Solid phase combinatorial synthesis of benzothiazoles and evaluation of topoisomerase II inhibitory activity

Suk June Choi; Hyen Joo Park; Sang Kook Lee; Sang Woong Kim; Gyoonhee Han; Hea Young Park Choo

doi:10.1016/j.bmc.2005.09.051

Solid phase combinatorial synthesis of benzothiazoles and evaluation of topoisomerase II inhibitory activity

Suk June Choi, Hyen Joo Park, Sang Kook Lee, Sang Woong Kim, Gyoonhee Han, Hea Young Park Choo

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109 Citations (Scopus)

Abstract

To investigate one possible mechanism of action of the cytotoxic activity of benzothiazoles, we synthesized 2-(substituted-phenyl)benzothiazoles and evaluated their ability to inhibit topoisomerase II activities. Solid phase combinatorial method using trityl resin was employed and benzothiazole derivatives with various substitution on 2′-, 3′-, or 4′-position of phenyl group were obtained in ca. 30 mg scale (7-96% yield). Most of the compounds synthesized exhibited topoisomerase II inhibitory activity at 100 μM. 2-(3-Amino-4-methylphenyl)benzothiazole showed high activity (IC₅₀ = 71.7 μM), comparable to etoposide (IC ₅₀ = 78.4 μM).

Original language	English
Pages (from-to)	1229-1235
Number of pages	7
Journal	Bioorganic and Medicinal Chemistry
Volume	14
Issue number	4
DOIs	https://doi.org/10.1016/j.bmc.2005.09.051
Publication status	Published - 2006 Feb 15

Bibliographical note

Funding Information:
This work was supported by Grant No. 2000-0-215-001-3 from the Basic Research Program of the Korea Science and Engineering Foundation and M10310200002-03B4620-00200 from Korea Institute of Science & Technology Evaluation and Planning.

All Science Journal Classification (ASJC) codes

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

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10.1016/j.bmc.2005.09.051

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title = "Solid phase combinatorial synthesis of benzothiazoles and evaluation of topoisomerase II inhibitory activity",

abstract = "To investigate one possible mechanism of action of the cytotoxic activity of benzothiazoles, we synthesized 2-(substituted-phenyl)benzothiazoles and evaluated their ability to inhibit topoisomerase II activities. Solid phase combinatorial method using trityl resin was employed and benzothiazole derivatives with various substitution on 2′-, 3′-, or 4′-position of phenyl group were obtained in ca. 30 mg scale (7-96% yield). Most of the compounds synthesized exhibited topoisomerase II inhibitory activity at 100 μM. 2-(3-Amino-4-methylphenyl)benzothiazole showed high activity (IC50 = 71.7 μM), comparable to etoposide (IC 50 = 78.4 μM).",

author = "Choi, {Suk June} and Park, {Hyen Joo} and Lee, {Sang Kook} and Kim, {Sang Woong} and Gyoonhee Han and Choo, {Hea Young Park}",

note = "Funding Information: This work was supported by Grant No. 2000-0-215-001-3 from the Basic Research Program of the Korea Science and Engineering Foundation and M10310200002-03B4620-00200 from Korea Institute of Science & Technology Evaluation and Planning. ",

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AU - Choi, Suk June

AU - Park, Hyen Joo

AU - Lee, Sang Kook

AU - Kim, Sang Woong

AU - Han, Gyoonhee

AU - Choo, Hea Young Park

N1 - Funding Information: This work was supported by Grant No. 2000-0-215-001-3 from the Basic Research Program of the Korea Science and Engineering Foundation and M10310200002-03B4620-00200 from Korea Institute of Science & Technology Evaluation and Planning.

PY - 2006/2/15

Y1 - 2006/2/15

N2 - To investigate one possible mechanism of action of the cytotoxic activity of benzothiazoles, we synthesized 2-(substituted-phenyl)benzothiazoles and evaluated their ability to inhibit topoisomerase II activities. Solid phase combinatorial method using trityl resin was employed and benzothiazole derivatives with various substitution on 2′-, 3′-, or 4′-position of phenyl group were obtained in ca. 30 mg scale (7-96% yield). Most of the compounds synthesized exhibited topoisomerase II inhibitory activity at 100 μM. 2-(3-Amino-4-methylphenyl)benzothiazole showed high activity (IC50 = 71.7 μM), comparable to etoposide (IC 50 = 78.4 μM).

AB - To investigate one possible mechanism of action of the cytotoxic activity of benzothiazoles, we synthesized 2-(substituted-phenyl)benzothiazoles and evaluated their ability to inhibit topoisomerase II activities. Solid phase combinatorial method using trityl resin was employed and benzothiazole derivatives with various substitution on 2′-, 3′-, or 4′-position of phenyl group were obtained in ca. 30 mg scale (7-96% yield). Most of the compounds synthesized exhibited topoisomerase II inhibitory activity at 100 μM. 2-(3-Amino-4-methylphenyl)benzothiazole showed high activity (IC50 = 71.7 μM), comparable to etoposide (IC 50 = 78.4 μM).

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Solid phase combinatorial synthesis of benzothiazoles and evaluation of topoisomerase II inhibitory activity

Abstract

Bibliographical note

All Science Journal Classification (ASJC) codes

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