Design, Synthesis, and Cytotoxicity and Topoisomerase I/IIα Inhibition Activity of Pyrazolo[4,3-f]quinoline Derivatives

Chhabi Lal Chaudhary, Seungyun Ko, Chaerim Lee, Yerin Kim, Chanhyun Jung, Soonsil Hyun, Youngjoo Kwon, Jong Soon Kang, Jae Kyung Jung, Heesoon Lee

Research output: Contribution to journalArticlepeer-review

3 Scopus citations


With the several targets of cancer treatment, inhibition of DNA topoisomerase activity is one of the well-known focuses in cancer chemotherapy. Here, we describe the design and synthesis of a novel series of pyrazolo[4,3-f]quinolines with potential anticancer/topoisomerase inhibition activity. Forty newly designed pyrazolo[4,3-f]quinoline derivatives were synthesized via inverse imino Diels–Alder reaction. The antiproliferative activity of the synthesized derivatives was initially measured in the human NUGC-3 cancer cell line. Then, the selected compounds 1B, 1C, 1M, 2A, 2D, 2E, 2F, and 2R with higher activity among tested compounds were screened against six cancer cell lines, including ACHN, HCT-15, MM231, NCI-H23, NUGC-3, and PC-3. The results demonstrated that the compounds 1M, 2E, and 2P were most effective in all cancer cell lines exhibiting GI50 below 8 µM. Among them, 2E showed an equivalent inhibition pattern of topoisomerase IIα activity to that of etoposide, positive control at a 100 µM dose.

Original languageEnglish
Article number399
Issue number4
StatePublished - Apr 2022

Bibliographical note

Funding Information:
Funding: This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIT) (NRF-2019R1F1A1057601) and the Medical Research Center Program (2017R1A5A2015541).

Publisher Copyright:
© 2022 by the authors. Licensee MDPI, Basel, Switzerland.


  • anticancer agents
  • cytotoxic effect
  • human topoisomerase I and IIα inhibitors
  • imino Diels–Alder reaction
  • pyrazolo[4,3-f]quinoline derivatives


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