Ruthenium complexes, preparation method thereof and application

A ruthenium complex and complex technology, applied in the field of preparation of ruthenium polypyridine complexes, can solve the problems of increased cell drug resistance and achieve the effect of solving the problem of cell drug resistance

Inactive Publication Date: 2013-02-27
SUN YAT SEN UNIV
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  • Abstract
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  • Claims
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Problems solved by technology

[0004]Although Topo I—camptothecin, CPT (Bioorg. Med. Chem. 2004, 12, 1585) or Topo II— Anticancer drugs targeting Etoposide, VP-16 (Curr. Med. Chem. 2005, 5, 363) have been successfully used clinically, but single topoisomerase Targeted anticancer drugs have many defects

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  • Ruthenium complexes, preparation method thereof and application
  • Ruthenium complexes, preparation method thereof and application
  • Ruthenium complexes, preparation method thereof and application

Examples

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Embodiment 1

[0032] The preparation method of embodiment 1 ligand and complex

[0033] (1) Ligand 2,4,6-PIPTH; 2,3,4-PIPTH; 2,5-PIPDH; 3,5-PIPDH synthesis method:

[0034] a) The synthetic method of o-phenanthrolene-5,6-diamine:

[0035] The synthesis of o-phenanthrolene-5,6-diamine is according to ( Tetrahedron Letters , 2006, 38, 8159) Method: Dissolve 4.2g of phenanthroline-5,6-dione in 200mL of absolute ethanol, and add 4.8g of hydroxylamine hydrochloride and 5.9g of BaCO 3 , refluxed at 80°C for 12 hours, then rotary evaporated to remove the solvent, the obtained solid was dissolved with dilute HCl and the pH was adjusted to about 6, stirred for half an hour, a green solid precipitated, filtered, washed, dried and dissolved in 300mL of absolute ethanol, added 4.0 g10% palladium carbon, under the protection of Ar, start to add N dropwise after refluxing at 80°C 2 h 4 ·H 2 The mixed solution of O and ethanol (35mL / 150mL) was dropped within 1 hour and continued to pass Ar to refl...

Embodiment 2

[0055] Example 2 CD spectral analysis

[0056] In circular light, when a beam of polarized light passes through an optically active medium, there will be a phase difference between the left-handed and right-handed circular vibration components, which is the basic principle of circular dichroism. The symmetry of the chiral complexes can be obtained according to the changes in the CD spectra of the resolved isomers. The ruthenium complex of fixed concentration 10 μ M is analyzed its CD spectrum under the wavelength of 200-700nm ( Figure 4 ).

Embodiment 3

[0057] Example 3 Topoisomerase Inhibition Experiment of Ru(II) Complexes

[0058] Inhibition ability was judged according to the method of drug inhibition topoisomerase unwinding experiment. The compound was reacted with pBR322 DNA and topoisomerase in an appropriate buffer, and the reaction mixture was incubated at 37 °C for a certain period of time, and then the reaction termination solution was added to terminate the reaction. On 0.9% agar enamel (TBE) gel, electrophoresis under constant voltage conditions of 80 V. The gel was stained with 1.5 μg / mL EB solution and photographed under UV light. The complex concentration that inhibits 50% of Topo I or Topo II activity is defined as IC 50 . The experimental results show that the complex is a dual inhibitor of Topo I and Topo II, showing a very good inhibitory ability, IC 50 The value is about 3~5 mM ( Figure 5 ). And all the complexes are superior to the reported small organic molecule inhibitors in terms of water so...

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Abstract

The invention discloses a novel dual inhibitor of deoxyribonucleic acid (DNA) topoisomerase I and DNA topoisomerase II. Mononuclear ruthenium (II) complexes containing a plurality of hydroxy ligands are synthesized, the complexes are stable in structure, the water-solubility of the complexes is better than that of normal organic small molecule inhibitors, and the complexes have dual poison effect for I type DNA topoisomerase and II type DNA topoisomerase and can inhibit body cancer cell growth obviously.

Description

technical field [0001] The invention relates to the fields of topoisomerase I / II and anticancer drugs, in particular to a preparation method and application of a novel ruthenium polypyridine complex. Background technique [0002] DNA, as the carrier of genetic information, plays an important role throughout life. Intracellular DNA exists in an astonishing supercoiled form, and the DNA double helix chain must constantly switch between the complex supercoiled state and the unwinding state. The normal progress of all processes is inseparable from a ribozyme —DNA topoisomerase (Topoisomerase, Topo) ( Cancer Treatment Reviews 1994, 20, 73). DNA topoisomerase maintains the stability of the cell genome through gene recombination, cell cycle checkpoints, DNA repair and other signaling pathways, and it is essential for the normal proliferation of cells. However, when its activity is overexpressed, it will have a negative impact on cells and even cause gene mutations ( Nat. Rev...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07F15/00A61P35/00
Inventor 巢晖张平玉计亮年
Owner SUN YAT SEN UNIV
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