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

doi:10.11944/j.issn.1000-0518.2020.12.200177

Chinese Journal of Applied Chemistry ›› 2020, Vol. 37 ›› Issue (12): 1426-1431.DOI: 10.11944/j.issn.1000-0518.2020.12.200177

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

ZHANG Huili^a, CUI Hongyan^b*, HUANG Wenlong^c, HU Guoqiang^b*

^aHenan Engineering Technology Research Center of Water Environment and Health, Zhengzhou University of industrial Technology,Zhengzhou 451150,China;
^bSchool of Clinical Medicine,Henan University,Kaifeng,He'nan 475001,China;
^cCenter of Drug Discovery,China Pharmaceutical University,Nanjing 210009,China

Received:2020-06-11 Revised:2020-08-10 Accepted:2020-09-18 Published:2020-12-01 Online:2020-12-07
Contact: HU Guoqiang, professor; Tel/Fax:0371-223880680; E-mail:hgqxy@sina.com; Research interests:drug molecular design
Co-corresponding author:CUI Hongyan, experimentalist; Tel/Fax:0371-22387178; E-mail:lee7758521_1@163.com; Research interests:pharmacology
Supported by:
National Natural Science Foundation of China(No.20872028, No.21072045) and the Science and Technology Development Plan Project of Henan Province(No.162102310392)

Abstract

Abstract: 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 IC₅₀value 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.

Key words: topoisomerase, fluoroquinolone, quinoline, α,β-unsaturated ketone, antitumor activity

CLC Number:

O626.2

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.

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

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