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Chinese Journal of Organic Chemistry >

2013 , Vol. 33 >Issue 11: 2384 - 2390

DOI: https://doi.org/10.6023/cjoc201306035

Articles

Design, Synthesis and Antitumor Study of Novel 1,4-Bispiperazine-carbodithioic Acid [1-Substituted-(1,2,3-triazole)-4]-methyl Esters

  • Wang Mengmeng ,
  • Duan Yingchao ,
  • Ye Xianwei ,
  • Ren Jingli ,
  • Yu Bin ,
  • Zhang En ,
  • Liu Hongmin
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  • School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001

Received date: 2013-06-21

  Revised date: 2013-07-07

  Online published: 2013-07-11

Supported by

Project supported by the National Natural Science Foundation of China (Nos. 81172937, U1204206), the New Teachers’ Fund for Doctor Stations, Ministry of Education (No. 20114101120013) and the National Science Foundation for Post-doctoral Scientists of China (Nos. 20100480857, 201104402).

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Abstract

In order to find novel lead compounds with promising antitumor activity, a series of novel 1, 4-bispiperazine-carbodithioic acid [1-substituted-(1, 2, 3-triazole)-4]-methyl esters were designed and synthesized. Commercially available pi-perazine reacting with CS2 and propargyl bromide in the presence of Na3PO4·12H2O in one pot gave compound 1, which was further reacted with appropriately substituted azide derivatives by click reaction to afford desired target compounds 3a～3o. The structures were characterized by 1H NMR, 13C NMR and HRMS. The compounds were evaluated for antitumor activity against four selected human tumor cell lines of EC-9706, MGC-803, SMMC-7721 and MCF-7. Several compounds exhibited moderate to potent activity. Particularly, compound 3a was more potent than 5-fluorouracil against MGC-803 and SMMC-7721 with IC50 values of 11.15 and 14.75 μmol/L.

Key words： 1,2,3-triazole; dithiocarbamate; click chemistry; antitumor activity

Cite this article

Wang Mengmeng , Duan Yingchao , Ye Xianwei , Ren Jingli , Yu Bin , Zhang En , Liu Hongmin . Design, Synthesis and Antitumor Study of Novel 1,4-Bispiperazine-carbodithioic Acid [1-Substituted-(1,2,3-triazole)-4]-methyl Esters[J]. Chinese Journal of Organic Chemistry, 2013 , 33(11) : 2384 -2390 . DOI: 10.6023/cjoc201306035

References

[1] Bock,V.D.; Speijer,D.; Hiemstra,H.; van Maarseveen,J.H.Org.Biomol.Chem.2007,5,971.
[2] Vatmurge,N.S.; Hazra,B.G.; Pore,V.S.; Shirazi,F.; Chavan,P.S.; Deshpande,M.V.Bioorg.Med.Chem.Lett.2008,18,2043.
[3] Whiting,M.; Muldoon,J.; Lin,Y.-C.; Silverman,S.M.; Lindstrom,W.; Olson,A.J.; Kolb,H.C.; Finn,M.G.; Sharpless,K.B.; Elder,J.H.; Fokin,V.V.Angew.Chem.,Int.Ed.2006,45,1435.
[4] Aher,N.G.; Pore,V.S.; Mishra,N.N.; Kumar,A.; Shukla,P.K.; Sharma,A.; Bhat,M.K.Bioorg.Med.Chem.Lett.2009,19,759.
[5] Buckle,D.R.; Outred,D.J.; Rockell,C.J.M.; Smith,H.; Spicer,B.A.J.Med.Chem.1983,26,251.
[6] Patpi,S.R.; Pulipati,L.; Yogeeswari,P.; Sriram,D.; Jain,N.; Sridhar,B.; Murthy,R.; T,A.D.; Kalivendi,S.V.; Kantevari,S.J.Med.Chem.2012,55,3911.
[7] Wang,X.-L.; Wan,K.; Zhou,C.-H.Eur.J.Med.Chem.2010,45,4631.
[8] Whiting,M.; Tripp,J.C.; Lin,Y.-C.; Lindstrom,W.; Olson,A.J.; Elder,J.H.; Sharpless,K.B.; Fokin,V.V.J.Med.Chem.2006,49,7697.
[9] Kolb,H.C.; Finn,M.G.; Sharpless,K.B.Angew.Chem.,Int.Ed.2001,40,2004.
[10] Fang,H.-B.; Jin,L.; Huang,N.-Y.; Wang,J.-Z.; Zou,K.; Luo,Z.-G.Chin.J.Chem.2013,31,831.
[11] Liu,J.-M.; Liu,M.-W.; Yue,Y.-Y.; Yao,M.-H.; Zhuo,K.-L.Chin.J.Chem.2012,30,644.
[12] Maryam,C.H.; Roghayeh,C.; Maryam,B.; Ghaffar,H.; Hamed,T.Chin.J.Chem.2012,30,223.
[13] He,W.-Y.; Si,H.-Z.; Luan,F.; Wu,L.-Y.; Zhou,J.-L.; He,M.-X.; Chen,G.-Y.Acta Chim.Sinica 2013,71,837 (in Chinese)(何文英,司宏宗,栾峰,吴禄勇,周纪龙,何明霞,陈光英,化学学报,2013,71,837.)
[14] Jin,P.-Y.; Lu,J.-R.; Zhao,C.-Y.; Ju,Y.Chin.J.Org.Chem.2012,32,1673 (in Chinese).(金培元,卢金荣,赵长琦,巨勇,有机化学,2012,32,1673.)
[15] Pagliai,F.; Pirali,T.; Del Grosso,E.; Di Brisco,R.; Tron,G.C.; Sorba,G.; Genazzani,A.A.J.Med.Chem.2005,49,467.
[16] Vantikommu,J.; Palle,S.; Surendra Reddy,P.; Ramanatham,V.; Khagga,M.; Pallapothula,V.R.Eur.J.Med.Chem.2010,45,5044.
[17] Yim,C.-B.; Dijkgraaf,I.; Merkx,R.; Versluis,C.; Eek,A.; Mulder,G.E.; Rijkers,D.T.S.; Boerman,O.C.; Liskamp,R.M.J.J.Med.Chem.2010,53,3944.
[18] Li,X.; Lin,Y.; Wang,Q.; Yuan,Y.; Zhang,H.; Qian,X.Eur.J.Med.Chem.2011,46,1274.
[19] Stefely,J.A.; Palchaudhuri,R.; Miller,P.A.; Peterson,R.J.; Moraski,G.C.; Hergenrother,P.J.; Miller,M.J.J.Med.Chem.2010,53,3389.
[20] Singh,P.; Raj,R.; Kumar,V.; Mahajan,M.P.; Bedi,P.M.S.; Kaur,T.; Saxena,A.K.Eur.J.Med.Chem.2012,47,594.
[21] Len,C.; Boulogne-Merlot,A.-S.; Postel,D.; Ronco,G.; Villa,P.; Goubert,C.; Jeufrault,E.; Mathon,B.; Simon,H.J.Agric.Food Chem.1996,44,2856.
[22] Imamura,H.; Ohtake,N.; Jona,H.; Shimizu,A.; Moriya,M.; Sato,H.; Sugimoto,Y.; Ikeura,C.; Kiyonaga,H.; Nakano,M.; Nagano,R.; Abe,S.; Yamada,K.; Hashizume,T.; Morishima,H.Biorg.Med.Chem.2001,9,1571.
[23] Carta,F.; Aggarwal,M.; Maresca,A.; Scozzafava,A.; McKenna,R.; Masini,E.; Supuran,C.T.J.Med.Chem.2012,55,1721.
[24] Huang,W.; Ding,Y.; Miao,Y.; Liu,M.-Z.; Li,Y.; Yang,G.-F.Eur.J.Med.Chem.2009,44,3687.
[25] Hou,X.-L.; Ge,Z.-M.; Wang,T.-M.; Guo,W.; Cui,J.-R.; Cheng,T.-M.; Lai,C.-S.; Li,R.-T.Bioorg.Med.Chem.Lett.2006,16,4214.
[26] Hou,X.-L.; Ge,Z.-M.; Wang,T.-M.; Guo,W.; Wu,J.; Cui,J.-R.; Lai,C.-S.; Li,R.-T.Arch.Pharm.2011,11,320.
[27] Chen,C.-X.; Li,X.-Q.; Li,T.-C.; Zhou,X.-Z.Acta Chim.Sinica 2012,70,852 (in Chinese)(陈凑喜,李学强,李天才,周学章,化学学报,2012,70,852.)
[28] Cao,S.-L.; Wang,Y.; Zhu,L.; Liao,J.; Guo,Y.-W.; Chen,L.-L.; Liu,H.-Q.; Xu,X.Eur.J.Med.Chem.2010,45,3850.
[29] Qian,Y.; Ma,G.-Y.; Yang,Y.; Cheng,K.; Zheng,Q.-Z.; Mao,W.-J.; Shi,L.; Zhao,J.; Zhu,H.-L.Biorg.Med.Chem.2010,18,4310.
[30] Wang,X.-J.; Xu,H.-W.; Guo,L.-L.; Zheng,J.-X.; Xu,B.; Guo,X.; Zheng,C.-X.; Liu,H.-M.Bioorg.Med.Chem.Lett.2011,21,3074.
[31] Wang,X.-J.; Xu,H.-W.; Guo,L.-L.; Zhang,E.; Chen,G.-W.; Guo,X.; Liu,H.-M.Heterocycles 2011,83,1005.
[32] Duan,Y.-C.; Ma,Y.-C.; Zhang,E.; Shi,X.-J.; Wang,M.-M.; Ye,X.-W.; Liu,H.-M.Eur.J.Med.Chem.2013,62,11.
[33] Duan,Y.-C.; Zheng,Y.-C.; Li,X.-C.; Wang,M.-M.; Ye,X.-W.; Guan,Y.-Y.; Liu,G.-Z.; Zheng,J.-X.; Liu,H.-M.Eur.J.Med.Chem.2013,64,99.
[34] Lin,W.; Long,L.; Feng,J.; Wang,B.; Guo,C.Eur.J.Org.Chem.2007,26,4301.
[35] Badía,C.; Souard,F.; Vicent,C.J.Org.Chem.2012,77,10870.
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