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 microM. 2-(3-Amino-4-methylphenyl)benzothiazole showed high activity (IC(50) = 71.7 microM), comparable to etoposide (IC(50) = 78.4 microM).
authors.affiliation: Ewha Womans University, School of Pharmacy, Seoul, Republic of Korea.
authors.forename: Suk-June
authors.initials: SJ
authors.lastname: Choi
authors.forename: Hyen Joo
authors.initials: HJ
authors.lastname: Park
authors.forename: Sang Kook
authors.initials: SK
authors.lastname: Lee
authors.forename: Sang Woong
authors.initials: SW
authors.lastname: Kim
authors.forename: Gyoonhee
authors.initials: G
authors.lastname: Han
authors.forename: Hea-Young Park
authors.initials: HY
authors.lastname: Choo
mesh_terms: D052160:Benzothiazoles; D002384:Catalysis; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D020650:Combinatorial Chemistry Techniques; D004250:DNA Topoisomerases, Type II / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity; D006801:Humans; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D059005:Topoisomerase II Inhibitors
chemical_list: D052160:Benzothiazoles; D004791:Enzyme Inhibitors; D013844:Thiazoles; D059005:Topoisomerase II Inhibitors; D004250:DNA Topoisomerases, Type II; C005465:benzothiazole