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

doi:10.11944/j.issn.1000-0518.2016.01.150182

Chinese Journal of Applied Chemistry ›› 2016, Vol. 33 ›› Issue (1): 25-31.DOI: 10.11944/j.issn.1000-0518.2016.01.150182

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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^*()

^aInstitute of Chemical Biology,He'nan University,Kaifeng,He'nan 475001,China
^bCentre of Drug Discovery,China Pharmaceutical University,Nanjing 210009,China
^cDepartment of Microbiology,Medical College He'nan University,Kaifeng,He'nan 475001,China

Received:2015-05-26 Accepted:2015-10-08 Published:2016-01-05 Online:2016-01-05
Contact: LIU Yingjie,HU Guoqiang
Supported by:
Supported by the National Natural Science Foundation of China(No.21072045, No.20872028)

Abstract

Abstract:

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.

Key words: fluoroquinolone, bioisosterism, s-triazole, sulfide, thiosemicarbazone, antitumor activity

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.

References

[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]	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]	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]	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]	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]	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]	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]	XU Qiuju,Hou Lili,WU Zhaofeng,et al.Synthesis and Antitumor Evaluation of Fluoroquinolon C3 s-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.

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

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