Synthesis, crystal structure, cytotoxic activity and DNA-binding properties of the copper (II) and zinc (II) complexes with 1-[3-(2-pyridyl)pyrazol-1-ylmethyl]naphthalene.
A new ligand L, 1-[3-(2-pyridyl)pyrazol-1-ylmethyl]naphthalene, and its two metal complexes, [Cu(L)3](ClO4)2 (1) and [Zn(L)3](ClO4)2(H2O)2 (2), have been synthesized and characterized. The crystal structure of complex 1 was determined by single crystal X-ray diffraction, which crystallized in monoclinic, space group P2(1)/n with unit cell parameters, a = 12.710(4) angstroms, b = 12.135(3) angstroms, c = 33.450(9) angstroms, beta = 93.281(5) degrees and Z = 4. The Cu atom was six-coordinated to N(1), N(2), N(4), N(5), N(7) and N(8) from three L ligands and formed a slightly distorted octahedral geometry. Complexes 1 and 2, and ligand L were subjected to biological tests in vitro using three different cancer cell lines (HL-60, BGC-823 and MDA-MB-435). Complex 1 showed significant cytotoxic activity against three cancer cell lines. The interactions of complexes 1 and 2, and ligand L with calf thymus DNA were then investigated by thermal denaturation, viscosity measurements and spectrophotometric methods. The experimental results indicated that complexes 1 and 2 bound to DNA by intercalative mode via the ligand L. The intrinsic binding constants of complexes 1 and 2, and ligand L with DNA were 1.8 x 10(4), 5.4 x 10(3) and 2.76 x 10(3) M(-1), respectively.
Zhang
Hang
H
National Research Laboratory of Natural and Biomimetic Drugs, Peking University Health Science Center, P.O. Box 261, Beijing 100083, PR China.
Liu
Chun-Sen
CS
Bu
Xian-He
XH
Yang
Ming
M
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity*; D045744:Cell Line, Tumor; D003300:Copper / Q000737:chemistry; D018360:Crystallography, X-Ray; D004247:DNA / Q000378:metabolism*; D006801:Humans; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity*; D011720:Pyrazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity*; D011725:Pyridines / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity*; D015032:Zinc / Q000737:chemistry
C502915:1-(3-(2-pyridyl)pyrazol-1-ylmethyl)naphthalene; D000970:Antineoplastic Agents; D009942:Organometallic Compounds; D011720:Pyrazoles; D011725:Pyridines; C502916:tris(1-(3-(2-pyridyl)pyrazol-1-ylmethyl)naphthalene)copper(II); C502917:tris(1-(3-(2-pyridyl)pyrazol-1-ylmethyl)naphthalene)zinc(II); D003300:Copper; D004247:DNA; D015032:Zinc