Phenanthroline Copper, Manganese, Cobalt With The Material And Its Anti-cancer Anti-tumor Activity

The development of new Pharmaceuticals has undergone a substantial change over the past decade and continues to change rapidly. Despite, or perhaps because of these changes, the number of new chemical entities being registered as Pharmaceuticals has fallen to a historic low. This poses a major threat to human health and the viability of pharmaceutical industry at a time when new therapies are urgently needed for treating cancer, viral diseases (e.g. bird flu), antibiotic-resistant bacterial infections, and the many consequences of the obesity epidemic. Especially in the area of anticancer, since the discovery of cisplatin for cancer treatment, numerous transition metal complexes have been synthesized and screened for their anticancer properties. Among the transition metal complexes, the transition metal-pyridyl complexes have become research hotspot of many correlative subjects, as a result of the extensive application in the area such as electrochemistry, photochemistry, photochemical catalysis, biochemistry and so on.1,10-phenanthroline (phen) and substituted derivatives as ligands can coordinate with transition metals and disturb the several functions of biological systems. Therefore, we choose bis-bidentate chelating ligand-phen, which can connect with DNA in many ways, to react with some transition metals-Cu,Mn and Co, which possess anticancer activity under the normal or thermal condition, and get a series of novel metal-organic compounds which have been characterized by X-ray crystal, anticancer activity and some related spectra.(1) A chiral complex [Cu(NO₃)₂(phen)(DMF)] (phen =1,10-phenanthroline, DMF=N,N- dimethylformamide) has been synthesized by the reaction of 1,10-phenanthroline(phen) with Cu(NO₃)₂·3H₂O under room temperature. The structure has been characterized by elemental analysis, 1R, UV spectra, EPR, CD and single-crystal X-ray diffraction. The crystal belongs to triclinic. Its space group is P1 withα=8.4859(2)(?), b= 9.6846(3)(?), c=11.4354(3)(?),α= 101.411(2)°,β=95.094(2)°,γ=98.234(2)°. The title complex contains a five-coordinated copper(Ⅱ) center, which is surrounded by two N atoms of phen ligand, two nitrate O atoms (Cu-O=2.085(6)(?)) and one O atom of DMF (Cu-O=1.929(6)(?)). The complex is sensitive to EPR and exists a negative cotton effect at 295 nm and a positive cotton effect at 371.2 nm in CD spectrum. The compound is tested in vitro. The inhibition rate of complex for human tumor cell lines, A-549, Bel-7402 and HCT, in 5μg/mL is 84.28%, 95.94% and 90.62%, respectively; the inhibition rate of complex for human tumor cell lines, HL-60, BGC-832, Bel-7402 and KB, in 10μg/mL is 90.48%, 95.49%, 94.73% and 95.57%, respectively. IC₅₀ of the complex for HCT and A-549 is 0.68 and 0.80, respectively. The experiment data is better than clinical anticancer drug 5-Fu. It suggests that the complex possesses high anticancer activity.(2) A novel bridge two-nucleus complex [Mn₂(SO₄)₂(phen)₄] (phen = 1,10-phenanthroline) has been synthesized by the reaction of 1,10-phenanthroline (phen) with MnSO₄·H₂O under room temperature. The structure has been characterized by elemental analysis, IR, UV, EPR and single-crystal X-ray diffraction. The crystal belongs to monoclinic. Its space group is P21/n with a = 11.5603(2) (?), b = 16.8155(3) (?), c = 12.1111(2) (?),α= 90.00°,β= 93.8420(10)°,γ= 90.00°. The title complex contains a six-coordinated manganese(Ⅱ) center, which is surrounded by four N atoms of phen ligand and two sulfate O atom (Mn-O = 2.0960(15)-2.1203(16) (?)). Mn-N bond length is in the range of 2.2674(19)A to 2.3441 (18)(?). The complex is sensitive to EPR. The compound is tested in vitro. The inhibition rate of complex for human tumor cell lines, A-549, Bel-7402 and HCT, in 5μg/mL is 79.63%, 83.73% and 84.35%, respectively; the inhibition rate of complex for human tumor cell lines, HL-60, BGC-832, Bel-7402 and KB, in 10μg/mL is 87.63%, 62.74%, 72.51% and 26.41%, respectively. IC₅₀ of the complex for HCT and A-549 is 1.09 and 0.83, respectively. The experiment data is better than clinical anticancer drug 5-Fu. It suggests that the complex possesses high anticancer activity.(3) A novel cobalt complex [Co(SO₄)(phen)(OH)(H₂O)₂] (phen = 1,10-phenanthroline) has been synthesized by the reaction of 1,10-phenanthroline (phen) with CoSO₄·7H₂O under room temperature condition. The structure has been characterized by elemental analysis, IR, UV and single-crystal X-ray diffraction. The crystal belongs to Monoclinic. Its space group is P2(1)/c with a = 11.8958(2) (?), b = 10.0432(2) (?), c = 13.6000(3) (?),β= 111.9870(10)°. The complex contains a six-coordinated cobalt(Ⅲ) center, which is surrounded by two N atoms of phen ligand(Co-N = 2.1376(13)-2.1501(15)(?)), one sulfate O atom (Co-O = 2.0778(12)(?)), one hydroxyl O atom(Co-O = 2.1373(12) (?)) and two water molecule (Co-O = 2.0731 (12)-2.0906(13) (?)). The hydrogen bonds lead to the formation of a 3-D network structure. The compound is tested in vitro. The inhibition rate of complex for human tumor cell lines, A-549, Bel-7402 and HCT, in 5μg/mL is -13.93%, -3.68% and -3.20%, respectively. The experiment data shows that the complex exhibits negative activity against the cancer cell above and possesses low anticancer activity.Integrating the experiment results of (1), (2) and (3), we think that there exist some anticancer activity differences among the complexes which have same ligand but different central metal ions. It shows that the central metal may play more important part in the reaction with cancer cell.(4) A novel cobalt complex [Co(C₅O₂H₇)₂(C₈N₂H₇)(H₂O)] (C₅O₂H₇ = acetylacetonate, C₈N₂H₇ = 2-methyl-benzoimidazole) has been synthesized under solvothermal condition. Its structure has been determined by X-ray diffraction method. The crystal belongs to Monoclinic. Its space group is P21/c with a= 19.086(3) (?), b = 14.4757(19) (?), c = 14.5910(18)(?),β= 94.475(4)°. The complex contains a six-coordinated cobalt(Ⅱ) center, which is surrounded by one N atom of 2-methyl-benzoimidazoIe ligand(Co-N = 2.178(7) (?)), one O atom from water (Co-O= 2.256(6) (?)) and four acetylacetonate O atoms with the Co-O bond lengths in the range of 2.027(6)(?) to 2.057(6)(?). 2-methyl-benzoimidazole, which is synthesized in the process of reaction, participates in coordination. The hydrogen bonds lead to the formation of a 3-D network structure. IR, UV and reaction mechanism have been investigated.