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

doi:10.1016/j.bmcl.2005.02.052

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 journal › Article › peer-review

25 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 language	English
Pages (from-to)	2065-2068
Number of pages	4
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	15
Issue number	8
DOIs	https://doi.org/10.1016/j.bmcl.2005.02.052
Publication status	Published - 2005 Apr 15
Externally published	Yes

Keywords

Anticancer
Isoaurostatin
Structure-activity relationship
Topoisomerase

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Molecular Biology
Pharmaceutical Science
Drug Discovery
Clinical Biochemistry
Organic Chemistry

UN SDGs

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

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10.1016/j.bmcl.2005.02.052

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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",

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day = "15",

doi = "10.1016/j.bmcl.2005.02.052",

language = "English",

volume = "15",

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journal = "Bioorganic and Medicinal Chemistry Letters",

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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

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

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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