Metal-Based Drugs最新文献

Some manganese(II) complexes derived from different sulphadrugs and heterocyclic ketones have been prepared. These complexes have been characterized on the basis of elemental analyses, molecular weight determinations, conductivity measurements, infrared, ESR and magnetic measurements. The spectral data suggest that the ligands act in a monobasic, bidentate manner coordinating through nitrogen atom. A high spin tetrahedral geometry around this metal has been proposed on the basis of magnetic and spectral studies. The isolated products are coloured solids, soluble in DMSO, DMF and MeOH. All the complexes are monomeric in nature as indicated by their molecular weight determinations and conductivity measurements in dry DMF show them to be non-electrolytes. All the ligands and their corresponding complexes have been screened for their fungicidal, bactericidal and nematicidal activities.

Magnesium is an essential element for all living systems. The quantification of free intracellular Mg(2+) concentration ([Mg(2+)](i)) is of utmost importance since changes in its basal value may be an indication of different pathologies due to abnormalities of Mg(2+) metabolism. In this work we used (31)P NMR and fluorescence spectroscopy to determine the resting [Mg(2+)](i) in bovine chromaffin cells, a neuron-like cellular model, as well as confocal laser scanning microscopy to study the free Mg(2+) spatial distribution in these cells. (31)P NMR spectroscopy did not prove to be effective for the determination of [Mg(2+)](i) in this particular case due to some special morphological and physiological properties of this cell type. A basal [Mg(2+)](i) value of 0.551 +/- 0.008 mM was found for these cells using fluorescence spectroscopy and the Mg(2+)-sensitive probe furaptra; this value falls in the concentration range reported in the literature for neurons from different sources. This technique proved to be an accurate and sensitive tool to determine the [Mg(2+)](i).lntraceilular free Mg(2+) seems to be essentially localized in the nucleus and around it, as shown by confocal microscopy with the Mg(2+)-sensitive probe Magnesium Green. It was not possible to derive any conclusion about free Mg(2+) localization inside the chromaffin granules and/or in the cytoplasm due to the lack of sufficient spatial resolution and to probe compartmentalization.

A condensation reaction of 2-amino-1,3,4-thiadiazole with 2-pyrrolecarboxaldehyde to form tridentate NNN donor Schiff base has been performed. The prepared Schiff base was further used for the formation of metal complexes having stoichiometry [M(L)(2)]X(n), where M=Cu(II) or Zn(II), L=N-(2-pyrrolylmethylene)-2-amino-1,3,4-thiadiazole, X=SO(4) (2-), NO(3) (-), C(2)O(4) (2-) or CH(3)CO(2-) and n=1 or 2. The new compounds described here have been characterized by their physical, spectral and analytical data, and have been screened against several bacterial strains such as Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa. The antibacterial potency of the Schiff base increased upon chelation/complexation, having the same metal ion (cation) but different anions opening up a novel approach in finding new ways to fight against antibiotic resistant strains.

Thiiobenzyhdrazide (Htbh) and its Cu(II) complexes, [Cu(Htbh)2Cl2] and [Cu(tbh)2] were synthesized and characterized by various physicochemical studies. In vivo and in vitro antitumour activity of Htbh, [Cu(Htbh)2Cl2] and [Cu(tbh)2] has been tested. LD50 values were calculated for all the three compounds. It was observed that the antitumour effect of [Cu(Htbh)2Cl2] is maximum. Light microscopic study of the treated tumour mass demonstrated that certain cellular degradation, such as disappearance of mitotic figures, loss in cellular compactness, distortion of nucleus and disruption of cytoplasmic boundaries, takes place in the tumour region of complex treated mice. Further, tumour bearing mice administered with Cu(II) complexes showed reversal of tumour growth associated induction of apoptosis in lymphocytes.

The qualitative and quantitative analysis of an antibiotic drug, 5-amino-1 cyclopropyl-7 (cis-3, 5 dimethyl-1-piperazyl)-6,8- dihydro-1, 4 dihydro-4-oxo-3-quinoline carboxylic acid (Sparfloxacin, SFX) and its pharmaceutical formulation i.e.sparx-100 tablet, has been done using polarographic and amperometric methods. Complexation behavior of SFX with Fe(II), both in solid and liquid phases has been studied by elemental analysis, IR.-spectra and polarographic and amperometric methods. SFX produces a single cathodic reduction wave in 0.1 M ammonium tartrate (supporting electrolyte) at pH 6.0 +/-0.1. The wave is diffusion controlled and wave height is proportional to the concentration of SFX. The complex is also reversibly reduced at the electrode surface with diffusion-controlled kinetics. The stoichiometry of the Fe(II)- SFX complex is 1:1. Antibacterial studies on the drug and its metal complex have been performed against different bacteria. The observed results revealed the complex to be more potent in its antibacterial activity as compared to the parent drug. On the basis of observed results it could be concluded that the prepared Fe(II)- SFX complex may be recommended to the therapeutic experts for its possible use as a more potent antibiotic drug.

A series of diorganotin dicarboxylates of the general formula (CH(3))(2)Sn(OCOCHR(3)CHR(2)GeR(1))(2) where R(1)=(C(6)H(5))(3), (P-CH(3)C(6)H(4))3, N(CH(2)CH(2)O)(3), R(2)=C(6)H(5), H, CH(3), P-CH(3)OC(6)H(4), P-ClC(6)H(4), P-CH(3)C(6)H(4), R(3)=CH(3) and H, have been synthesized by the reaction of dimethyltin oxide with germanium substituted propionic acid in 1:2 molar ratio in toluene. The H(2)O formed was removed azeotropically using a Dean and Stark apparatus. All the compounds have been characterized by IR, multinuclear ((1)H, (13)C, (119)Sn) NMR, mass and Mössbauer spectroscopies. All compounds were found to have potential activity against bacteria.

The results of cytotoxicity trials against a panel of seven human cell lines for a series of triorganophosphinegold(I) 3- and 4-mercaptobenzoates are reported. While the new compounds show moderate to high toxicity, their potencies are inferior to those reported previously for their isomeric 2- mercaptobenzoate derivatives. The results therefore suggest a structure-activity relationship in that the 2-isomeric species are more active, particularly against the non-small cell lung cancer and renal cancer cell lines, results that may indicate some selectivity in their cytotoxic profile.

Superoxide dismutase (SOD) is the scavenger of superoxide anion (O2(-)) and functions as a protector of living bodies. Study of a model compound of SOD is important when searching for the relationship between functions and structures of enzymes. Furthermore, SOD model compounds have potential for therapeutic usefulness. Although many SOD: model compounds have been reported, their structures are quite different from those of the native enzyme. Cu,Zn-SOD has been proposed for clinical uses. Unfortunately, many problems such as half-lifetime and antigenicity have not been overcome even though several copper(II) complexes are known to show SOD activity. Active oxygen species such as superoxide (O2(-)) from various components of the cellular electron transport chains, and provided during the respiratory burst of phagocytic cells, have been implicated both in the aging process and in degenerative diseases, including arthritis and cancer. Therefore, the biological system posseses the protective mechanisms against active species.

O-Cholesteryl-O-phenyl-N-phenylphosphoramidate (1) and four organotin (lV) derivatives of the ambidentate O-cholesteryl-O -phenyl phosphorothioate ligand formulated as Me(3) SnOSPR'R"(2), Ph(3)SnOSPR'R"(3), O(CH(2)CH(2)S)(2)Sn(n-Bu)OSPR'R"(4), S(CH(2)CH(2)S)(2)Sn(n-Bu)OSPR'R"(5), (R' = O-phenyl; R"= O-cholesteryl) were subjected to cytotoxicity screening against KB (nasopharingel carcinoma), OVCAR-5 (ovarium carcinoma) and SQC-1 UlSO (squamous cell cervix carcinoma) cell cultures. The results of the bioassay showed that these compounds possess potent antitumor activities against the studied human carcinoma cell lines.

Some antifertility inhibitors of 18 to 24-membered tetraazamacrocyclic complexes of iron(II) and manganese(II) have been synthesised by the template condensation using 1,3-phenylenediamine with malonic acid, succinic acid, glutaric acid and adipic acid. The reaction proceed smoothly to completion. The complexes were characterized by elemental analyses, molecular weight determinations, infrared, electronic, magnetic moment, mössbaur and mass spectral studies. The elemental analyses are consistent with the formation of the complexes [M(N(4)L(n))Cl(2)] (M = Fe(lI) or Mn(II)). All these complexes are stable and monomeric in nature as indicated by the molecular weight determinations. The spectral studies confirm the octahedral geometry around the central metal atom. The complexes have been screened in vitro against a number of fungi and bacteria to assess their growth inhibiting potential. The testicular sperm density and testicular sperm morphology, sperm motility, density of cauda epididymal spermatozoa and fertility in mating trials and biochemical parameters of reproductive organs have been examined and discussed.