Citation: ZHANG Huili, LI Ke, HUANG Wenlong, WANG Rui, HU Guoqiang. Synthesis and Antitumor Activity of N-Arylidene-Rhodanine Levofloxacin Amides[J]. Chinese Journal of Applied Chemistry, ;2019, 36(8): 897-903. doi: 10.11944/j.issn.1000-0518.2019.08.180409 shu

Synthesis and Antitumor Activity of N-Arylidene-Rhodanine Levofloxacin Amides

ZHANG Huili ^a ,
LI Ke ^a ,
HUANG Wenlong ^c ,
WANG Rui ^b,, ,
HU Guoqiang ^b,,

a.
The Institute of Applied Pharmacy, Zhengzhou University of Industrial Technology, Zhengzhou 451150, China
b.
College of Pharmacy, Henan University, Kaifeng, Henan 475001, China
c.
Center of Drug Discovery, China Pharmaceutical University, Nanjing 210009, China

Corresponding author: WANG Rui, lantsing@163.com HU Guoqiang, hgqxy@sina.com
Received Date: 24 December 2018
Revised Date: 19 March 2019
Accepted Date: 19 April 2019

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

Figures(1)

To develope an efficiently structural modification strategy for transforming antibacterial fluoroquinolone into antitumor agent, novel N-arylidene arylidene rhodanine levofloxacin amide derivatives(6a-6n) were synthesized via amide modification with functionalized arylidene rhodanine scaffold as the bioisostere of the C-3 carboxylic group. The in vitro antitumor assay indicated that the title compounds exhibited more significant potency against three test cancer cell lines than levofloxacin, but with lower cytotoxicity against the normal cells than doxorubicin as a comparison. The SAR(structure-activity relationship) reveals that the increase in the bulky or electron-donating substituents bearing phenyl ring obviously reduces the antitumor activity. Conversely, compounds with electron-withdrawing nitro-or fluorophenyl or heteroaromatic rings such as furan or pyridine ring display comparable activity to doxorubicin. Thus, an amide group modified by arylidene rhodanine scaffold as an isostere of the C-3 carboxylic acid group appears to an alternative route for further design of antitumor fluoroquinolone.
- fluoroquinolone,
- amide,
- rhodanine,
- α, β-unsaturated ketone,
- bioisostere,
- antitumor activity
1. [1]
  Mendgen T, Steuer C, Klein C D. Privileged Scaffolds or Promiscuous Binders:A Comparative Study on Rhodanines and Related Heterocycles in Medicinal Chemistry[J]. J Med Chem, 2012,55(2):743-753. doi: 10.1021/jm201243p
2. [2]
  Xiang Y, Chen C, Wang W M. Rhodanine as a Potent Scaffold for the Development of Broad-Spectrum Metallo-β-lactamase Inhibitors[J]. ACS Med Chem Lett, 2018,9(4):359-364. doi: 10.1021/acsmedchemlett.7b00548
3. [3]
  Slepikas L, Chiriano G, Perozzo R. In Silico Driven Design and Synthesis of Rhodanine Derivatives as Novel Antibacterials Targeting the Enoyl Reductase InhA[J]. J Med Chem, 2016,59(24):10917-10928. doi: 10.1021/acs.jmedchem.5b01620
4. [4]
  Zdrazil B, Guha R. The Rise and Fall of a Scaffold:A Trend Analysis of Scaffolds in the Medicinal Chemistry Literature[J]. J Med Chem, 2018,61(11):4688-4703. doi: 10.1021/acs.jmedchem.7b00954
5. [5]
  Jackson P A, Widen J C, Harki D A. Covalent Modifiers:A Chemical Perspective on the Reactivity of α, β-Unsaturated Carbonyls with Thiols via Hetero-Michael Addition Reactions[J]. J Med Chem, 2017,60(3):839-885. doi: 10.1021/acs.jmedchem.6b00788
6. [6]
  Bisacchi G S, Hale M R. A "Double-Edged" Scaffold:Antitumor Power Within the Antibacterial Quinolone[J]. Curr Med Chem, 2016,23(6):520-577. doi: 10.2174/0929867323666151223095839
7. [7]
  XIE Yusuo, GAO Liuzhou, YAN Qiang. Synthesis and Antitumor Activity of Fluoroquinolon-3-yl s-Triazole Sulfide-Ketone Thiosemicarbazone Derivatives of Ofloxacin[J]. Chinese J Appl Chem, 2016,33(1):25-31.
8. [8]
  LI Yuanyuan, ZHANG Chenxia, HUANG Wenlong. Synthesis and Antitumor Activity of C-3 Thiazolotriazole Unsaturated Ketone Derivatives from Levofloxacoin[J]. Chinese J Appl Chem, 2019,36(6):671-676.
9. [9]
  Hu G Q, Wang G Q, Duan N N. Design, Synthesis and Antitumor Activity of Fluoroquinolone C3 Heterocyclic Bis-oxadiazole Methylsulfide Derivatives Derived from Levofloxacin[J]. Chem Res Chinese Univ, 2012,28(6):980-984.
10. [10]
  GAO Liuzhou. Synthesis and Anti-proliferative Activity of Fluoroquinolone C3(Rhodanine Unsaturated Ketone) Amine Derivatives[D]. Kaifeng: School of Pharmacy, Henan University, 2015(in Chnese).
1. [1]
  Jing WU , Puzhen HUI , Huilin ZHENG , Pingchuan YUAN , Chunfei WANG , Hui WANG , Xiaoxia GU . Synthesis, crystal structures, and antitumor activities of transition metal complexes incorporating a naphthol-aldehyde Schiff base ligand. Chinese Journal of Inorganic Chemistry, 2024, 40(12): 2422-2428. doi: 10.11862/CJIC.20240278
2. [2]
  Chi Li , Jichao Wan , Qiyu Long , Hui Lv , Ying Xiong . N-Heterocyclic Carbene (NHC)-Catalyzed Amidation of Aldehydes with Nitroso Compounds. University Chemistry, 2024, 39(5): 388-395. doi: 10.3866/PKU.DXHX202312016
3. [3]
  Yue Zhao , Yanfei Li , Tao Xiong . Copper Hydride-Catalyzed Nucleophilic Additions of Unsaturated Hydrocarbons to Aldehydes and Ketones. University Chemistry, 2024, 39(4): 280-285. doi: 10.3866/PKU.DXHX202309001
4. [4]
  Ping Song , Nan Zhang , Jie Wang , Rui Yan , Zhiqiang Wang , Yingxue Jin . Experimental Teaching Design on Synthesis and Antitumor Activity Study of Cu-Pyropheophorbide-a Methyl Ester. University Chemistry, 2024, 39(6): 278-286. doi: 10.3866/PKU.DXHX202310087
5. [5]
  Yonghui ZHOU , Rujun HUANG , Dongchao YAO , Aiwei ZHANG , Yuhang SUN , Zhujun CHEN , Baisong ZHU , Youxuan ZHENG . Synthesis and photoelectric properties of fluorescence materials with electron donor-acceptor structures based on quinoxaline and pyridinopyrazine, carbazole, and diphenylamine derivatives. Chinese Journal of Inorganic Chemistry, 2024, 40(4): 701-712. doi: 10.11862/CJIC.20230373
6. [6]
  Lihui Jiang , Wanrong Dong , Hua Yang , Yongqing Xia , Hongjian Peng , Jun Yuan , Xiaoqian Hu , Zihan Zeng , Yingping Zou , Yiming Luo . Study on Extraction of p-Hydroxyacetophenone. University Chemistry, 2024, 39(11): 259-268. doi: 10.12461/PKU.DXHX202402056
7. [7]
  Lijuan Liu , Xionglei Wang . Preparation of Hydrogels from Waste Thermosetting Unsaturated Polyester Resin by Controllable Catalytic Degradation: A Comprehensive Chemical Experiment. University Chemistry, 2024, 39(11): 313-318. doi: 10.12461/PKU.DXHX202403060
8. [8]
  Hao Wu , Zhen Liu , Dachang Bai . ¹H NMR Spectrum of Amide Compounds. University Chemistry, 2024, 39(3): 231-238. doi: 10.3866/PKU.DXHX202309020
9. [9]
  Liangzhen Hu , Li Ni , Ziyi Liu , Xiaohui Zhang , Bo Qin , Yan Xiong . A Green Chemistry Experiment on Electrochemical Synthesis of Benzophenone. University Chemistry, 2024, 39(6): 350-356. doi: 10.3866/PKU.DXHX202312001
10. [10]
  Guojie Xu , Fang Yu , Yunxia Wang , Meng Sun . Introduction to Metal-Catalyzed β-Carbon Elimination Reaction of Cyclopropenones. University Chemistry, 2024, 39(8): 169-173. doi: 10.3866/PKU.DXHX202401060
11. [11]
  Yongqing Kuang , Jie Liu , Jianjun Feng , Wen Yang , Shuanglian Cai , Ling Shi . Experimental Design for the Two-Step Synthesis of Paracetamol from 4-Hydroxyacetophenone. University Chemistry, 2024, 39(8): 331-337. doi: 10.12461/PKU.DXHX202403012
12. [12]
  Meijin Li , Xirong Fu , Xue Zheng , Yuhan Liu , Bao Li . The Marvel of NAD⁺: Nicotinamide Adenine Dinucleotide. University Chemistry, 2024, 39(9): 35-39. doi: 10.12461/PKU.DXHX202401027
13. [13]
  Hong Zheng , Xin Peng , Chunwang Yi . The Tale of Caprolactam Cyclic Oligomers: The Ever-changing Life of “Princess Cyclo”. University Chemistry, 2024, 39(9): 40-47. doi: 10.12461/PKU.DXHX202403058
14. [14]
  Yuena Yu , Fang Fang . Microwave-Assisted Synthesis of Safinamide Methanesulfonate. University Chemistry, 2024, 39(11): 210-216. doi: 10.3866/PKU.DXHX202401076
15. [15]
  Xinghai Li , Zhisen Wu , Lijing Zhang , Shengyang Tao . Machine Learning Enables the Prediction of Amide Bond Synthesis Based on Small Datasets. Acta Physico-Chimica Sinica, 2025, 41(2): 100010-. doi: 10.3866/PKU.WHXB202309041
16. [16]
  Yurong Tang , Yunren Shi , Yi Xu , Bo Qin , Yanqin Xu , Yunfei Cai . Innovative Experiment and Course Transformation Practice of Visible-Light-Mediated Photocatalytic Synthesis of Isoquinolinone. University Chemistry, 2024, 39(5): 296-306. doi: 10.3866/PKU.DXHX202311087
17. [17]
  Zhuoming Liang , Ming Chen , Zhiwen Zheng , Kai Chen . Multidimensional Studies on Ketone-Enol Tautomerism of 1,3-Diketones By ¹H NMR. University Chemistry, 2024, 39(7): 361-367. doi: 10.3866/PKU.DXHX202311029
18. [18]
  Qiqi Li , Su Zhang , Yuting Jiang , Linna Zhu , Nannan Guo , Jing Zhang , Yutong Li , Tong Wei , Zhuangjun Fan . 前驱体机械压实制备高密度活性炭及其致密电容储能性能. Acta Physico-Chimica Sinica, 2025, 41(3): 2406009-. doi: 10.3866/PKU.WHXB202406009
19. [19]
  Shiyi WANG , Chaolong CHEN , Xiangjian KONG , Lansun ZHENG , Lasheng LONG . Polynuclear lanthanide compound [Ce₄^ⅢCe₆^Ⅳ(μ₃-O)₄(μ₄-O)₄(acac)₁₄(CH₃O)₆]·2CH₃OH for the hydroboration of amides to amine. Chinese Journal of Inorganic Chemistry, 2025, 41(1): 88-96. doi: 10.11862/CJIC.20240342
20. [20]
  Mei Yan , Rida Feng , Yerdos·Tohtarkhan , Biao Long , Li Zhou , Chongshen Guo . Expansion and Extension of Liquid Saturated Vapor Measurement Experiment. University Chemistry, 2024, 39(3): 294-301. doi: 10.3866/PKU.DXHX202308103

Get Citation

PDF

XML

Metrics

PDF Downloads(4)
Abstract views(950)
HTML views(153)

通讯作者: 陈斌, bchen63@163.com

1.
沈阳化工大学材料科学与工程学院沈阳 110142