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.
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.
Han
Gaoyi
G
Institute of Molecular Science, Shanxi University, Taiyuan 03006, PR China.
Yang
Pin
P
D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology; D004247:DNA / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D008665:Metalloporphyrins / Q000737:chemistry* / Q000494:pharmacology; D015394:Molecular Structure; D009947:Organotin Compounds / Q000737:chemistry* / Q000494:pharmacology; D012995:Solubility; D013050:Spectrometry, Fluorescence; D014407:Tumor Cells, Cultured; D014867:Water
D000970:Antineoplastic Agents; D008665:Metalloporphyrins; D009947:Organotin Compounds; C466578:dibutyltin(IV) porphinate; D014867:Water; C056189:di-n-butyltin; D004247:DNA