Citation: Hui-Li ZHANG, Hong-Yan CUI, Wen-Long HUANG, Guo-Qiang HU. Synthesis and Antitumor Activity of Rhodanine Methylene-Substituted Levofloxacin Derivatives[J]. Chinese Journal of Applied Chemistry, ;2021, 38(2): 188-194. doi: 10.19894/j.issn.1000-0518.200199 shu

Synthesis and Antitumor Activity of Rhodanine Methylene-Substituted Levofloxacin Derivatives

1.
Henan Engineering Technology Research Center of Water Environment and Health, Zhengzhou University of Industrial Technology, Zhengzhou 451150, China
2.
School of Clinical Medicine, Henan University, Kaifeng 475001, China
3.
Center of Drug Discovery, China Pharmaceutical University, Nanjing 210009, China

Corresponding author: Hong-Yan CUI, lee7758521_1@163.com Guo-Qiang HU, hgqxy@sina.com.cn
Received Date: 28 June 2020
Accepted Date: 4 September 2020

Fund Project: the National Natural Science Foundation of China 20872028the National Natural Science Foundation of China 21072045

Figures(2)

To explore an efficient structural modification strategy to enhance the antitumor activity of fluoroquinolones, a methane-rhodanine fragment was used as the bioisosteric replacement of the C-3 carboxylic acid group and consequently twelve new C-3 α, β-unsaturated thiazolone derivatives (6a-6l) were designed and synthesized by Claisen-Schmid condensation reaction with oxazinoquinolin-7-one-6-carbaldehyde (5) derived from levofloxacin (1) and N-substituted rhodanines (2a-2l), respectively. The in vitro antitumor activity of the synthesized compounds is more potent than that of levofloxacin along with lower cytotoxicity against Vero cells. Meanwhile, the structure-activity relationship (SAR) reveals that halophenyl, N-unsubstituted or cyclopropyl rhodaninec ompounds display a better activity than those of the control compounds, especially the IC₅₀ values of cyclopropyl rhodanine compound (6j) against A549 cell growth is comparable to doxorubicin. Thus, an unsaturated ketone annulated rhodanine scaffold as a bioisostere of the C-3 carboxylic acid group is found to be an alternative proposal for improving the antitumor activity of fluoroquinolones. Furthermore, whether an α, β-unsaturated ketone fragment is a promising bioisostere of the C-3 carboxylic acid group is worth further developing.
- Fluoroquinolone,
- Rhodanine,
- Unsaturated ketone,
- Bioisostere,
- Antitumor activity
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