Synthesis, antitumor activity, and structure-activity relationship study of trihydroxylated 2,4,6-triphenyl pyridines as potent and selective topoisomerase II inhibitors

Radha Karki, Chanmi Park, Kyu Yeon Jun, Jun Goo Jee, Jun Ho Lee, Pritam Thapa, Tara Man Kadayat, Youngjoo Kwon, Eung Seok Lee

Research output: Contribution to journalArticlepeer-review

32 Scopus citations

Abstract

A series of eighteen trihydroxylated 2,4,6-triphenyl pyridines were designed and synthesized which contain hydroxyl groups at ortho, meta or para position of each 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. Most of the compounds exhibited strong and selective topoisomerase II inhibitory activity compared to the positive control, etoposide, and also displayed significant cytotoxicity in low micromolar range. Trihydroxylated 2,4,6-triphenyl pyridines were more potent than mono- and di-hydroxylated 2,4,6-triphenyl pyridines, which have been previously studied in our research group. Positive correlation between topoisomerase II inhibitory activity and cytotoxicity was observed for the most compounds. Molecular docking study shows qualitatively consistent with the results of biological assays.

Original languageEnglish
Pages (from-to)555-565
Number of pages11
JournalEuropean Journal of Medicinal Chemistry
Volume84
DOIs
StatePublished - 12 Sep 2014

Keywords

  • Anticancer agents
  • Cytotoxicity
  • Docking study
  • Topo II inhibitory activity
  • Topoisomerase I
  • Topoisomerase II
  • Trihydroxylated 2,4,6-triphenyl pyridines

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