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
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