Citation: ZHANG Huili, CUI Hongyan, HUANG Wenlong, HU Guoqiang. Synthesis and Antitumor Activity of 3-Arylidene-Quinolin-4-Ones Derivatives of Levofloxacin[J]. Chinese Journal of Applied Chemistry, ;2020, 37(12): 1426-1431. doi: 10.11944/j.issn.1000-0518.2020.12.200177 shu

Synthesis and Antitumor Activity of 3-Arylidene-Quinolin-4-Ones Derivatives of Levofloxacin

a.
Henan Engineering Technology Research Center of Water Environment and Health, Zhengzhou University of industrial Technology, Zhengzhou 451150, China
b.
School of Clinical Medicine, Henan University, Kaifeng, He'nan 475001, China
c.
Center of Drug Discovery, China Pharmaceutical University, Nanjing 210009, China

Corresponding author: CUI Hongyan, lee7758521_1@163.com HU Guoqiang, hgqxy@sina.com
Received Date: 11 June 2020
Revised Date: 10 August 2020
Accepted Date: 18 September 2020

Fund Project: the National Natural Science Foundation of China 20872028the National Natural Science Foundation of China 21072045Supported by the National Natural Science Foundation of China(No.20872028, No.21072045) and the Science and Technology Development Plan Project of Henan Province(No.162102310392)the Science and Technology Development Plan Project of Henan Province 162102310392

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To further explore an efficient structural modification strategy, a fragment-based drug design, for improving the antitumor activity of fluoroquinolones, twelve novel 3-arylidene-quinolin-4(1H)-ones as levofloxacin derivatives (3a-3l) were synthesized by a condensation reaction of dihydroquinolin-4(1H)-one with aromatic aldehydes. The measured half inhibition concentration(IC₅₀) values using human hepatocellular carcinoma cell lines (SMMC-7721), human pancreatic cancer cell lines (Capan-1) and human leukemia cell line (HL60) cell lines reveal that the antitumor activities of the synthesized compounds are more potent than that of levofloxacin. Meanwhile, the halophenyl compounds such as fluorophenyl (3i, 3j), chlorophenyl (3k) or bromophenyl compounds (3l) display better activities than the control compounds, especially the IC₅₀ value of chlorophenyl (3k) against SMMC-7721 and Capan-1 cell is comparable to that of doxorubicin. Thus, 3-arylidene-quinolin-4(1H)-one skeleton instead of quinolin-4(1H)-one-3-carboxylic acid is beneficial to improve the antitumor activities of fluoroquinolones. Furthermore, an α, β-unsaturated ketone fragment as a promising candidate pharmacophore for an alternative modified group of fluoroquinolone needs to be developed.
- topoisomerase,
- fluoroquinolone,
- quinoline,
- α, β-unsaturated ketone,
- antitumor activity
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