pyridoxal-thiosemicarbazone and Leukemia--Erythroblastic--Acute

The complexes [SnR2(L)] (R = Me, Et, Bu, Ph; H2L = pyridoxal thiosemicarbazone) have been prepared and characterized. In the light of the spectral properties of the complexes in the solid state (IR, mass, Mössbauer) the bideprotonated thiosemicarbazonato anion is O(phenolic)-, N(3)-, S-bonded to the tin atom which probably has trigonal bipyramidal coordination with N(3) atom and R groups occupying equatorial positions. NMR ( 1H, 13C and 119Sn) data in CDCl3 or DMSO-d6 suggest that this coordinative picture remains in these solutions. The ethyl, butyl and phenyl derivatives suppress proliferation of Friend erithroleukaemia cells (FLC). Of the pyridoxal thiosemicarbazone complexes so far evaluated. [SnBu2(L)] and [SnPh2(L)] showed the lowest thresholds for inhibition of FLC proliferation. The effects of these compounds on DMSO-induced differentiation of FLC, DNA synthesis and reverse transcriptase were also assayed.

Topics: Animals; Antineoplastic Agents; Cell Differentiation; Cell Division; Dimethyl Sulfoxide; DNA, Neoplasm; Friend murine leukemia virus; Leukemia, Erythroblastic, Acute; Magnetic Resonance Spectroscopy; Mass Spectrometry; Mice; Organotin Compounds; Pyridoxal; Reverse Transcriptase Inhibitors; Spectroscopy, Mossbauer; Thiosemicarbazones; Tumor Cells, Cultured

Thiosemicarbazones are a wide group of organic derivatives whose biological activities are a function of the parent aldehyde or ketone and of the coordination metal type. Some thiosemicarbazones possess a broad spectrum of potentially useful chemotherapeutic properties (antitumor, antibacterial, antiviral, antimalarial). The present study reports the biological effects of pyridoxal thiosemicarbazone, H2L, and relative complexes with copper, [(Cu(HL)(OH2))2]++ and with cobalt, [Co(III)(L)(HL)] on the differentiation of Friend erythroleukemia cells (FLC). They are murine proerythroblasts chronically infected by a producing Friend leukemia virus complex; their exposure to dimethylsulfoxide (Me2SO) or other chemical agents induces these cells to terminal erythroid differentiation, therefore these cells represent a good model of differentiation in vitro. Here we describe induction differentiation experiment of pyridoxal thiosemicarbazone and relative complexes of copper and cobalt on FLC performed with concentrations of 50 ug/ml (ligand), 2 ug/ml (complexes). These have little effects on cell proliferation at doses used in these experiments. Higher doses have evident cytotoxic effects. The treatment with the copper complex induces a moderate differentiation of FLC and enhances effects on erythroid differentiation of Me2SO-induced FLC. On the contrary H2L and [Co(III)(L)(HL)] haven't inducing effects or enhancing effects on Me2SO-induced FLC hemopoietic differentiation. In conclusion, the present study shows that copper complexes of pyridoxal thiosemicarbazone exert action of inducing agent and are able to enhance Me2SO-induced FLC hemopoietic differentiation.

Topics: Animals; Cell Differentiation; Erythropoiesis; Friend murine leukemia virus; Hematopoiesis; Leukemia, Erythroblastic, Acute; Mice; Pyridoxal; Stimulation, Chemical; Thiosemicarbazones; Tumor Cells, Cultured