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

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 11 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 11 inhibitory activity at 100 mu M. 2-(3-Amino-4-methylphenyl)benzothiazole showed high activity (IC50 = 71.7 mu M), comparable to etoposide (IC50 = 78.4 mu M). (c) 2005 Elsevier Ltd. All rights reserved.