SIOC 中文
CJOG
Adv search

Chinese Journal of Organic Chemistry >

2021 , Vol. 41 >Issue 4: 1599 - 1606

DOI: https://doi.org/10.6023/cjoc202008015

ARTICLES

Synthesis and Anti-tumor Effects of Naphthalimide Derivatives Targeted in Cell Nucleus

  • Ruixue Rong ,
  • Jimin Li ,
  • Yaowen Li ,
  • Xiaoyu Guo ,
  • Chong Wang ,
  • Yanjun Li ,
  • Jinmei Li ,
  • Baojun Han ,
  • Zhiran Cao ,
  • Kerang Wang ,
  • Xiaoliu Li
Expand
  • a College of Basic Medicine, Key Laboratory of Pathogenesis Mechanism and Control of Inflammatory-autoimmune Diseases in Hebei Province, Hebei University, Baoding, Hebei 071000
    b College of Chemistry and Environmental Science, Key Laboratory of Medicinal Chemistry and Molecular Diagnosis (Ministry of Education), Key Laboratory of Chemical Biology of Hebei Province, Hebei University, Baoding, Hebei 071002
    c Forth Department of Orthopedic, Baoding First Central Hospital, Baoding, Hebei 071000
    d Department of Pathology, Baoding First Central Hospital, Baoding, Hebei 071000
* Corresponding authors. E-mail: ;
E-mail:

Received date: 2020-08-11

  Revised date: 2020-09-15

  Online published: 2020-12-31

Supported by

National Natural Science Foundation of China(21572044); National Natural Science Foundation of China(21778013); Natural Science Foundation of Hebei Province(B2017201193); Foundation of Health Commission of Hebei Province(20202217); Innovation Project of Students(201910075009); Innovation Project of Students(2020338); Hebei University High-level Talent Research Startup Project(521000981311)

Fold

Abstract

A series of novel chiral amino alcohol modified naphthalimide derivatives NI1~NI8 were designed and synthesized by nucleophilic substitution reaction. Furthermore, their cytotoxicities were studied by thiazolyl blue tetrazolium bromide (MTT) method. The cytotoxicity of the R-type isomer in the naphthalimide derivatives with primary hydroxyl amino alcohol modification was better than that of the S-type isomer. In addition, deoxyribonucleic acid (DNA) binding interactions and fluorescence imaging of (R)-2-(2-(dimethylamino)ethyl)-6-((1-hydroxypropan-2-yl)amino)-naphthalimide (NI1) and (S)-2-(2-(dimethylamino)ethyl)-6-((1-hydroxypropan-2-yl)amino)-naphthalimid (NI2) with Ct-DNA and HeLa cells were investigated. NI1 and NI2 showed strong binding interactions with Ct-DNA with a bonding constant of 104 L/mol. And NI1 and NI2 exhibited nucleus-targeting imaging for HeLa cells. NI1 and NI2 mainly arrested the S phase. Moreover, the hematoxic results of NI1in mice showed no significant effects on the red blood cells, white blood cells and platelets in the blood.

Key words： naphthalimide; nucleus; chiral; cell cycle

Cite this article

Ruixue Rong , Jimin Li , Yaowen Li , Xiaoyu Guo , Chong Wang , Yanjun Li , Jinmei Li , Baojun Han , Zhiran Cao , Kerang Wang , Xiaoliu Li . Synthesis and Anti-tumor Effects of Naphthalimide Derivatives Targeted in Cell Nucleus[J]. Chinese Journal of Organic Chemistry, 2021 , 41(4) : 1599 -1606 . DOI: 10.6023/cjoc202008015

References

[1]
Tiwari, R.; Jain, P.; Asati, S.; Haider, T.; Soni, V.; Pandey, V. J. Drug Delivery Sci. Technol. 2018, 48,383.
[2]
Wang, G.H.; Chen, H.; Cai, Y.Y.; Li, L.; Yang, H.K.; Li, Q.; He, Z.J.; Lin, J.T. Mater. Sci. Eng. C 2018, 90,568.
[3]
(a) Ahmad, M.Z.; Akhter, S.; Rahman, Z.; Akhter, S.; Anwar, M.; Mallik, N.; Ahmad, F.J. J. Pharm. Pharmacol. 2013, 65,634.
[3]
(b) Ali, M.R. K.; Wu, Y.; Ghosh, D.; Do, B.H.; Chen, K.; Dawson, M.R.; Fang, N.; Sulchek, T.A.; El-Sayed, M.A. ACS Nano 2017, 11,3716.
[4]
(a) Pan, L.M.; Shi, J.L. Chin. J. Chem. 2018, 36,481.
[4]
(b) Marshall, W.F. Curr. Biol. 2002, 12,185.
[5]
Dey, P. Diagn. Cytopathol. 2010, 38,382.
[6]
Zink, D.; Fischer, A.H.; Nickerson, J.A. Nat. Rev. Cancer 2004, 4,677.
[7]
Peng, H.B.; Tang, J.; Zheng, R.; Guo, G.N.; Dong, A.G.; Wang, Y.J.; Yang, W.L. Adv. Healthcare Mater. 2017, 6,1601289.
[8]
(a) Michalak, E.M.; Burr, M.L.; Bannister, A.J.; Dawson, M.A. Nat. Rev. Mol. Cell Biol. 2019, 20,573.
[8]
(b) Tandon, R.; Luxami, V.; Kaur, H.; Tandon, K.; Paul, K. Chem. Rec. 2017, 17,956.
[9]
Zhou, J.; Chang, A.; Wang, L.L.; Liu, Y.; Liu, X.J.; Shangguan, D.H. Org. Biomol. Chem. 2014, 56,9207.
[10]
Zhang, H.; Wang, K.; Xuan, X.P.; Lv, Q.Z.; Nie, Y.M.; Guo, H.M. Chem. Commun. 2016, 52,6308.
[11]
Singh, K.; Rotaru, A.M.; Beharry, A.A. ACS Chem. Biol. 2018, 13,1785.
[12]
Skok, ?.; Zidar, N.; Kikelj, D.; Ila?, J. J. Med. Chem. 2020, 63,884.
[13]
Liu, J.; Liu, X.J.; Lu, S.S.; Zhang, L.L.; Feng, L.; Zhong, S.L.; Zhang, N.; Bing, T.; Shangguan, D.H. Analyst 2020, 145,6549.
[14]
Fueyo-González, F.; Fernández-Gutiérrez, M.; García-Puentes, D.; Orte, A.; González-Vera, J.A.; Herranz, R. Eur. J. Med. Chem., 2020, 200,112407.
[15]
Wu, Z.; Liu, M.; Liu, Z.; Tian, Y. J. Am. Chem. Soc. 2020, 142,7532.
[16]
Feng, H.; Meng, Q.T.; Ta, H.T.; Zhang, R. New J. Chem. 2020, 44,12890.
[17]
Wang, K.R.; Qian, F.; Sun, Q.; Ma, C.L.; Rong, R.X.; Cao, Z.R.; Wang, X.M.; Li, X.L. Chem. Biol. Drug Des. 2016, 87,664.
[18]
Rong, R.X.; Wang, S.S.; Liu, X.; Li, R.F.; Wang, K.R.; Cao, Z.R.; Li, X.L. Bioorg. Med. Chem. Lett. 2018, 28,742.
[19]
Wang, K.R.; Qian, F.; Rong, R.X.; Cao, Z.R.; Wang, X.M.; Li, X.L. RSC Adv. 2014, 4,47605.
[20]
Rong, R.X.; Sun, Q.; Ma, C.L.; Chen, B.; Wang, W.Y.; Wang, Z.A.; Wang, K.R.; Li, X.L. Med. Chem. Commun. 2016, 7,679.
[21]
Wang, K.R.; An, H.W.; Wang, Y.Q.; Yan, X.H.; Li, Y.; Chen, H.; Zhang, P.Z.; Li, J.M.; Li, X.L.; Zhang, J.C. Chin. J. Org. Chem. 2012, 32,696. (in Chinese)
[21]
( 王克让, 安红维, 王月清, 闫新豪, 李锐, 陈华, 张平竹, 李金梅, 李小六, 张金超, 有机化学, 2012, 32,696.)
[22]
Sharma, H.; Sidhu, J.S.; Hassen, W.M.; Singh, N.; Dubowski, J.J. ACS Omega 2019, 4,5829.
[23]
Elmes, R.B. P.; Ryan, G.J.; Erby, M.L.; Frimannsson, D.O.; Kitchen, J.A.; Lawler, M.; Williams, D.C.; Quinn, S.J.; Gunnlaugsson, T. Inorg. Chem. 2020, 59,10874.
[24]
Petrova, N.V.; Velichko, A.K.; Razin, S.V.; Kantidze, O.L. Cell Cycle 2016, 15,337.
[25]
(a) Bai, T.; Zhu, B.; Shao, D.; Lian, Z.; Liu, P.; Shi, J.; Kong, J. Macromol. Biosci. 2020, 20,e1900438.
[25]
(b) Wang, S.S.; Zhang, Q.L.; Chu, P.; Kong, L.Q.; Li, G.Z.; Li, Y.Q.; Yang, L.; Zhao, W.J.; Guo, X.H.; Tang, Z.Y. Bioorg. Chem. 2020, 101,104036.
[26]
Wang, K.R.; Qian, F.; Wang, X.M.; Tan, G.H.; Rong, R.X.; Cao, Z.R.; Chen, H.; Zhang, P.Z.; Li, X.L. Chin. Chem. Lett. 2014, 25,1087.
[27]
Banerjee, S.; Veale, E.B.; Phelan, C.M.; Murphy, S.A.; Tocci, G.M.; Gillespie, L.J.; Frimannsson, D.O.; Kelly, J.M.; Gunnlaugsson, T. Chem. Soc. Rev. 2013, 42,1601.
Options
Outlines

/

〈 〉