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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

2002; Elsevier BV; Volume: 91; Issue: 1 Linguagem: Inglês

10.1016/s0162-0134(02)00369-0

1873-3344

Gaoyi Han, Pin Yang,

Organometallic Compounds Synthesis and Characterization

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, 1H 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 A260, a slight increase in the viscosity of the DNA, and an increase in the melting point of DNA by 2.9 and 1.6 °C, respectively at DNAbase/DrugPor ratios of 60. The binding constants to DNA were 1.35±0.16×107 M−1 (7) and 1.45±0.12×106 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.