A theoretical study on interactions between Berberine as an anticancer drug and DNA


Department of Applied Chemistry, Ardabil branch, Islamic Azad University, Ardabil, Iran


In this study, we present the work on the physicochemical interaction between the anti-cancer alkaloid
berberine (BRB) and DNA with the purpose of designing drugs that interact more with DNA. Molecular
modeling on the complex formed between berberine and DNA presented that this complex was undeniably
fully able of participating in the formation of a stable intercalation site. Besides, the molecular geometries of
berberine and the DNA bases (Adenine, Guanine, Cytosine and Thymine) were optimized with the aid of the
B3LYP/6-31G method. This intercalator has a large polarizability and is a good electron acceptor, while base
pairs are good electron donors. B3LYP/6-31G stabilization energies of intercalator… DNA base pair
complexes are large (-7.65 kcal/mol for AT···BRB and -3.58 kcal/mol for GC···BRB). It was eventually
concluded that the dispersion energy and the electrostatic interaction influenced the stability of the
intercalator···DNA base pair complexes. The results exhibited that the BRB changes affected the DNA
structure with reference to the bond length, the bond angle, the torsion angle and the charges.


[1] D.S. Bhakuni, S. Jain, in The Alkaloids (Brossi, A.,ed.), Vol. 28, pp. 95-181, Academic Press, New York,
[2] W.A. Creasy, Biochem. Pharmacol. 28 (1979) 1081-1084.
[3] X. Tian, Y. Song, H. Dong, Y. Baoxian, Bioelectrochemistry 73 (2008) 18-22.
[4] M. Meyerson, J. Clin. Oncol. 18 (2000) 2626-2634..
[5] C.L. Kuo, C.C. Chou, B.Y. Yung, Cancer Lett. 93 (1995) 193-200.
[6] I.W. Yang, C.C. Chou, B.Y. Yung, Arch. Pharmacol. 354 (1996) 102-106.
[7] S. Letasiova, S. Jantova, L. Cipak,M. Muckova, Cancer Lett. 239 (2006) 254-262.
[8] P.-L. Peng, Y.-S. Hsieh, C.-J.Wang, J.-L. Hsu, F.-P. Chou, Appl. Pharmacol. 214 (2006) 8-15.
[9] M.M. Islam, R. Sinha, G.S. Kumar, Biophys. Chem. 125 (2007) 508-52.
[10] T.-K. Li, E. Bathory, E.J. LaVoie, A.R. Srinivasan, W.K. Olson, R.R. Sauers, L.F. Liu, D.S. Pilch,
Biochemistry 39 (2000) 7107-7116.
[11] S. Mazzini, M.C. Bellucci, R. Mondelli, Bioorg. Med. Chem. 11 (2003) 505-514.
[12] K. Bhadra, G. Suresh Kumar, S. Das, Md. M. Islam, M. Maiti, Bioorg. Med. Chem. 13 (2005) 4851-
[13] M.W. Davidson, I. Lopp, S. Alexander,W.D. Wilson, Nucleic Acids Res. 4 (1977) 2697-2712.
[14] D. Debnath, G. Suresh Kumar, R. Nandi, M. Maiti, Indian J. Biochem. Biophys. 26 (1989) 201-208.
[15] A. Saran, S. Srivastava, E. Coutinho, M. Maiti, Indian J. Biochem. Biophys. 32 (1995) 74-77.
[16] F. M. Chen, J. Biomol. Struct. Dyn. 1 (1983) 925-937.
[17] G. T. Walker, M. P. Stone, T. R. Krugh, Biochemistry 24 (1985) 7462-7471.
[18] C. C. Hardin, G. T. Walker, I. Jr. Tinoco, Biochemistry 27 (1988) 4178-4784.
[19] J. B. Chaires, J. Biol. Chem. 261(1986) 8899-8909.
[20] E. Jimenez-Garcia, J. Portugal, Biochemistry 31 (1992) 11641-11646.
[21] U. Diederichsen, Angew. Chem. Int. Ed. Engl. 36 (1997) 2317-2319.
[22] J.B. Chaires, Biophys. Chem. 35 (1990) 191-202.
[23] M.P. Fontaine-Aupart, H. Laguitton-Pasquier, R. Pansu, L. Brain, E. Renault, M.C. Marden, C. Rivalle,
J. Chem. Soc. Perkin. Trans. 2 (1996) 1767-1774.
[24] J. Dolenc, U. Borstnik, M. Hodoscek, J. Koller and D. Janezic, J. Mol. Struct. (TEOCHEM), 718 (2005)
[25] M. Elstner, P. Hobza, T. Frauenheim, S. Suhai and E. Kaxiras, J. Chem. Phys., 114 (2001) 5149-5155.
[26] T. M. EL-Gogary, The role of charge transfer complex formation on the overall structure activity
relationships of DNA radioprotectants and radiosensitizers. Ph.D. Thesis, Mansoura University, Egypt/De
Montfort University, Leicester, UK, 1998.
[27] M. J. Frisch, G. W. Trucks, H. B. Schlegel, G. E. Scuseria, M. A. Robb, J. R. Cheeseman, V.
G.Zakrzewski, J. A. Montgomery, R. E. Stratmann, J. C. Burant, S. Dapprich, J. M. Millam, A.
D.Daniels, K. N. Kudin, M. C. Strain, O. Farkas, J. Tomasi, V. Barone, M. Cossi, R. Cammi,
B.Mennucci, C. Pomelli, C. Adamo, S. Clifford, J. Ochterski, G. A. Petersson, P. Y. Ayala, Q. Cui,K.
Morokuma, D. K. Malick, A. D. Rabuck, K. Raghavachari, J. B. Foresman, J. Cioslowski, J. V.Ortiz, B.
B. Stefanov, G. Liu, A. Liashenko, P. Piskorz, I. Komaromi, R. Gomperts, R. L. Martin,D. J. Fox, T.
Keith, M. A. Al-Laham, C. Y. Peng, A. Nanayakkara, C. Gonzalez, M. Challacombe,P. M. W. Gill, B.
Johnson, W. Chen, M. W. Wong, J. L. Andres, C. Gonzalez, M. Head-Gordon, E.S. Replogle and J. A.
Pople, Gaussian Inc. Pittsburgh PA, 1998.
[28] C. Bayly, P. Cieplak, W.D. Cornell, P.A. Kollman, J. Phys. Chem. 97 (1993) 10269-10280.
[29] W.D. Cornell, P. Cieplak, C.I. Bayly, I.R. Gould, K.M. Merz, D.M. Ferguson, D. C. Spellmeyer, T. Fox,
J.W. Caldwell, P.A. Kollman, J. Am. Chem Soc. 117 (1995) 5179-5197. .
[30] P. Hobza, J. Sponer, T. Reschel, J. Comput. Chem. 16 (1995) 1315-1325.
[31] P. Hobza, R. Zahradnik, Intermolecular Complexes, Elsevier, Amsterdam, 1988.
A. Parchehbaf-Jadid et al., J. Iranian Chem. Res. 5 (3) (2012) 143-153
[32] J.G.C.M. van Duijneveldt-van de Rijdt, F.B. van Duijneveldt, J.H. van Lenthe, Chem. Rev. 94 (1994)
[33] U. Bren,M. Zupan, F.P. Guengerich, J. Mavri, J. Org. Chem. 71 (2006) 4078-4084.
[34] U. Bren, F.P. Guengerich, J. Mavri, Chem. Res. Toxicol. 20 (2007) 1134-1140.
[35] M.J. Frisch, J.E.Del-Bene; J. S. Binkley, H.F. Schaefer, J. Chem. Phys. 84 (1986) 2279-2286.
[36] D.W. Schwenke, D.G. Truhlar, J. Chem. Phys. 82 (1985) 2418-2432.