Synthesis and SAR study of new hydroxy and chloro-substituted 2,4-diphenyl 5H-chromeno[4,3-b]pyridines as selective topoisomerase IIα-targeting anticancer agents

Til Bahadur Thapa Magar, Seung Hee Seo, Tara Man Kadayat, Hyunji Jo, Aarajana Shrestha, Ganesh Bist, Pramila Katila, Youngjoo Kwon, Eung Seok Lee

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10 Scopus citations

Abstract

As part of our effort to develop potential topoisomerase IIα (topo IIα) targeting anticancer agents, we systematically designed a new series of hydroxy and chloro-substituted 2,4-diphenyl 5H-chromeno[4,3-b]pyridines. Total eighteen compounds were synthesized and tested for their ability to inhibit the function of topo I and IIα and proliferation of human breast (T47D), colorectal (HCT15), and cervix (HeLa) cancer cells. Except compound 11, all of the tested compounds displayed selective topo IIα inhibitory activity. Compounds 8–18, 22, 24, and 25 showed excellent topo IIα inhibitory activity than a positive control, etoposide. Most of the compounds appeared to be superior to reference compounds in their antiproliferative activity. Structure-activity relationship (SAR) study has shown that it is better to place the hydroxyphenyl group at the 4-position of the central pyridine for superior topo IIα inhibition and antiproliferative activity. Similarly, the 3′-, or 4′-hydroxyphenyl substitution at the 2- and 4-positon of pyridine ring is important for better activity than 2′-substitution.

Original languageEnglish
Pages (from-to)1909-1919
Number of pages11
JournalBioorganic and Medicinal Chemistry
Volume26
Issue number8
DOIs
StatePublished - 1 May 2018

Keywords

  • 5H-Chromeno[4,3-b]pyridines
  • Anticancer agents
  • Hydroxyl and chlorine-substitution
  • SAR study
  • Selective topoisomerase IIα inhibition

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