Selective guanosine binding and cytotoxicity of a benzimidazole derived dinickel complex.
A water-soluble dinickel(II) complex of ethylene glycol-bis(beta-aminoethyl ether) N,N,N',N'-tetrakis(2-benzimidazoyl) (EGTB) was synthesized and fully characterized. The complex crystallizes in a monoclinic system with space group P2(1)/c, a=10.125(1)A, b=28.393(3)A, c=11.026(1)A, and beta=98.966(2) degrees. The hexa-coordinated nickel(II) centers in the centrosymmetric complex adopt a distorted octahedron geometry. The complex binds to purine nucleotides covalently and shows a clear preference for guanosine-5'-monophosphate (5'-GMP) over adenosine-5'-monophosphate (5'-AMP). Its binding to calf thymus DNA (CT-DNA) induces a remarkable conformational variation. The cytotoxic activity of the complex was tested against diverse cell lines including human leukemic cell line U937, macrophage cell line Raw 264.7, human cervical cancer cell line Hela, and human hepatocytes cell line L02. The complex shows a significant inhibition against U937 and Raw 264.7 but little inhibition against Hela and L02.
Chen
Zhanfen
Z
State Key Laboratory of Coordination Chemistry, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210093, PR China.
Wang
Xiaoyong
X
Zhu
Yangguang
Y
Li
Yizhi
Y
Guo
Zijian
Z
D000818:Animals; D001562:Benzimidazoles / Q000737:chemistry*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002942:Circular Dichroism; D018360:Crystallography, X-Ray; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D006151:Guanosine / Q000737:chemistry* / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D015394:Molecular Structure; D009532:Nickel / Q000737:chemistry* / Q000378:metabolism; D009942:Organometallic Compounds / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D020298:U937 Cells
D001562:Benzimidazoles; D009942:Organometallic Compounds; D006151:Guanosine; D009532:Nickel; D004247:DNA; C427203:calf thymus DNA; C031000:benzimidazole