Citation: Ke-Rang Wang, Feng Qian, Xiao-Man Wang, Guan-Hai Tan, Rui-Xue Rong, Zhi-Ran Cao, Hua Chen, Ping-Zhu Zhang, Xiao-Liu Li. Cytotoxic activity and DNA binding of naphthalimide derivatives with amino acid and dichloroacetamide functionalizations[J]. Chinese Chemical Letters, ;2014, 25(7): 1087-1093. doi: 10.1016/j.cclet.2014.04.020 shu

Cytotoxic activity and DNA binding of naphthalimide derivatives with amino acid and dichloroacetamide functionalizations

Ke-Rang Wang ^a,b,, ,
Feng Qian ^a ,
Xiao-Man Wang ^c ,
Guan-Hai Tan ^a ,
Rui-Xue Rong ^c ,
Zhi-Ran Cao ^c ,
Hua Chen ^a,b ,
Ping-Zhu Zhang ^a,b ,
Xiao-Liu Li ^a,b,,

1.
a Key Laboratory of Chemical Biology of Hebei Province, College of Chemistry and Environmental Science, Hebei University, Baoding 071002, China;
2.
b Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of Ministry of Education, Hebei University, Baoding 071002, China;
3.
c Department of Immunology, School of Basic Medical Science, Hebei University, Baoding 071002, China

Corresponding author: Ke-Rang Wang, Xiao-Liu Li,
Received Date: 5 March 2014
Available Online: 9 April 2014
Fund Project: the Foundation of Hebei Education Department (No. YQ2013006). (No. B2012201041)

A series of novel naphthalimide derivatives modified by amino acids and their dichloroacetamide derivatives at the 3-position have been synthesized. Their cytotoxic activities were preliminarily evaluated against Hela, A549 and K562 cells, which showed that the length of the side chains of the amino acids influenced the cytotoxic activities. Moreover, compound 7d showed a very good cytotoxic activity against A549 cells with an IC₅₀ value of 4.78 mmol L^-1. Furthermore, the UV-vis, fluorescence, and circular dichroism (CD) spectroscopies and thermal denaturation experiment indicated that compounds 6a, 6d and 7a, 7d, as DNA intercalators, exhibited binding affinities with calf-thymus DNA (Ct-DNA).
- Naphthalimide,
- Dichloroacetamide,
- Cytotoxic activity,
- DNA binding
1. [1]
  [1] M.F. Braña, A. Ramos, Naphthalimides as anti-cancer agents: synthesis and biological activity, Curr. Med. Chem. -Anticancer Agents 1 (2001) 237-255.
2. [2]
  [2] L. Ingrassia, F. Lefranc, R. Kiss, T. Mijatovic, Naphthalimides and azonafides as promising anti-cancer agents, Curr. Med. Chem. 16 (2009) 1192-1213.
3. [3]
  [3] M. Lv, H. Xu, Overview of naphthalimide analogs as anticancer agents, Curr. Med. Chem. 16 (2009) 4797-4813.
4. [4]
  [4] T. Mijatovic, T. Mahieu, C. Bruyère, et al., UNBS5162, a novel naphthalimide that decreases CXCL chemokine expression in experimental prostate cancers, Neoplasia 10 (2008) 573-586.
5. [5]
  [5] E.V. Quaquebeke, T. Mahieu, P. Dumont, et al., 2,2,2-Trichloro-N-({2-[2-(dimethylamino) ethyl]-1,3-dioxo-2,3-dihydro-1H-benzo[de]isoquinolin-5-yl}carbamoyl) acetamide (UNBS3157), a novel nonhematotoxic naphthalimide derivative with potent antitumor activity, J. Med. Chem. 50 (2007) 4122-4134.
6. [6]
  [6] A. Kamal, N.R. Bolla, P.S. Srikanth, A.K. Srivastava, Naphthalimide derivatives with therapeutic characteristics: a patent review, Expert. Opin. Ther. Patents 23 (2013) 299-317.
7. [7]
  [7] S. Banerjee, E.B. Veale, C.M. Phelan, et al., Recent advances in the development of 1,8-naphthalimide based DNA targeting binders, anticancer and fluorescent cellular imaging agents, Chem. Soc. Rev. 42 (2013) 1601-1618.
8. [8]
  [8] S.Y. Tan, H. Yin, Z. Chen, X.H. Qian, Y.F. Xu, Oxo-heterocyclic fused naphthalimides as antitumor agents: synthesis and biological evaluation, Eur. J. Med. Chem. 62 (2013) 130-138.
9. [9]
  [9] D. Mahadevan, D.W. Northfelt, P. Chalasani, et al., Phase I trial of UNBS5162, a novel naphthalimide in patients with advanced solid tumors or lymphoma, Int. J. Clin. Oncol. 18 (2013) 934-941.
10. [10]
  [10] D.A. Tennant, R.V. Duraán, E. Gottlieb, Targeting metabolic transformation for cancer therapy, Nat. Rev. Cancer 10 (2010) 267-277.
11. [11]
  [11] I. Papandreou, T. Goliasova, N.C. Denko, Anticancer drugs that target metabolism: is dichloroacetate the new paradigm? Int. J. Cancer 128 (2011) 1001-1008.
12. [12]
  [12] C. Granchi, F. Minutolo, Anticancer agents that counteract tumor glycolysis, ChemMedChem 7 (2012) 1318-1350.
13. [13]
  [13] F. Wang, M.A. Ogasawara, P. Huang, Small mitochondria-targeting molecules as anti-cancer agents, Mol. Aspects Med. 31 (2010) 75-92.
14. [14]
  [14] J.S. Butler, P.J. Sadler, Targeted delivery of platinum-based anticancer complexes, Curr. Opin. Chem. Biol. 17 (2013) 175-188.
15. [15]
  [15] S. Dhar, S.J. Lippard, Mitaplatin, a potent fusion of cisplatin and the orphan drug dichloroacetate, Proc. Natl. Acad. Sci. U. S. A. 106 (2009) 22199-22204.
16. [16]
  [16] H.H. Xiao, L.S. Yan, Y. Zhang, et al., A dual-targeting hybrid platinum(IV) prodrug for enhancing efficacy, Chem. Commun. 48 (2012) 10730-10732.
17. [17]
  [17] X.Xue, S.You,Q.Zhang, et al.,Mitaplatinincreases sensitivity of tumor cells tocisplatin by inducing mitochondrial dysfunction, Mol. Pharmacol. 9 (2012) 634-644.
18. [18]
  [18] Y.C. Yang, P.H. Shang, C.M. Cheng, et al., Novel N-phenyl dichloroacetamide derivatives as anticancer reagents: design, synthesis and biological evaluation, Eur. J. Med. Chem. 45 (2010) 4300-4306.
19. [19]
  [19] T.W. Li, Y.C. Yang, C.M. Cheng, et al., Design, synthesis and biological evaluation of N-arylphenyl-2,2-dichloroacetamide analogues as anti-cancer agents, Bioorg. Med. Chem. Lett. 22 (2012) 7268-7271.
20. [20]
  [20] T.W. Li, Y.C. Yong, C.M. Cheng, et al., Multi-substituted N-phenyl-2,2-dichloroacetamide analogues as anti-cancer drugs: design, synthesis and biological evaluation, Acta Pharm. Sin. 47 (2012) 354-363.
21. [21]
  [21] J.A. Montgomery, A.T. Shortnacy, D.A. Carson, J.A. Secrist III, Synthesis and biological evaluation of irreversible inhibitors of aldose reductase, J. Med. Chem. 29 (1986) 2384-2389.
22. [22]
  [22] E.C. Long, J.K. Barton, On demonstrating DNA intercalation, Acc. Chem. Res. 23 (1990) 271-273.
23. [23]
  [23] X. Yang, W. Liu, W. Jin, G. Shen, R. Yu, DNA binding studies of a solvatochromic fluorescence probe 3-methoxybenzanthrone, Spectrochim. Acta A 55 (1999) 2719-2727.
24. [24]
  [24] L.J. Xie, Y.F. Xu, F. Wang, et al., Synthesis of new amonafide analogues via coupling reaction and their cytotoxic evaluation and DNA-binding studies, Bioorg. Med. Chem. 17 (2009) 804-810.
25. [25]
  [25] M. Kožurkovaá, D. Sabolovaá, H. Paulíkovaá, et al., DNA binding properties and evaluation of cytotoxic activity of 9,10-bis-N-substituted (aminomethyl)anthracenes, Int. J. Biol. Macromol. 41 (2007) 415-422.
26. [26]
  [26] P. Uma Maheswari, M. Palaniandavar, DNA binding and cleavage activity of[Ru(NH₃)₄(diimide)]Cl₂ complexes, Inorg. Chim. Acta 357 (2004) 901-912.
27. [27]
  [27] X. Jiang, L. Shang, Z.X. Wang, S.J. Dong, Spectrometric and voltammetric investigation of interaction of neutral red with calf thymus DNA: pH effect, Biophys. Chem. 118 (2005) 42-50.
28. [28]
  [28] P.U. Maheswari, M. Palaniandavar, DNA binding and cleavage properties of certain tetrammine ruthenium(II) complexes of modified 1,10-phenanthrolines: effect of hydrogen-bonding on DNA-binding affinity, J. Inorg. Biochem. 98 (2004) 219-230.
29. [29]
  [29] X.L. Li, Y.J. Lin, Q.Q. Wang, et al., The novel anti-tumor agents of 4-triazol-1,8-naphthalimides: synthesis, cytotoxicity, DNA intercalation and photocleavage, Eur. J. Med. Chem. 46 (2011) 1274-1279.
30. [30]
  [30] Z.C. Zhang, Y.Y. Yang, D.N. Zhang, et al., Acenaphtho[1,2-b]pyrrole derivatives as new family of intercalators: various DNA binding geometry and interesting antitumor capacity, Bioorg. Med. Chem. 14 (2006) 6962-6970.
31. [31]
  [31] U. Chaveerach, A. Meenongwa, Y. Trongpanich, C. Soikum, P. Chaveerach, DNA binding and cleavage behaviors of copper(II) complexes with amidino-O-methylurea and N-methylphenyl-amidino-O-methylurea, and their antibacterial activities, Polyhedron 29 (2010) 731-738.
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