Cobalt (II) Complex of 6,7-Dicycanodipyridoquinoxaline with Antitumor Activities: Synthesis, Crystal Structure and Binding with DNA

Abstract

Abstract: A novel complex Co (II) with the planar ligand 6,7-dicycanodipyrido[2,2-d:2',3'-f]quinoxaline (L), [CoL(NO3)2(CH3CN)] (1) has been synthesized and characterized. The crystal structure of the complex was determined by X ray diffraction analysis. The cobalt atom was heptacoordinated to form a distorted pentagonal bipyramid geometry by three nitrogen atoms of L and a CH3CN, four oxygen atoms of two NO3^- in complex 1. Biological tests against four different cell lines (HL-60, KB, Hela and BGC-823) showed that the complex had strong antitumor properties with the 50% inhibition concentrations (IC50) of the complex were in a μmol·L^-1 range. For understanding the antitumor mechanism of the complex, the binding modes of the complex with calf thymus DNA had also been investigated with spectrophotometric methods, viscosity and thermal denaturation measurements. The experimental results indicated that complex 1 intercalated into DNA base pairs. The intrinsic binding constant Kb values for 1 (4.43×10⁵mol·L^-1) and L (1.65×10⁵mol·L^-1) were determined by absorption titration and calculated with the model of McGhee and Von Hippel.

Key words: Cobalt(II)Complex6,7-Dicycanodipyrido[2,2-d:2',3'-f]quinoxaline, Cobalt(II)Complex6,7-Dicycanodipyrido[2,2-d:2',3'-f]quinoxaline, Antitumor activity, Antitumor activity, Crystal structure, Crystal structure, Interaction with DNA, Interaction with DNA

Supporting:

Xu Zhidong, Liu He, Wang Min, Xiao Sulong, Yang Ming^*, Bu Xianhe . Cobalt (II) Complex of 6,7-Dicycanodipyridoquinoxaline with Antitumor Activities: Synthesis, Crystal Structure and Binding with DNA[J]. .

References

[1] Williams DR. [J] Chem Rev, 1972, 72: 203.
[2] Kepper BK. [P] DE: 19701692, 1998.
[3] Lincoln P and Norden B. [P] WO: 9915535, 1999.
[4] Long GV, Harding MM, Fan JY and Denny WA. [J] Anticancer Drug Des, 1997, 12: 453.
[5] Soedjak HS, Cano RE, Tran L, Bales BL and Hajolu J . [J] Biochim Biophys Acta, 1997, 135: 305.
[6] Keppler BK. [J] Prog Clin Biochem Med. 1989, 10: 41.
[7] Heim ME, Flechtner H and Keppler BK. [J] Prog Chin Biochem Med, 1989, 10: 218.
[8] Ross M, Gielen M, Lelieveld P and Vos Dde. [J] Anticancer Res, 1990, 10: 1397.
[9] Quiroga AG, Pérez JM, López-Solera I, Montero EI, Masaguer JR and Alonso C. [J] J Inorg Biochem, 1998, 69: 275.
[10] Depenbrock H, Schmelcher S, Peter R, Keppler BK, Weirich G, Block T, Rastetter J and Hanauske AR. [J] Eur J Cancer, 1997, 33: 2404.
[11] Li VS, Choi D, Wang Z, Jimenez LS, Tang MS and Kohn H. [J] J Am Chem Soc, 1996, 118: 2326.
[12] Tomasz M, Lipman R, Chowdary D, Pawlak J, Verdine GL and Nakanishi K. [J] Science, 1987, 235: 1204.
[13] Hecht SM. [J] J Nat Prod, 2000, 63: 158.
[14] Zuber G, Quada JCJr and Hecht SM. [J] J Am Chem Soc, 1998, 120: 9368.
[15] Jamieson ER and Lippard SJ . [J] Chem Rev, 1999, 99: 2467.
[16] Lepre CA and Lippard SJ . In Nucleic Acids and Molecular Biology [M] . Berlin: Springer Press. 1990, 4: 9.
[17] Yang M, Xiao SL, Zhou TY, Zhang JM and Wang K. [J] J Beijing Med Univ, 2000, 32: 198
[18] Barton JK, Goldberg JM, Kumar CV and Turro NJ . [J] J Am Chem Soc, 1986, 108: 2081.
[19] Jenkins Y, Friedman AE, Turro NJ and Barton JK. [J] Biochemistry, 1992, 31: 10809.
[20] Arkin MR, Stemp EDA, Holmlin RE, Barton JK, HÊrmann A, Olson EJC and Barbara PF. [J] Science, 1996, 273: 475.
[21] Fijita M. [J] Chem Soc Rev, 1998, 27: 417.
[22] Holmlin RE and Barton JK. [J] Inorg Chem, 1995, 34: 7.
[23] Arounaguiri S and Maiya BG. [J] Inorg Chem, 1999, 38: 842.
[24] Ambroise A and Maiya BG. [J] Inorg Chem, 2000, 39: 4264.
[25] Chaires JB, Dattagupta N and Crothers DM. [J] Biochemistry, 1982, 21: 3933.
[26] Wells RD, Larson J E, Grant RC, Shortle BE and Cantor CR. [J] J Mol Biol, 1970, 54: 465.
[27] Liu JG, Ye BH, Li H, Zhen QX, Ji LN and Fu YH. [J] J Inorg Biochem, 1999, 76: 265.
[28] McGhee JD and Von Hippel PH. [J] J Mol Biol, 1974, 86: 469.
[29] Stevenson KA, Yen SF, Yang NC, Boykin DW and Wilson WD. [J] J Med Chem, 1984, 27: 1677.
[30] Yang M, Wang K, Zang CB, Wang BH and Zhang YM. [J] J Chin Pharm Sci, 1994, 3: 51.
[31] Pyle AM, Rehmann JP, Meshoyrer R, Kumar CV, Turro NJ and Barton JK. [J] J Am Chem Soc, 1989, 111: 3051.
[32] Long EC and Barton JK. [J] ACC Chem Res, 1990, 23: 271.
[33] Eriksson M, Leijon M, Hiort C, Nordén B and Gräslund A. [J] J Am Chem Soc, 1992, 114: 4933.
[34] Satyanarayana S, Dabrowiak JC and Chaires JB. [J] Biochemistry, 1992, 31: 9319.
[35] Barton JK, Danishefsky AT and Goldberg JM. [J] J Am Chem Soc, 1984, 106: 2172.
[36] Friedman AE, Chambron JC, Sauvage JP, Turro NJ and Barton JK. [J] J Am Chem Soc, 1990, 112: 4960.