TY - JOUR
T1 - Design, Synthesis, and Cytotoxicity and Topoisomerase I/IIα Inhibition Activity of Pyrazolo[4,3-f]quinoline Derivatives
AU - Chaudhary, Chhabi Lal
AU - Ko, Seungyun
AU - Lee, Chaerim
AU - Kim, Yerin
AU - Jung, Chanhyun
AU - Hyun, Soonsil
AU - Kwon, Youngjoo
AU - Kang, Jong Soon
AU - Jung, Jae Kyung
AU - Lee, Heesoon
N1 - 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.
PY - 2022/4
Y1 - 2022/4
N2 - 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.
AB - 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.
KW - anticancer agents
KW - cytotoxic effect
KW - human topoisomerase I and IIα inhibitors
KW - imino Diels–Alder reaction
KW - pyrazolo[4,3-f]quinoline derivatives
UR - http://www.scopus.com/inward/record.url?scp=85127711329&partnerID=8YFLogxK
U2 - 10.3390/ph15040399
DO - 10.3390/ph15040399
M3 - Article
AN - SCOPUS:85127711329
SN - 1424-8247
VL - 15
JO - Pharmaceuticals
JF - Pharmaceuticals
IS - 4
M1 - 399
ER -