Metal-Based Drugs最新文献

A series of silyl, germyl and alkyl substituted trifluoroacetylfurans has been synthesized under Friedel-Crafts electrophilic acylation conditions. Biological investigations have demonstrated that germyl derivatives of trifluoroacetylfuran are more toxic than the silicon analogues. 5-Triethylgermyl-2- trifluoroacetylfuran was the most toxic compound (CD(nabla), 11.2 mg kg(-1), i.p. for white mice), 200 times more toxic than the silicon analogue. 5-t-Butyl- and 5-trimethylsilyl-2-trifluroacetylfuran prolong the duration of ethanol anaesthesia by 220 and 140%. 5-Triethylgermyl-2-trifluroacetylfuran exibited high anesthetic activity in hexobarbital test (prolonged the duration by 137%). Some of compounds influenced muscle tone and locomotor coordination parameters. 5-Triethylgermyl-2-trifluomacetylfuran exibited analgesic activity (D(nabla), 0.9 mg k}(-infinity)).

Antithrombotic effect of the copper-aspirin complex (dimeric copper(II) bis(o-acetoxybenzoate) was evaluated in the model of venous thrombosis; its effects on platelet-neutrophil adhesion were investigated by use of rosette assay. The results showed that the intragastrically administered copper-aspirin complex (5, 7, and 10 mg kg(-1)) dose-dependently lowered the wet and dry thrombus weight; it significantly decreased the binding of arachidonic acid-activated platelets to neutrophils with an IC(50) value of 41.5 mumol L(-1). The results suggested that copper aspirinate inhibited platelet-neutrophil adhesion and resulted in a more potent antithrombotic activity.

Schiff bases were obtained by condensation of 2-amino-l,3,4-thiadiazole with 5-substituted-salicylaldehydes which were further used to obtain complexes of the type [M(L)(2)]Cl(2), where M=Co(II), Cu(II), Ni(II) or Zn(II). The new compounds described here have been characterized by physical, spectral and analytical data, and have been screened for antibacterial activity against several bacterial strains such as Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa. The antibacterial potency of these Schiff bases increased upon chelation/complexation, against the tested bacterial species, opening new aproaches in the fight against antibiotic resistant strains.

In order to better define the mechanism and the products of guanine oxidation within DNA, we investigated the details of the mechanism of guanine oxidation by a metalloporphyrin, Mn-TMPyP, associated to KHSO(5) on oligonucleotides. We found that the three major products of guanine oxidation are formed by independent reaction routes. The oxidized guanidinohydantoin (1) and the proposed spiro compound 3 derivatives are not precursors of imidazolone lesion (Iz). These guanine lesions as well as their degradation products, may account for non-detected guanine oxidation products on oxidatively damaged DNA.

NAMI-A, imidazolium trans-imidazoledimethylsulfoxidetetrachlororuthenate, is a ruthenium based compounds capable of inhibiting the growth of lung metastases of solid tumours in a number of experimental conditions.The aim of this study was to investigate the potential use of NAMI-A by the oral route to treat lung metastases of MCa mammary carcinoma in the CBA mouse. treatment of mice, carrying intramuscular tumours in advanced stage of growth, for 11 consecutive days caused a significant reduction of the weight of lung metastases over the range of doses from 150 to 600 mg/kg/day. No sign of toxicity was observed at the histological analysis in the gut epithelium or in the kidney parenchyma, and NAMI-A concentration in the kidney was more than 10-fold lower than after intraperitoneal treatments. NAMI-A is thus active against metastases also by the oral route, suggesting the use of this way to treat tumour bearing hosts for long periods.

Some novel transition metal [Co(II), Cu(II), Ni(II) and Zn(II)] complexes of substituted pyridine Schiff-bases have been prepared and characterized by physical, spectral and analytical data. The synthesized Schiff-bases act as deprotonated tridentate for the complexation reaction with Co(II), Ni(II) and Zn(II) ions. The new compounds, possessing the general formula [M(L)(2)] where [M=Co(II), Cu(II), Ni(II) and Zn(II) and HL=HL(1), HL(2), HL(3) and HL(4)] show an octahedral geometry. In order to evaluate the effect of metal ions upon chelation, the Schiff bases and their complexes have been screened for antibacterial activity against the strains such as Escherichia coli,Staphylococcus aureus, and Pseudomonas aeruginosa. The complexed Schiff bases have shown to be more antibacterial against one more bacterial species as compared to uncomplexed Schiff-bases.

In this paper we report the stepwise preparation and the characterization of new unsymmetrical monoanionic Ru(III) dinuclear compounds, [NH(4)][{trans-RuCl(4)(Me(2)SO-S)}(mu-L){mer-RuCl(3)(Me(2)SO-S)(Me(2)SO-O)}] (L = pyz (1), pym (2)). By a similar synthetic approach we also prepared new mixed-valence Ru(III)/Ru(II) dinuclear compounds of formula [NH(4)][{trans-RuCl(4)(Me(2)SO-S)}(mu-pyz){cis,cis,cis-RuCl(2)(Me(2)SO-S)(2)(CO)}] (L = pyrazine (pyz, 3), pyrimidine (pym, 4)). Moreover, we describe the chemical behavior of compounds 1-4 in physiological solution, also after complete reduction (with ascorbic acid) to the corresponding Ru(II)/Ru(II) species. Overall, the chemical behavior of 1 and 2 after reduction resembles that of the corresponding dianionic and neutral dinuclear species, [{trans-RuCl(3)(Me(2)SO-S)}(2)(mu-L)](2-)and [{mer-RuCl(3)(Me(2)SO-S)(Me(2)SO-O)}(2) (mu-L)]. On the other hand, the mixed-valence dinuclear compounds 3 and 4, owing to the great inertness of the cis,cis,cis-RuCl(2)(Me(2)SO-S)(2)(CO)(1/2mu-L) fragment, behave substantially like the mononuclear species [trans-RuCl(4)(Me(2)SO-S)(L)](-) in which the terminally bonded L ligand can be considered as bearing a bulky substituent on the other N atom.

When an oligonucleotide containing a 1,3-(G,G)-transplatin cross-link at a GNG site (N represents a C, T, A or U residue) is paired with its complementary strand, the intrastrand adduct rearranges into an interstrand cross-link, resulting in the covalent attachment of both strands. Here, we have studied the influence of the inert ligands of the platinum(II) complex and of the nucleotide residues in the vicinity of the adduct on the rearrangement reaction. Dramatic effects on the linkage isomerization rate could be 37. The results are analyzed in relation with the mechanism of rearrangement of the 1,3-intrastrand adducts into interstrand cross-links. The relevance of platinated oligonucleotides as potent and specific drugs is discussed.

Treatment with essential metalloelement (Cu, Fe, Mn, and Zn) chelates or combinations of them before and/or after radiation injury is a useful approach to overcoming radiation injury. No other agents are known to increase survival when they are used to treat after irradiation, in a radiorecovery treatment paradigm. These chelates may be useful in facilitating de novo syntheses of essential metalloelement-dependent enzymes required to repair radiation injury. Reports of radioprotection, which involves treatment before irradiation, with calcium-channel blockers, acyl Melatonin homologs, and substituted anilines, which may serve as chelating agents after biochemical modification in vivo, as well as Curcumin, which is a chelating agent, have been included in this review. These inclusions are intended to suggest additional approaches to combination treatments that may be useful in facilitating radiation recovery. These approaches to radioprotection and radiorecovery offer promise in facilitating recovery from radiation-induced injury experienced by patients undergoing radiotherapy for neoplastic disease and by individuals who experience environmental, occupational, or accidental exposure to ultraviolet, x-ray, or gamma-ray radiation. Since there are no existing treatments of radiation-injury intended to facilitate tissue repair, studies of essential metalloelement chelates and combinations of them, as well as combinations of them with existing organic radioprotectants, seem worthwhile.

Some ruthenium (II) polypyridyl complexes with a bis-chalcone (obtained by the condensation of 3-methyl-thiophene-2-carboxaldehyde and 4-acetyl pyridine) have been synthesized and characterized spectroscopically (IR, NMR, UV/Vis), conductimetric, elemental analysis and FAB mass data. Their luminescent, redox and Li(+) binding properties have been studied. The anti-HIV and antitumour activities have also been reported.