Synthesis and biological evaluation of 2-phenol-4-chlorophenyl-6-aryl pyridines as topoisomerase II inhibitors and cytotoxic agents

Pritam Thapa, Tara Man Kadayat, Seojeong Park, Somin Shin, Til Bahadur Thapa Magar, Ganesh Bist, Aarajana Shrestha, Younghwa Na, Youngjoo Kwon, Eung Seok Lee

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

A new series of 2-phenol-4-chlorophenyl-6-aryl pyridines were designed, synthesized, and evaluated for topoisomerase (topo) I and II inhibitory activities as well as cytotoxic activity against four different human cancer cell lines such as HCT15, T47D, DU145, and Hela. Most of the tested compounds exhibited stronger topo II inhibitory activity at 100 μM as compared to etoposide. All the compounds, except 39, did not show topo I inhibitory activity. Interestingly, compounds that showed better topo II inhibition than etoposide have ortho- or para-chlorophenyl at 4-position of central pyridine, and none of the compounds possess meta-chlorophenyl. SAR study revealed the importance of ortho- or para-chlorophenyl at 4-position of the central pyridine for selective topo II inhibitory activity. Similarly, all compounds possessing meta- or para-hydroxyphenyl moieties showed moderate to significant cytotoxic effects. Particularly, compounds 27-37, and 39 which showed excellent cytotoxicity (IC50 = 0.68-1.25 μM) against T47D breast cancer cells suggest the importance of meta- or para-hydroxyphenyl moiety at 2-position of the central pyridine for the design of anticancer agents with related scaffolds.

Original languageEnglish
Pages (from-to)145-159
Number of pages15
JournalBioorganic Chemistry
Volume66
DOIs
StatePublished - Jun 2016

Keywords

  • 2-Phenol-4-chlorophenyl-6-aryl pyridines
  • Cytotoxicity
  • Synthesis
  • Topoisomerase I and II inhibition

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