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It was shown in chronic experiments on dogs that denervation of the kidneys does not eliminate the stimulant action of furosemid, etacrinic acid and novurit. Stoppage of the urine flow in dogs with a denervated single kidney did not lead to a complete removal of the stimulant effect of the diuretics on renin secretion.
In experiments in vivo the mercuric diuretic, novurite, and ethacrynic acid in therapeutic doses (25 and 50 mg/kg, respectively) do not block the respiration and active transport of calcium in the kidney mitochondria. The diuretic effect of these substances is not prevented by cystein (50 mg/kg), the donator of sulphydryl groups. In vitro novurite (3 mM) and ethacrynic acid (1 mM) block the systems of ionic transport inthe kidney epithelium cells and in concentrations of 0.2 and 0.5 mM, respectively, disturb the oxygen uptake and oxidative phosphorylation in the kidney mitochondria. A preliminary administration of cystein (5 mM) into the incubation medium prevents these effects. Novurite and ethacrynic acid manifest the typical thyol toxins of general cell effect in doses considerably exceeding the therapeutic ones. A specific "kidneys" effect of these substances is not connected with their ability to block SH-group of biologically active substances.
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2,6-Bis(benzimidazol-2-yl)pyridine (L) ligand and complexes [M(L)Cl(2)] and [Fe(L)(2)](ClO(4))(2) (M=Zn, Cd, Hg) have been synthesized. The geometries of the [M(L)Cl(2)] complexes were derived from theoretical calculation in DGauss/DFT level (DZVP basis set) on CACHE. The central M(II) ion is penta-coordinated and surrounded by N(3)Cl(2) environment, adopting a distorted trigonal bipyramidal geometry. The ligand is tridentate, via three nitrogen atoms to metal centre and two chloride ions lie on each side of the distorted benzimidazole ring. In the [Fe(L)(2)](ClO(4))(2) complex, the central Fe(II) ion is surrounded by two (3N) units, adopting a octahedral geometry. The elemental analysis, molecular conductivity, FT-Raman, FT-IR (mid-, far-IR), (1)H, and (13)C NMR were reported. The antimicrobial activities of the free ligand, its hydrochloride salt, and the complexes were evaluated using the disk diffusion method in dimethyl sulfoxide (DMSO) as well as the minimal inhibitory concentration (MIC) dilution method, against 10 bacteria and the results compared with that for gentamycin. Antifungal activities were reported for Candida albicans, Kluyveromyces fragilis, Rhodotorula rubra, Debaryomyces hansenii, Hanseniaspora guilliermondii, and the results were referenced against nystatin, ketaconazole, and clotrimazole antifungal agents. In most cases, the compounds tested showed broad-spectrum (Gram positive and Gram negative bacteria) activities that were either more effective than or as potent as the references. The binding of two most biologically effective compounds of zinc and mercury to calf thymus DNA has also been investigated by absorption spectra.
The effect of diuretics on tryptophan fluorescence of blood serum proteins divided by electrophoresis was studied. It was shown that ethacrynic acid produces the most significant extinction of tryptophan fluorescence in albumin fraction and novurit in globulin fraction. Furosemide possessing a high affinity for all three obtained fractions of protein does not exhibit a preferential binding to one or another of these fractions. It was also found that furosemide and ethacrynic acid by binding to human serum albumin molecule produce its conformational alterations. Mercury diuretic does not possess such effect.
The effect of several diuretic agents on thoracic duct and right lymph trunk lymph flow, and on some other parameters was examined in normal dogs and dogs with ascites produced by the constriction of inferior cava vein. In normal animals furosemide and etacrynic acid in diuretic doses did not influence thoracic duct lymph flow and reduced slightly arterial pressure and GFR (creatinine clearance). Hydrochlorothiazide increased slightly thoracic duct flow. Neither of the drugs had any significant influence on right trunk lymph flow. In dogs with ascites all drugs tested (furosemide, etacrynic acid and mercurophylline) reduced lymph flow in the thoracic duct but had no effect on the flow in the right trunk. The drugs reduced markedly arterial and inferior cava venous pressure. It is concluded that their effect on ascites is not based on enhanced lymphatic absorption and transport but mainly on the reduction of fluid and protein leakage from the liver sinusoids.
The effect of novurit, mannitol and furosemide on permeability of the intercellular interstice of the frog urinary bladder by inulin, saccharose, iodide, lithium cation and fluorescein moving against a concentration gradient was examined. Novurit (0.5--6 mM/l) raised permeability of the intercellular interstice by all test substances and ions. Mannitol (210 mM/l) increased permeability of the intercellular interstice by lithium cation and fluorescein, while furosemide failed to exert any effect on permeability. The character of asymmetrical ionic flows moving in opposite directions across the wall of the frog urinary bladder is discussed.
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Mercury, diazonium ions and dyes which bind nucleic acids were covalently linked to dextrans using methods that resulted in non-hydrolyzable reagent-dextran bonds without impairing the binding abilities of the reagents, i.e. these dextran derivatives reacted with thiols, phenols/imidazoles and nucleic acids respectively. Since these dextran derivatives cannot penetrate into cells and since dextran itself does not bind to cells, these compounds represent reagents specific for the cell surface. They may be used both to evaluate cell surface constituents of intact cells and to affect viable cells via an interaction with those constituents. Mercury-dextran was found to bind to cells; the amount of mercury thus attached to the cells was about ten times smaller than when an equivalent concentration of free mercury ions was used. Mercury-dextran, bound to cells after a 30-min exposure at room temperature, was localized on the surface of these cells, as sodium borohydride reduced this complex giving rise to the intact cells, elementary mercury and free dextran which was released into medium. When cells were constantly exposed to the mercury-dextran, its toxic effects were comparable to that of free mercury ions. Diazonium-dextran, which also binds tightly to the cell surface, was also considerably toxic. Dextrans substituted with dyes which bind to nucleic acids were less toxic than the parent dyes themselves; it was shown that the attachment of such a dye to dextran decreased the binding of dye to cells under detection limits.
The reaction of [PPh4]3[Re7C(CO)21] (1) with 1 or more equiv of Hg(OAc)2 in dichloromethane provides the monomercury derivative [PPh4]2[Re7C(CO)21HgOAc] (2) in high yield. However, in the presence of methanol the reaction of 1 with 2 equiv of Hg(OAc)2 yields the dimercury hexarhenium cluster compound [PPh4]2[Re6C(CO)18(HgOAc)2] (3) together with the dirhenium complex [PPh4][Re2(CO)6(mu-OMe)2(mu-OAc)] (4). The dimercury compound 3 reacts with various thiols HS-Z to form thiolate-substituted derivatives [PPh4]2[Re6C(CO)18(HgSZ)2] [Z = C6H4Br (5); C5H4N (6); C2H4COOH (7)]. All new compounds have been characterized by a combination of analytical and spectroscopic data, and the molecular structures of compounds 3-6 have been determined by X-ray crystallography.
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The combination of HgF2 and 2-aminoethanethiol (AET, with some AET.HCl present) yielded a cyclic tetranuclear thiolate, [Hg4Cl4(SCH2CH2NH2)4] (1), with alternating Hg and S atoms. The Cl from the reaction mixture led to the formation of Hg-Cl bonds with no Hg-F in the final product. In contrast, a similar reaction with HgBr2 yielded a nonanuclear cluster, [Hg9Br15(SCH2CH2NH3)15]3+ (2), and the disulfide salt {[HgBr4][(NH3CH2CH2S-)2]} (3). Despite similar reactions, the AET groups in 2 are protonated compared to the nonprotonated amine groups in 1, which allows the ligand to chelate the Hg atom in the latter compound. The reaction with HgI2 yielded a cyclic tetranuclear compound, [Hg4I6(SCH2CH2NH2)2(SCH2CH2NH3)2](H2O/EtOH) (4), containing protonated and nonprotonated AET groups. Compound 4 at room temperature irreversibly rearranges to [Hg4I4(SCH2CH2NH2)4] (5), which is isostructural to 1. A systematic pathway for the formation of 1 along with the intramolecular conversion of 4 to 5 is proposed. These compounds demonstrate that very diverse Hg-S compounds form under similar reaction conditions.
The binding of furosemide, novurit and ethacrynic acid with human serum albumin, phospholipid liposomes, mitochondria and plasmatic membranes of rat kidneys was studied by the fluorescent probe 1-anilino naphthalene-8-sulfonate (1,8-ANS) method. It is shown that ethacrynic acid has high associative constants with serum albumin molecule and plasmatic membranes. Novurit has the greatest affinity with rat kidney mitochondria. Furosemide does not bind with plasmatic membranes and has very low constants of association with mitochondria and phospholipid liposomes.