that of gatastatin. However, these derivatives did not exhibit binding ability to the yeast y-tubulin small complex or inhibitory activity against a,ß-tubulin polymerization. These results suggested that y-tubulin strongly recognized the unsubstituted phenyl ring of the 07-benzyl group in gatastatin.

Original languageEnglish
Pages (from-to)238-247
Number of pages10
JournalHeterocycles
DOIs
Publication statusPublished - Jan 1 2019

Fingerprint

Structure-Activity Relationship
Tubulin
Cytotoxicity
Tubulin Modulators
Derivatives
HeLa Cells
Polymerization
Yeasts
Bioactivity
Yeast

ASJC Scopus subject areas

  • Analytical Chemistry
  • Pharmacology
  • Organic Chemistry

Cite this

Structure-activity relationship study of gatastatin based on the TOPLISS tree approach. / Hayakawa, Ichiro; Shioda, Shuya; Chinen, Takumi; Usui, Takeo; Kigoshi, Hideo.

In: Heterocycles, 01.01.2019, p. 238-247.

Research output: Contribution to journalArticle

Hayakawa, Ichiro ; Shioda, Shuya ; Chinen, Takumi ; Usui, Takeo ; Kigoshi, Hideo. / Structure-activity relationship study of gatastatin based on the TOPLISS tree approach. In: Heterocycles. 2019 ; pp. 238-247.
@article{e44df29a8ac14ad89cef9eb2845dd6d6,
title = "Structure-activity relationship study of gatastatin based on the TOPLISS tree approach",
abstract = "- Various analogues of gatastatin, a y-tubulin-specific inhibitor, were designed and synthesized by systematically optimizing the aromatic ring at the 07-benzyl group in accordance with an operational Topliss tree, and their biological activities were evaluated. Some derivatives showed stronger cytotoxicity against HeLa cells than gatastatin. Especially, the cytotoxicity of the meta-chloro derivative was about 18-fold stronger than that of gatastatin. However, these derivatives did not exhibit binding ability to the yeast y-tubulin small complex or inhibitory activity against a,{\ss}-tubulin polymerization. These results suggested that y-tubulin strongly recognized the unsubstituted phenyl ring of the 07-benzyl group in gatastatin.",
author = "Ichiro Hayakawa and Shuya Shioda and Takumi Chinen and Takeo Usui and Hideo Kigoshi",
year = "2019",
month = "1",
day = "1",
doi = "10.3987/COM-18-S(F)16",
language = "English",
pages = "238--247",
journal = "Heterocycles",
issn = "0385-5414",
publisher = "Japan Institute of Heterocyclic Chemistry",

}

TY - JOUR

T1 - Structure-activity relationship study of gatastatin based on the TOPLISS tree approach

AU - Hayakawa, Ichiro

AU - Shioda, Shuya

AU - Chinen, Takumi

AU - Usui, Takeo

AU - Kigoshi, Hideo

PY - 2019/1/1

Y1 - 2019/1/1

N2 - - Various analogues of gatastatin, a y-tubulin-specific inhibitor, were designed and synthesized by systematically optimizing the aromatic ring at the 07-benzyl group in accordance with an operational Topliss tree, and their biological activities were evaluated. Some derivatives showed stronger cytotoxicity against HeLa cells than gatastatin. Especially, the cytotoxicity of the meta-chloro derivative was about 18-fold stronger than that of gatastatin. However, these derivatives did not exhibit binding ability to the yeast y-tubulin small complex or inhibitory activity against a,ß-tubulin polymerization. These results suggested that y-tubulin strongly recognized the unsubstituted phenyl ring of the 07-benzyl group in gatastatin.

AB - - Various analogues of gatastatin, a y-tubulin-specific inhibitor, were designed and synthesized by systematically optimizing the aromatic ring at the 07-benzyl group in accordance with an operational Topliss tree, and their biological activities were evaluated. Some derivatives showed stronger cytotoxicity against HeLa cells than gatastatin. Especially, the cytotoxicity of the meta-chloro derivative was about 18-fold stronger than that of gatastatin. However, these derivatives did not exhibit binding ability to the yeast y-tubulin small complex or inhibitory activity against a,ß-tubulin polymerization. These results suggested that y-tubulin strongly recognized the unsubstituted phenyl ring of the 07-benzyl group in gatastatin.

UR - http://www.scopus.com/inward/record.url?scp=85069524040&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85069524040&partnerID=8YFLogxK

U2 - 10.3987/COM-18-S(F)16

DO - 10.3987/COM-18-S(F)16

M3 - Article

AN - SCOPUS:85069524040

SP - 238

EP - 247

JO - Heterocycles

JF - Heterocycles

SN - 0385-5414

ER -