A new phenolic series of indenopyridinone as topoisomerase inhibitors: Design, synthesis, and structure-activity relationships

Aarajana Shrestha, Seojeong Park, Hae Jin Jang, Pramila Katila, Ritina Shrestha, Youngjoo Kwon, Eung Seok Lee

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

DNA Topoisomerase IIα (topo IIα) is one of the most effective therapeutic targets to control cancer. In an effort to develop novel and effective topo IIα targeting anti-proliferative agent, a phenolic series of indenopyridinone and indenopyridinol were designed and prepared using efficient multi-component one pot synthetic method. Total twenty-two synthesized compounds were assessed for topo I and IIα inhibition, and anti-proliferation in three different human cancer cell lines. Overall structure-activity relationship study explored the significance of meta-phenolic group at 4-position and para-phenolic group at 2- and/or 4-position of indenopyridinone skeleton for strong topo IIα-selective inhibition and anti-proliferative activity against human cervix (HeLa) and colorectal (HCT15) cell lines. Compound 12 with excellent topo IIα inhibition (93.7%) was confirmed as a DNA intercalator that could be a new promising lead to develop effective topo IIα-targeted anticancer agents.

Original languageEnglish
Pages (from-to)5212-5223
Number of pages12
JournalBioorganic and Medicinal Chemistry
Volume26
Issue number18
DOIs
StatePublished - 1 Oct 2018

Keywords

  • Anti-proliferative activity
  • DNA intercalator
  • Indenopyridinone
  • Phenolic group
  • Topoisomerase inhibitor

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