Manganese(II) complex of 6,7-dicycanodipyridoquinoxaline with antitumor activities: synthesis, crystal structure and binding with DNA

J Inorg Biochem. 2002 Nov 25;92(3-4):149-55. doi: 10.1016/s0162-0134(02)00569-x.

Abstract

A new Mn(II) complex with the planar ligand 6,7-dicycanodipyrido[2,2-D:2',3'-f]quinoxaline (L) [MnL(NO(3))(H(2)O)(3)]NO(3).CH(3)OH (1) has been synthesized and characterized by elemental analysis, IR, TG-DTA and molar conductance. Its crystal structure was determined by X-ray diffraction, crystal data: yellow, triclinic, space group P1;, Z=2, a=7.3743(8) A, b=11.2487(15) A, c=14.1655(15) A, alpha=79.412(2) degrees, beta=83.208(2) degrees, gamma=80.466(2) degrees. The Mn atom was hexa-coordinated to form a distorted octahedral geometry by two nitrogen atoms of L and four oxygen atoms of three H(2)O and NO(3)(-) in the complex. The binding mode of the complex with calf thymus DNA has also been investigated with spectrophotometric methods, viscosity and thermal denaturation measurements. The experimental results indicate that the complex intercalated into DNA base pairs via the ligand L. The intrinsic binding constant K(b) values for 1 (5.00 x 10(5) M(-1)) and L (1.65 x 10(5) M(-1)) were determined by absorption titration and calculated with the model of McGhee and Von Hippel. Biological tests against four different cell lines (HL-60, KB, Hela and BGC-823) in vitro showed that the complex had significant antitumor properties since the 50% inhibition concentrations (IC(50)) of the complex were within a microM range similar to those of antitumor drug 5-fluorouracil.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Binding Sites
  • Cell Division / drug effects
  • Crystallography, X-Ray
  • DNA / chemistry*
  • DNA / metabolism
  • Humans
  • Intercalating Agents
  • Manganese / chemistry
  • Molecular Structure
  • Nucleic Acid Conformation / drug effects
  • Organometallic Compounds / chemical synthesis
  • Organometallic Compounds / chemistry
  • Organometallic Compounds / pharmacology*
  • Quinoxalines / chemical synthesis
  • Quinoxalines / chemistry
  • Quinoxalines / pharmacology
  • Tumor Cells, Cultured

Substances

  • 6,7-dicycanodipyridoquinoxaline manganese(II) complex
  • Antineoplastic Agents
  • Intercalating Agents
  • Organometallic Compounds
  • Quinoxalines
  • Manganese
  • DNA
  • calf thymus DNA