Citation: LI Yuanyuan, ZHANG Chengxia, HUANG Wenlong, CHEN Chaoran, HU Guoqiang. Synthesis and Antitumor Activities of C-3 Thiazolotriazole Unsaturated Ketone Derivatives of Levofloxacoin[J]. Chinese Journal of Applied Chemistry, ;2019, 36(6): 671-676. doi: 10.11944/j.issn.1000-0518.2019.06.180355 shu

Synthesis and Antitumor Activities of C-3 Thiazolotriazole Unsaturated Ketone Derivatives of Levofloxacoin

a.
Henan Vocational College of Applied Technology, Zhengzhou 450042, China
b.
Institute of Drugs, He'nan University, Zhengzhou 450042, China
c.
Center of Drug Discovery, China Pharmaceutical University, Nanjing 210009, China
d.
Institute of Nursing and Health, He'nan University, Kaifeng, He'nan 475001, China

Corresponding author: CHEN Chaoran, kfccr@126.com HU Guoqiang, hgqxy@sina.com
Received Date: 8 November 2018
Revised Date: 10 December 2018
Accepted Date: 17 January 2019

Fund Project: Supported by the National Natural Science Foundation of China(No.20872028, No.21072045), the He′nan Science and Technology Development Project(No.1621023039)the National Natural Science Foundation of China 21072045the He′nan Science and Technology Development Project 1621023039the National Natural Science Foundation of China 20872028

Figures(1)

To further develop an efficient structural modification strategy for the conversion of the antibacterial activity of fluoroquinolone into an antitumor activity, fused heterocyclic with unsaturated ketone was designed as the bioisosteric replacement of the C-3 carboxylic acid group. Accordingly, twelve novel C-3 thiazolotriazole unsaturated ketones(6a-6l) were synthesized from levofloxacin 1. The in vitro antitumor activity of the title compounds exhibited more significant potency than that of levofloxacin. The compounds with fluorophenyl or o-methoxyphenyl displayed comparable activity to doxorubicin. Thus, a fused heterocyclic unsaturated ketone skeleton as an isostere of the C-3 carboxylic acid group appears to be an alternative route for further design of lead antitumor fluoroquinolone.
- fluoroquinolone,
- s-triazole,
- thiazole,
- thiazolotriazole,
- α, β-unsaturated ketone,
- antitumor activity
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1.
沈阳化工大学材料科学与工程学院沈阳 110142