ABSTRACT
5-Methyl 2-furfuraldehyde thiosemicarbazone (M5HFTSC) with nickel(II) leads to three types of complexes: [Ni(M5HFTSC)(2)X(2)], [Ni(M5FTSC)(2)] and [Ni(M5FTSC)(2)] x 2DMF. In the first type the ligand remains in thione form, while in the two other, the anionic thiolato form is involved. The species [Ni(M5HFTSC)(2)X(2)] has been characterized spectroscopically. The structures of [Ni(M5FTSC)(2)] x 2DMF and [Ni(M5FTSC)(2)] have been solved using X-ray diffraction. Biological studies of [Ni(M5HFTSC)(2)Cl(2)] have been carried out in vitro for antifungal activity on human pathogenic fungi, Aspergillus fumigatus and Candida albicans, and in vivo for toxicity on mice. The results are compared to those of the ligand, the metal salt and a similar copper complex [Cu(M5HFTSC)Cl(2)].
Subject(s)
Antifungal Agents/chemical synthesis , Antifungal Agents/pharmacology , Furaldehyde/analogs & derivatives , Nickel/pharmacology , Organometallic Compounds/chemical synthesis , Organometallic Compounds/pharmacology , Thiosemicarbazones/chemical synthesis , Thiosemicarbazones/pharmacology , Animals , Antifungal Agents/chemistry , Aspergillus fumigatus/drug effects , Candida albicans/drug effects , Crystallography, X-Ray , Furaldehyde/chemical synthesis , Furaldehyde/chemistry , Furaldehyde/pharmacology , Humans , In Vitro Techniques , Lethal Dose 50 , Ligands , Magnetic Resonance Spectroscopy , Male , Mice , Molecular Structure , Nickel/chemistry , Organometallic Compounds/chemistry , Spectroscopy, Fourier Transform Infrared , Thiosemicarbazones/chemistryABSTRACT
The 2-furfural semicarbazone and thiosemicarbazone copper and cobalt complexes demonstrated potent cytotoxicity against the growth of suspended leukemias and lymphomas as well as human lung MB9812, colon SW480, ovary 1-A9 and HeLa-S3 uterine carcinoma. In L1210 lymphoid leukemia cell the complexes inhibited preferentially DNA synthesis over 60 min at 25 to 100 microM. The copper and cobalt complexes functioned by multiple mechanisms to suppress synthetic steps in nucleic acid metabolism to reduce deoxynucleotide pools for incorporation into DNA. At high concentrations the complexes suppressed human DNA topoisomerase II activity with DNA nicks and DNA fragmentation but they did not alkylate the bases of DNA, cause intercalation between base pairs or cause cross-linking of DNA strands.
Subject(s)
Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/pharmacology , Cobalt/chemistry , Copper/chemistry , DNA, Neoplasm/drug effects , Drug Screening Assays, Antitumor , Enzyme Inhibitors/pharmacology , Furaldehyde/analogs & derivatives , Furaldehyde/chemical synthesis , Furaldehyde/pharmacology , Humans , Semicarbazones/chemical synthesis , Semicarbazones/pharmacology , Spectrophotometry, Ultraviolet , Thiosemicarbazones/chemical synthesis , Thiosemicarbazones/pharmacology , Topoisomerase I Inhibitors , Tumor Cells, CulturedABSTRACT
The human colon adenocarcinoma-derived cell line CaCo-2 was used as a model system to study the effects of copper (II), tetradentate N-alkyl ligand (H2L) and their complex. The stimulatory effect of the complex was obtained with lower concentrations from 10(-7) to 10(-17) mol.L-1, while inhibiting effects occur from 10(-4) to 10(-6) mol.L-1. According to this study, copper (II) and free ligand were toxic for cultured cells. Our data suggested that the complex, according to our toxicity assays in mice, could be used as an antimitotic agent.
Subject(s)
Caco-2 Cells/drug effects , Copper/pharmacology , Animals , Copper/toxicity , Cyclic N-Oxides/chemistry , Cyclic N-Oxides/pharmacology , Drug Screening Assays, Antitumor , Humans , Male , Mice , Organometallic Compounds/pharmacology , Organometallic Compounds/toxicityABSTRACT
Vitamin D3 (LH) complexes with manganese(II), iron(II), iron(III) and zinc(II) were identified in water-ethanol medium (30/70). Their stability constants were determined at 298 K and at a constant ionic strength of 0.100 M using potentiometric methods. The computerisation of the experimental data showed the presence of ML (M = metal, L = deprotonated vitamin D3) and ML2 species in all cases; in addition, the ML3 iron(III) complex was detected. The calculated overall stability constants beta for MnIIL, FeIIL, FeIIIL and ZnIIL are, respectively, in logarithms, 12.4, 16.5, 28.5 and 16.5. Under the experimental conditions, the only protonated species MLH detected was with iron(III).
Subject(s)
Cholecalciferol/chemistry , Organometallic Compounds/chemistry , Ethanol , Iron/chemistry , Manganese/chemistry , Potentiometry , Solutions , Water , Zinc/chemistryABSTRACT
1. The effects of 24R,25-dihydroxyvitamin D3 [24,25(OH)2D3] on alkaline phosphatase activity (ALP) were evaluated in pig kidney LLC-PK1 cells in culture. 2. The vitamin D3 metabolite increased ALP activity in these cells, whereas no effect of the hormone was observed on gamma-glutamyltranspeptidase and acid phosphatase activities. 3. ALP activity was stimulated after 3- to 12-hr incubation in the presence of 10(-9) mol/l 24,25(OH)2D3 with a maximum after 6 hr. 4. The hormonal induction of ALP activity was prevented by pretreatment of cells by actinomycin D. 5. It is proposed that 24,25(OH)2D3 could increase ALP activity by de novo protein synthesis.
Subject(s)
24,25-Dihydroxyvitamin D 3/pharmacology , Alkaline Phosphatase/metabolism , Kidney Tubules, Proximal/drug effects , Acid Phosphatase/biosynthesis , Acid Phosphatase/metabolism , Alkaline Phosphatase/biosynthesis , Animals , Cell Membrane/drug effects , Cell Membrane/enzymology , Enzyme Activation , Enzyme Induction , Epithelial Cells/enzymology , Hormones/pharmacology , Kidney Tubules, Proximal/enzymology , LLC-PK1 Cells , Microvilli/drug effects , Microvilli/enzymology , Rats , Swine , gamma-Glutamyltransferase/biosynthesis , gamma-Glutamyltransferase/metabolismABSTRACT
gamma-Glutamyl transpeptidase (gamma-GT), primarily described as a kidney enzyme, is also expressed in several cell types of the central nervous system (CNS). It is involved in the glutathione cycle and in cysteine transport. Here we report that the specific activity of this enzyme is transiently increased in the rat brain, following a treatment with 1,25-dihydroxyvitamin D3 (1,25-D3), the active form of vitamin D. In vitro experiments showed that this positive regulatory effect does not affect endothelial cells of the brain microvessels, but does affect pericytes and parenchymal astrocytes. Changes in the specific activity of gamma-GT were not correlated with any important modification of brain amino acid concentrations. Since gamma-GT is though to participate in the scavenging of reactive oxygen species, these data suggest that 1,25-D3 could be an effector controlling detoxification processes in the brain.
Subject(s)
Brain/enzymology , Calcitriol/pharmacology , gamma-Glutamyltransferase/metabolism , Amino Acids/metabolism , Animals , Astrocytes/enzymology , Brain/blood supply , Brain/metabolism , Endothelium, Vascular/enzymology , Endothelium, Vascular/metabolism , Female , Rats , Rats, Sprague-DawleyABSTRACT
The effects of 24R,25-dihydroxycholecalciferol [24,25(OH)2 CC] on alkaline phosphatase (APA), gamma-glutamyltransferase (gamma-GT) and acid phosphatase (AP) activities were investigated on renal cortex slices of intact rats killed at 18h00 or at 06h00. At 06h00, three, six and nine hours after a single intraperitoneal injection of 24,25(OH)2 CC, APA activity was increased by 30%, 51% and 29%, respectively and gamma-GT activity, by 25%, 39% and 38%, as compared to their controls. AP on the other hand was not modified at all. These enzymatic stimulations were statistically higher than those measured at 18h00, respectively APA: 11%, 25%, 28% and gamma-GT: 2%, 20%, 22%. They can be explained by variations in new protein synthesis in relation with rat activity periods. Physiological significance of these renal effects remains to be elaborated.
