Synthesis, Spectroscopic Analysis and Assessment of the Biological Activity of New Hydrazine and Hydrazide Derivatives of 3-Formylchromone.

The hydrazine and hydrazide derivatives of benzo-γ-pyrones with fluorine substituents remain an unexplored group of chemical compounds. This preliminary study reports the synthesis, structural assessment, initial microbiological screening and biological testing of the synthesized compounds on cell lines using the XTT-assay. A series of 10 novel hydrazine and hydrazide derivatives of 3-formylchromone were synthesized and their structures determined. Structural assessment consisted of elemental analysis, IR, ¹H-NMR, 13C-NMR, MS and crystallographic studies. Antimicrobial activity was tested on standard strains representing different groups of microorganisms. The tested compounds were found to inhibit microbial growth. Concentrations of 0.01⁻1250 µmol/L were found to influence cell proliferation, demonstrating antiproliferative and stimulation of proliferation against two cell lines: the L929 cell line (mouse fibroblast cell line) and the EA.hy926 cell line (the human umbilical vein, somatic cell hybrid).

Fibrinogen, bFGF and VEGF levels during antibiotic therapy in gynecologic cancer: a preliminary report.

The role of angiogenesis in the development of neoplasia has been identified and characterized. However, antiangiogenic therapeutic intervention still requires more evidence to become recognized and successful. The aim of this study was to evaluate levels of selected proangiogenic factors, such as fibrinogen, vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in serum of patients with the gynecologic cancer on the first, third and sixth day of antibiotic therapy, routinely administered as a perioperative treatment. In addition, serum concentrations of gamma-gamma dimers and alpha-polymers of cross-linked fibrin structure and the degree of bFGF binding with the fibrin network were investigated. Immunohistochemistry staining of the excised tumor tissue was also performed. We observed higher levels of bFGF, VEGF, as well as fibrinogen in patients with gynecologic malignancy, as compared to healthy women. In cancer patients, the concentration of alpha-polymers and gamma-gamma dimers of fibrin network increased. Further only gamma-gamma dimers fraction of fibrin was found to bind to bFGF. Immunohistochemical analysis indicated the presence of bFGF in an excised tumor tissue. In conclusion, the decrease of proangiogenic bFGF and fibrinogen levels in a clinical trial of gynecologic patients may confirm anti-angiogenic properties of selected antibiotic therapy.

Effect of phosphorohydrazone derivatives of chromone on fibrin polymerization in the presence of bFGF.

The effect of ten phosphorohydrazone derivatives of chromone on the fibrin formation process was evaluated in the presence of basic fibroblast growth factor (bFGF), which plays an important role in tumor angiogenesis. The relationship between the chemical properties of the derivatives and the resulting fibrin structure was also examined. The structure of fibrin was analyzed by UV spectrophotometry and the degree of bFGF binding to fibrin was estimated by Western blotting. The measurements were taken at 3 different pH values: 6.64, 7.60 and 8.40. Three of the analyzed phosphorohydrazone derivatives (compounds 2, 7 and 10) demonstrated the most significant influence on reduction of polymerization at the studied pH values.

Influence of phosphorohydrazone derivatives of benzopyrones on polymerization and viscosity of fibrin.

The synthesis and antitumour and antibacterial activity of coumarin and chromone phosphorohydrazones have been reported. This study describes influence of phosphorohydrazones derivatives of coumarin and chromone on the polymerization and viscosity of fibrin. The fibrin polymerization assay was performed by the Shen and Lorand method and the clot viscosity was measured on the basis of Shen and Lorand and Marchi and coworkers methods. Among the eight compounds tested, one coumarin derivative and two chromone derivatives showed significant activity.

The effect of hydrazine derivatives of 3-formylchromones on angiogenic basic fibroblast growth factor and fibroblast growth factor receptor-1 in human melanoma cell line WM-115.

The hydrazine derivatives of benzopyrones remain an unexplored group of chemical compounds. This preliminary study investigates the influence of A-5, CH-3 and K-2 derivatives at concentrations of 1, 10, 100 nM and 1 µM on selected biochemical factors of a melanoma cell line WM-115, with regard to their potential angiogenic properties. The studied compounds were found to influence cell proliferation, as well as total protein, bFGF and FGFR1 concentration.

The effect of cadmium on the coagulation and fibrinolytic system in women with uterine endometrial cancer and myoma.

OBJECTIVES: Cadmium (Cd) is a persistent and widespread environmental pollutant, which may constitute a potential risk factor for hormone-dependent tumors such as endometrial cancer. The vascular endothelium is an important target of cadmium toxicity, which may interfere with the coagulation cascade and fibrinolytic system. The aim of this research was to investigate whether in female patients with uterine endometrial cancer or myoma in comparison to healthy women, the concentration of cadmium in blood affects the process of coagulation and fibrinolysis. MATERIALS AND METHODS: The study group comprised 91 women: 35 healthy (A-control), 39 with uterine myoma (B) and 17 with endometrial cancer (C), in which blood cadmium concentrations (BCd), coagulation and selected fibrinolysis parameters in plasma were assayed. RESULTS: In the women with myoma and especially in those with endometrial cancer disturbances in coagulation and fibrinolysis were detected when compared to the healthy women. In the group of women with endometrial cancer significant changes in prothrombin index, levels of fibrinogen, fibrin D-dimer and t-PA were observed. Whereas, in the patients with myoma significant changes in prothrombin time, index of vWillebrand Factor and fibrin D-dimer level were noted. Mean BCd concentrations in subsequent groups were as follows: B - 0.91±0.81; C - 0.78±0.45 µg Cd/l and did not differ significantly in comparison with the control group (0.86±0.35 µg Cd/l). However, in each study group smokers had approximately twice as high BCd as non-smokers. Studies also showed significant associations between BCd and fibrinogen level and thrombin time among the women with myoma and endometrial cancer, as well as in healthy women. Moreover, thrombin time significantly correlated with fibrinogen level in the women studied. CONCLUSIONS: In the patients with myoma and especially in these with endometrial cancer disturbances in coagulation and fibrinolysis parameters leading to hypercoagulability were detected. Exposure to cadmium can be one of the factors inducing these changes.

The influence of chromone based hydrazones on lipid peroxidation and bFGF concentration in the HL-60 cell line.

Natural and synthetic derivatives of benzo-γ-pyrones (i.e. flavones, chromones, and coumarins) and their synthetic analogues possess a wide range of biological properties in vitro and in vivo. In this paper we investigated the influence of two hydrazone compounds of chromones, 3-{[(2-dimethoxytiophosphoryl)-2-methylhydrazono]-methyl}-chromen-4-one (CH-3) and 2-amino-6-chloro-3-[(2-hydroxyethyl)-hydrazonomethyl]-chromen-4-one (A-12), on lipid peroxidation and bFGF concentration in the HL-60 cells. Both of the studied compounds had a significant influence on bFGF and TBARS in ranges -137.20 ~ 380.26% and -81.66 ~ -28.68%, respectively, in comparison with the control (counted as 0%).