Citation: XIE Yusuo, GAO Liuzgou, YAN Qiang, WU Shumin, NI Lili, LIU Yingjie, HUANG Wenlong, HU Guoqiang. Synthesis and Antitumor Activity of Fluoroquinolon-3-yl s-Triazole Sulfide-ketone Thiosemicarbazone Derivatives of Ofloxacin[J]. Chinese Journal of Applied Chemistry, ;2016, 33(1): 25-31. doi: 10.11944/j.issn.1000-0518.2016.01.150182 shu

Synthesis and Antitumor Activity of Fluoroquinolon-3-yl s-Triazole Sulfide-ketone Thiosemicarbazone Derivatives of Ofloxacin

XIE Yusuo ^a ,
GAO Liuzgou ^a ,
YAN Qiang ^a ,
WU Shumin ^a ,
NI Lili ^a ,
LIU Yingjie ^c,, ,
HUANG Wenlong ^b ,
HU Guoqiang ^a,,

1.
a Institute of Chemical Biology, He'nan University, Kaifeng, He'nan 475001, China;
2.
b Centre of Drug Discovery, China Pharmaceutical University, Nanjing 210009, China;
3.
c Department of Microbiology, Medical College He'nan University, Kaifeng, He'nan 475001, China

Corresponding author: LIU Yingjie, HU Guoqiang,
Received Date: 26 May 2015
Available Online: 8 October 2015
Fund Project:

To discover efficient structural modification strategy for the conversion of antibacterial activity of fluoroquinolones into antitumor activity, an azole heterocycle modified with sulfide-ketone thiosemicarbazone chain was designed as the bioisosteric replacement of the C-3 carboxylic acid group. Consequently, novel s-triazole-based thiosemicarbazone derivatives(6a~6g) were synthesized from ofloxacin 1, respectively. The structures of the title compounds(6a~6g) were characterized by elemental analysis and spectral data, and the in vitro antitumor activity was also evaluated by the MTT assay. Compounds(6a~6g) exhibit more significantly antiproliferative activity than both of parent ofloxacin 1 and the corresponding sulfide-ketone intermediates(5a~5g). These thiosemicarbazones, particularly those containing nitro group or fluorine atom, have comparable activity to doxorubicin. Therefore, it suggests that an azole ring modified with functional side-chain as the bioisosteric replacement of the C-3 carboxylic group is favorable for an improvement of antitumor activity of fluoroquinolones.
- fluoroquinolone,
- bioisosterism,
- s-triazole,
- sulfide,
- thiosemicarbazone,
- antitumor activity
1. [1]
  [1] Pirhadi S,Shiri F,Ghasemi J B.Methods and Applications of Structure-based Pharmacophores in Drug Discovery[J].Curr Top Med Chem,2013,13(9):1036-1047.
2. [2]
  [2] GUO Zongru.Strategy of Molecular Drug Design:Activity and Druggability[J].Acta Pharm Sin,2010,45(5):539-547(in Chinese).郭宗儒.药物分子设计与策略:药理活性与成药性[J].药学学报,2010,45(5):539-547.
3. [3]
  [3] Suresh N,Nagesh HN,Sekhar KV,et al.Synthesis of Novel Ciprofloxacin Analogues and Evaluation of Their Anti-proliferative Effect on Human Cancer Cell Lines[J].Bioorg Med Chem Lett,2013,23(23):6292-6295.
4. [4]
  [4] WANG Guoqiang,DUAN Nannan,CAO Tieyao,et al.Antitumor Fluoroquinolone C3-Isostere Derivatives (Ⅰ)-Synthesis and Activity of Bis-oxadiazole Methyl-sulfide Derivatives[J].Chinese J Appl Chem,2012,29(7):769-774(in Chinese).王国强,段楠楠,曹铁耀,等.抗肿瘤氟喹诺酮C3等排衍生物(Ⅰ)-双噁二唑甲硫醚衍生物的合成和抗肿瘤活性[J].应用化学,2012,29(7):769-774.
5. [5]
  [5] XIE Songqiang,CHEN Yinsheng,WANG Guoqiang,et al.Part Ⅳ.Synthesis and Antitumor Evaluation of s-Triazolothiadiazines and Pyrazolo s-Triazoles Derived From Ciproxacin[J].Acta Pharm Sin,2012,47(1):66-71(in Chinese).谢松强,陈寅生,王国强,等.Part Ⅳ.环丙沙星C-3羧基衍生物均三唑并噻二嗪及吡唑并均三唑的合成和抗肿瘤活性研究[J].药学学报,2012,47(1):66-71.
6. [6]
  [6] Megally Abdo N Y,Kamel M M.Synthesis and Anticancer Evaluation of 1,3,4-Oxadiazoles,1,3,4-Thiadiazoles,1,2,4-Triazoles and Mannich Bases[J].Chem Pharm Bull(Tokyo),2015,63(5):369-376.
7. [7]
  [7] Huang H,Chen Q,Ku X,et al.A Series of Alpha-heterocyclic Carboxaldehyde Thiosemicarbazones Inhibit Topoisomerase Ⅱ Alpha Catalytic Activity[J].J Med Chem,2010,53(8):3048-3064.
8. [8]
  [8] XU Qiuju,Hou Lili,WU Zhaofeng,et al.Synthesis and Antitumor Evaluation of Fluoroquinolon C3s-Triazole Oxadiazole Methylsulfide Derivatives of Ofloxacin[J].Chinese Pharm J,2014,49(7):609-612(in Chinese).许秋菊,侯莉莉,仵钊锋,等.氟喹诺酮C3均三唑噁二唑甲硫醚衍生物的合成及抗肿瘤活性[J].中国药学杂志,2014,49(7):609-612.
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]
  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
3. [3]
  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
4. [4]
  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
5. [5]
  Tianlong Zhang , Rongling Zhang , Hongsheng Tang , Yan Li , Hua Li . Online Monitoring and Mechanistic Analysis of 3,5-diamino-1,2,4-triazole (DAT) Synthesis via Raman Spectroscopy: A Recommendation for a Comprehensive Instrumental Analysis Experiment. University Chemistry, 2024, 39(6): 303-311. doi: 10.3866/PKU.DXHX202312006
6. [6]
  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
7. [7]
  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
8. [8]
  Jian Li , Yu Zhang , Rongrong Yan , Kaiyuan Sun , Xiaoqing Liu , Zishang Liang , Yinan Jiao , Hui Bu , Xin Chen , Jinjin Zhao , Jianlin Shi . 高效靶向示踪钙钛矿纳米系统光电增效抗肿瘤. Acta Physico-Chimica Sinica, 2025, 41(5): 100042-. doi: 10.1016/j.actphy.2024.100042
9. [9]
  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
10. [10]
  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
11. [11]
  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
12. [12]
  Shahua Huang , Xiaoming Guo , Lin Lin , Guangping Chang , Sheng Han , Zuxin Zhou . Application of “Integration of Industry and Education” in Engineering Chemistry: Improvement of the Pesticide Fipronil Production. University Chemistry, 2024, 39(3): 199-204. doi: 10.3866/PKU.DXHX202309064
13. [13]
  Ruiqing LIU , Wenxiu LIU , Kun XIE , Yiran LIU , Hui CHENG , Xiaoyu WANG , Chenxu TIAN , Xiujing LIN , Xiaomiao FENG . Three-dimensional porous titanium nitride as a highly efficient sulfur host. Chinese Journal of Inorganic Chemistry, 2024, 40(5): 867-876. doi: 10.11862/CJIC.20230441
14. [14]
  Aidang Lu , Yunting Liu , Yanjun Jiang . Comprehensive Organic Chemistry Experiment: Synthesis and Characterization of Triazolopyrimidine Compounds. University Chemistry, 2024, 39(8): 241-246. doi: 10.3866/PKU.DXHX202401029
15. [15]
  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
16. [16]
  Hong CAI , Jiewen WU , Jingyun LI , Lixian CHEN , Siqi XIAO , Dan LI . Synthesis of a zinc-cobalt bimetallic adenine metal-organic framework for the recognition of sulfur-containing amino acids. Chinese Journal of Inorganic Chemistry, 2025, 41(1): 114-122. doi: 10.11862/CJIC.20240382
17. [17]
  Changqing MIAO , Fengjiao CHEN , Wenyu LI , Shujie WEI , Yuqing YAO , Keyi WANG , Ni WANG , Xiaoyan XIN , Ming FANG . Crystal structures, DNA action, and antibacterial activities of three tetranuclear lanthanide-based complexes. Chinese Journal of Inorganic Chemistry, 2024, 40(12): 2455-2465. doi: 10.11862/CJIC.20240192
18. [18]
  Ruiying WANG , Hui WANG , Fenglan CHAI , Zhinan ZUO , Benlai WU . Three-dimensional homochiral Eu(Ⅲ) coordination polymer and its amino acid configuration recognition. Chinese Journal of Inorganic Chemistry, 2025, 41(5): 877-884. doi: 10.11862/CJIC.20250052
19. [19]
  Haitang WANG , Yanni LING , Xiaqing MA , Yuxin CHEN , Rui ZHANG , Keyi WANG , Ying ZHANG , Wenmin WANG . Construction, crystal structures, and biological activities of two Ln^Ⅲ₃ complexes. Chinese Journal of Inorganic Chemistry, 2024, 40(8): 1474-1482. doi: 10.11862/CJIC.20240188
20. [20]
  Linjie ZHU , Xufeng LIU . Synthesis, characterization and electrocatalytic hydrogen evolution of two di-iron complexes containing a phosphine ligand with a pendant amine. Chinese Journal of Inorganic Chemistry, 2025, 41(5): 939-947. doi: 10.11862/CJIC.20240416

Get Citation

PDF

XML

Metrics

PDF Downloads(1)
Abstract views(375)
HTML views(39)

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