Synthesis and characterization of water-insoluble and water-soluble dibutyltin(IV) porphinate complexes based on the tris(pyridinyl)porphyrin moiety, their anti-tumor activity in vitro and interaction with DNA.

Abstract

The water-insoluble and water-soluble organotin(IV)porphinate complexes based on the tris-(4-pyridinyl)porphyrin and tris(N-methyl-4-pyridiniumyl)porphyrin moieties were synthesized and characterized by elemental analysis, (1)H NMR, IR and electrospray ionization mass spectra. The in vitro activity of the compounds against P388 leukemia and A-549 was determined. The results show that the anti-tumor activities of organotin(IV)porphinate is related to the water solubility of the compounds and the central ion in the porphyrin ring. The interaction between the water-soluble dibutyltin(IV) porphinate (7 and 10) complexes and DNA has been investigated. The result shows that compounds 7 and 10 cause DNA hypochromism measured by A(260), a slight increase in the viscosity of the DNA, and an increase in the melting point of DNA by 2.9 and 1.6 degrees C, respectively at DNA(base)/Drug(Por) ratios of 60. The binding constants to DNA were 1.35+/-0.16 x 10(7) M(-1) (7) and 1.45+/-0.12 x 10(6) M(-1) (10) determined using EB competition method based on the porphyrin concentration, which is 20 and five times greater than that of precursor porphyrins [5-p,o-(carboxy)methoxyphenyl-10,15,20-tris(N-methyl-4-pyridiniumyl)] porphyrin (p,o-tMPyPac) to DNA. Electrophoresis test shows that the compounds cannot cleave the DNA. According to the electrophoresis test result and all the above results, the cytotoxic activity against P388 and A-549 tumor cells appears not to come from the cleavage of DNA caused by the compounds but from the high affinity of compounds to DNA.

• Authors: Gaoyi Han, Pin Yang
• Journal: Journal of inorganic biochemistry (J Inorg Biochem) Vol. 91 Issue 1 Pg. 230-6 (Jul 25 2002) ISSN: 0162-0134 [Print] United States
• PMID: 12121780 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Metalloporphyrins
• Organotin Compounds
• dibutyltin(IV) porphinate
• Water
• di-n-butyltin
• DNA

Topics

• Antineoplastic Agents (chemistry, pharmacology)
• DNA (chemistry, metabolism)
• Humans
• Metalloporphyrins (chemistry, pharmacology)
• Molecular Structure
• Organotin Compounds (chemistry, pharmacology)
• Solubility
• Spectrometry, Fluorescence
• Tumor Cells, Cultured
• Water