Inhibitory activities against topoisomerase I and II by isoaurostatin derivatives and their structure-activity relationships

Keitarou Suzuki, Tadashi Okawara, Tatuya Higashijima, Kazumi Yokomizo, Tohru Mizushima, Masami Otsuka

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Isoaurostatin A (IAS-A) isolated from Thermomonospora alba showed weak inhibition against topoisomerase (topo) I (IC50 = 307 μM). To get more strong inhibition, derivatives of IAS-A were prepared and their structure-activity relationships against topo I and II were investigated. The addition of hydroxyl group on aromatic rings increased the activities, 3-(3,4,5-trihydroxybenzylidene)-5-hydroxy-3H-benzofuran-2-one (IAS-9) showed strong inhibition (IC50 = 3 μM) against topo I. And also, the increasing of hydroxyl group increased growth inhibition against a variety of cancer cells, and IAS-9 showed most potent inhibition. Unlike camptothecin and etoposide, IAS-9 neither stabilized DNA-topo cleavable complex nor intercalated into DNA, and it inhibited topo I and II noncompetitively. The inhibitory activities also increased by opening of lactone ring in the molecule of IAS-9.

Original languageEnglish
Pages (from-to)2065-2068
Number of pages4
JournalBioorganic and Medicinal Chemistry Letters
Volume15
Issue number8
DOIs
Publication statusPublished - 2005 Apr 15
Externally publishedYes

Fingerprint

Type II DNA Topoisomerase
Type I DNA Topoisomerase
Structure-Activity Relationship
Derivatives
Hydroxyl Radical
Inhibitory Concentration 50
Camptothecin
Lactones
Etoposide
Cells
isoaurostatin
Molecules
DNA
Growth
Neoplasms

Keywords

  • Anticancer
  • Isoaurostatin
  • Structure-activity relationship
  • Topoisomerase

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Organic Chemistry
  • Drug Discovery
  • Pharmaceutical Science

Cite this

Inhibitory activities against topoisomerase I and II by isoaurostatin derivatives and their structure-activity relationships. / Suzuki, Keitarou; Okawara, Tadashi; Higashijima, Tatuya; Yokomizo, Kazumi; Mizushima, Tohru; Otsuka, Masami.

In: Bioorganic and Medicinal Chemistry Letters, Vol. 15, No. 8, 15.04.2005, p. 2065-2068.

Research output: Contribution to journalArticle

Suzuki, Keitarou ; Okawara, Tadashi ; Higashijima, Tatuya ; Yokomizo, Kazumi ; Mizushima, Tohru ; Otsuka, Masami. / Inhibitory activities against topoisomerase I and II by isoaurostatin derivatives and their structure-activity relationships. In: Bioorganic and Medicinal Chemistry Letters. 2005 ; Vol. 15, No. 8. pp. 2065-2068.
@article{a707c4ebb99d4bc5aa26e88770e189db,
title = "Inhibitory activities against topoisomerase I and II by isoaurostatin derivatives and their structure-activity relationships",
abstract = "Isoaurostatin A (IAS-A) isolated from Thermomonospora alba showed weak inhibition against topoisomerase (topo) I (IC50 = 307 μM). To get more strong inhibition, derivatives of IAS-A were prepared and their structure-activity relationships against topo I and II were investigated. The addition of hydroxyl group on aromatic rings increased the activities, 3-(3,4,5-trihydroxybenzylidene)-5-hydroxy-3H-benzofuran-2-one (IAS-9) showed strong inhibition (IC50 = 3 μM) against topo I. And also, the increasing of hydroxyl group increased growth inhibition against a variety of cancer cells, and IAS-9 showed most potent inhibition. Unlike camptothecin and etoposide, IAS-9 neither stabilized DNA-topo cleavable complex nor intercalated into DNA, and it inhibited topo I and II noncompetitively. The inhibitory activities also increased by opening of lactone ring in the molecule of IAS-9.",
keywords = "Anticancer, Isoaurostatin, Structure-activity relationship, Topoisomerase",
author = "Keitarou Suzuki and Tadashi Okawara and Tatuya Higashijima and Kazumi Yokomizo and Tohru Mizushima and Masami Otsuka",
year = "2005",
month = "4",
day = "15",
doi = "10.1016/j.bmcl.2005.02.052",
language = "English",
volume = "15",
pages = "2065--2068",
journal = "Bioorganic and Medicinal Chemistry Letters",
issn = "0960-894X",
publisher = "Elsevier Limited",
number = "8",

}

TY - JOUR

T1 - Inhibitory activities against topoisomerase I and II by isoaurostatin derivatives and their structure-activity relationships

AU - Suzuki, Keitarou

AU - Okawara, Tadashi

AU - Higashijima, Tatuya

AU - Yokomizo, Kazumi

AU - Mizushima, Tohru

AU - Otsuka, Masami

PY - 2005/4/15

Y1 - 2005/4/15

N2 - Isoaurostatin A (IAS-A) isolated from Thermomonospora alba showed weak inhibition against topoisomerase (topo) I (IC50 = 307 μM). To get more strong inhibition, derivatives of IAS-A were prepared and their structure-activity relationships against topo I and II were investigated. The addition of hydroxyl group on aromatic rings increased the activities, 3-(3,4,5-trihydroxybenzylidene)-5-hydroxy-3H-benzofuran-2-one (IAS-9) showed strong inhibition (IC50 = 3 μM) against topo I. And also, the increasing of hydroxyl group increased growth inhibition against a variety of cancer cells, and IAS-9 showed most potent inhibition. Unlike camptothecin and etoposide, IAS-9 neither stabilized DNA-topo cleavable complex nor intercalated into DNA, and it inhibited topo I and II noncompetitively. The inhibitory activities also increased by opening of lactone ring in the molecule of IAS-9.

AB - Isoaurostatin A (IAS-A) isolated from Thermomonospora alba showed weak inhibition against topoisomerase (topo) I (IC50 = 307 μM). To get more strong inhibition, derivatives of IAS-A were prepared and their structure-activity relationships against topo I and II were investigated. The addition of hydroxyl group on aromatic rings increased the activities, 3-(3,4,5-trihydroxybenzylidene)-5-hydroxy-3H-benzofuran-2-one (IAS-9) showed strong inhibition (IC50 = 3 μM) against topo I. And also, the increasing of hydroxyl group increased growth inhibition against a variety of cancer cells, and IAS-9 showed most potent inhibition. Unlike camptothecin and etoposide, IAS-9 neither stabilized DNA-topo cleavable complex nor intercalated into DNA, and it inhibited topo I and II noncompetitively. The inhibitory activities also increased by opening of lactone ring in the molecule of IAS-9.

KW - Anticancer

KW - Isoaurostatin

KW - Structure-activity relationship

KW - Topoisomerase

UR - http://www.scopus.com/inward/record.url?scp=15944415851&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=15944415851&partnerID=8YFLogxK

U2 - 10.1016/j.bmcl.2005.02.052

DO - 10.1016/j.bmcl.2005.02.052

M3 - Article

C2 - 15808469

AN - SCOPUS:15944415851

VL - 15

SP - 2065

EP - 2068

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

SN - 0960-894X

IS - 8

ER -