Design, synthesis and biological evaluation of 1,3-diphenylbenzo[f][1,7]naphthyrdines

Sateesh Kumar Arepalli, Byeongwoo Park, Kiho Lee, Hyunji Jo, Kyu Yeon Jun, Youngjoo Kwon, Jong Soon Kang, Jae Kyung Jung, Heesoon Lee

Research output: Contribution to journalArticlepeer-review

9 Scopus citations


A novel series of twenty 1,3-diphenylbenzo[f][1,7]benzonaphthyrdine derivatives were designed and synthesized through intermolecular imino Diels-Alder reaction. Their in vitro cytotoxic activities were evaluated against six human cancer cell lines (NCIH23, HCT15, NUGC-3, ACHN, PC-3, and MDA-MB-231). Majority of synthesized compounds exhibited significant cytotoxic activities against all tested human cancer cell lines. Among them 4l, 4m, and 4o derivatives exhibited most promising cytotoxic activities. Furthermore these compounds were evaluated against human Topoisomerase IIα inhibition. Interestingly, the compound 4l exhibited 1.3 and 1.2 times more potent human Topoisomerase IIα inhibition than the reference drug etoposide in both 100 µM and 20 µM concentrations respectively. Molecular docking studies for the compound 4l have also been executed by Sybyl X-2.1 in which it reveals the binding site of the compound 4l with topo IIα DNA cleavage site where etoposide was situated. The benzo[f][1,7]naphthyridine ring was stacked between the DNA bases of the cleavage site.

Original languageEnglish
Pages (from-to)5586-5597
Number of pages12
JournalBioorganic and Medicinal Chemistry
Issue number20
StatePublished - 2017

Bibliographical note

Funding Information:
This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (NRF- 2015R1D1A1A01058142 ), Korea Research Fellowship Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT and Future Planning (NRF- 2016H1D3A1937140 ) and Medical Research Center Program ( 2017R1A5A2015541 ).

Publisher Copyright:
© 2017 Elsevier Ltd


  • 1,3-Diphenylbenzo[f][1,7]benzonaphthyrdines
  • Cytotoxic agents
  • Human Topoisomerase IIα inhibitors
  • Imino Diels-Alder reaction
  • Molecular docking studies


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