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).
Bibliographical noteFunding 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
- Molecular Medicine
- Molecular Biology
- Pharmaceutical Science
- Drug Discovery
- Clinical Biochemistry
- Organic Chemistry