Antiproliferative action of isatine-beta-thiocarbohydrazone and N-ethylisatine-beta-thiocarbohydrazone on human PBMC and on two neoplastic cell lines.

The antiproliferative action of two synthetic compounds, isatine-b-thiocarbohydrazone (IsTCH) and N-ethyl isatine-beta-thiocarbohydrazone (N-Et-IsTCH), towards healthy human peripheral blood mononuclear cells (PBMC) and two neoplastic cell lines in vitro, was investigated. IsTCH and N-Et-IsTCH were dissolved in DMSO and then diluted with nutrient medium to desired final concentration. Target cells were PBMC, as well as human cervix carcinoma - HeLa cells, and murine melanoma B16 cells. Five different concentrations (3 microM to 50 microM) of investigated agents were applied on target cells. Cell survival was determined 72 h after the agent's action using MTT test. Results obtained showed that both investigated compounds exerted a dose dependent antiproliferative action to neoplastic cell lines. Their action was only cytostatic; trypan blue exclusion test did not show any sign of direct drug cytotoxicity when drugs concentration were less than 50 microM. ICs50 +/- SD for IsTCH antiproliferative action were 61.69 +/- 4.25 microM for HeLa cells; 34.1 +/- 7.15 microM for B16 cells: 17.62 +/- 7.11 microM for nonstimulated and 30.0 +/- 9.46 microM for stimulated (by 5 mg/ml PHA) PBMC. ICs50 +/- SD for the action of N-Et-IsTCH were 21.86 +/- 1.77 microM for HeLa cells; 10.37 +/- 1.55 microM for B16 cells; >47 microM for both, nonstimulated and for stimulated, PBMC. Nonstimulated human PBMC appeared to be the most sensitive to the cytostatic IsTCH action; while HeLa cells were the most resistant. N-Et-IsTCH showed more than two or five fold stronger antiproliferative effect toward B16 cells than on HeLa or PBMC cells, respectively, and more than three times intensive activity compared to IsTCH, indicating specificity of N-Et-IsTCH towards inhibition of melanoma cell growth. While increasing concentrations of IsTCH led to decrease in the the PBMC induced suppression of HeLa cell survival; N-Et-Is-TCH in the difference from IsTCH, in dose dependent way contributed to the PBMC induced suppression of HeLa cell survival. In conclusion, the activity of N-Et-Istch on malignant melanoma cells deserves further investigation.

T-2 toxin affects proliferation of three different neoplastic cell lines.

The antiproliferative effect of T-2 toxin (T-2) towards mouse melanoma B16 cells, human myelogenous leukemia K562 cells, and human cervix carcinoma, HeLa cells, was studied. For the first four days of T-2 presence B16 cell survival was decreased in dose dependent fashion. However, cell survival after eleven days T-2 action may be dual: some stimulation of cell growth that was direct function of the number of seeded cells per well was observed and cell survival (for the highest number of seeded cells) six times greater than control, was noticed at 20 nM T-2 toxin concentration. A smaller cell growth stimulation (cell survival more than 3 times higher than control) was observed with a lower cell number seeded per well. Nevertheless, by eleventh day concentrations of T-2 higher than 35 nM completely inhibited B16 cell proliferation. The same trend was noticed for T-2 action towards K562 cells. Treatment of HeLa cells with various T-2 concentrations led to a marked inhibition of cell survival that was more pronounced at the end of 44th or 72nd hour, than after the 20th hour of agent's action. ICs50 values obtained in the present work, suggest that B16 cells were the most sensitive to T-2 antiproliferative action, while HeLa cells were the most resistant. When PBMC were cultured with HeLa cells the antagonism against various T-2 concentrations was observed; cell survival determined after 44, or 72 hours of cells incubation, was less decreased compared to cultures treated with T-2, or with PBMC only. In addition, it was shown that T-2 and cis-DDP had an antagonist effect on HeLa cells survival.

Peroxo heteroligand vanadates(V): synthesis, spectra-structure relationships, and stability toward decomposition.

Effect of heteroligands (L) on the properties of vanadium peroxides was investigated by preparing a number of peroxovanadium complexes, which were characterized by analysis, IR, UV/V and NMR spectra. X-ray structures for some were obtained. The vanadates(V) contain the cation M(I) = Na, K, NH4, Rb or Cs. Diperoxo complexes include M(I)[VO(O2)2 L], where L = dipyridyl, o-phenanthroline; M(I)3[VO(O2)2(C2O4)]; K2[(nicotinic acid)[VO(O2)2]2]H2O;M(I)4[O[VO(O2)2]2cystine]2H2O; H4[O[VO(O2)2(adenine)2)2]2H2O; and K2H2[O[VO(O2)2(adenosine)]2] 2H2O. Monoperoxo vanadates(V) correspond to the formula M(I)2[VO(O2)L]2 for L = citrate and malate; M(I)2[VO(O2)L] for L = nitrilotriacetate; M(I)[VO(O2)L] for L = iminodiacetate, tartrate and EDTA; and [HVO2(O2)(adenosine)]2H2O. Syntheses of these heteroligand peroxovanadium compounds are sensitive to pH, temperature and the concentration of the components. The stability towards decomposition in solid state, mother-liquid and pure water solutions depends upon the heteroligand. Characteristic (V = O) and (O-O) stretching frequency bands in IR can be correlated with the corresponding bond lengths and the [peroxo approximately V(V)] charge transfer bands in UV/V spectra. Intramolecular one-electron transfer in peroxo vanadates(V) can trigger the generation of radicals, and its dependency upon the nature of the heteroligand is discussed.