alexa Dihydroxylated 2,4,6-triphenyl pyridines: synthesis, topoisomerase I and II inhibitory activity, cytotoxicity, and structure-activity relationship study.
Chemistry

Chemistry

Chemical Sciences Journal

Author(s): Karki R, Thapa P, Yoo HY, Kadayat TM, Park PH,

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Abstract Twelve dihydroxylated 2,4,6-triphenyl pyridines were designed and synthesized which contain hydroxyl groups at ortho, meta or para position of 2- and 6-phenyl, or 2- and 4-phenyl rings attached to the central pyridine. They were evaluated for topoisomerase I and II inhibitory activity, and cytotoxicity against several human cancer cell lines for the development of novel anticancer agents. Generally, dihydroxylated 2,4,6-triphenyl pyridines exhibited stronger topoisomerase II inhibitory activity, and cytotoxicity compared to those of monohydroxylated 2,4,6-triphenyl pyridines. The concrete structure-activity relationship was observed that dihydroxylated 2,4,6-triphenyl pyridines with hydroxyl group at meta or para position of 2-phenyl ring displayed significant topoisomerase II inhibitory activity as well as cytotoxicity. Positive correlation between topoisomerase II inhibitory activity and cytotoxicity was observed for compounds 10, 12, 13, 17-20 and 22. Copyright © 2012 Elsevier Masson SAS. All rights reserved. This article was published in Eur J Med Chem and referenced in Chemical Sciences Journal

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