Metal-Based Drugs最新文献

Some ruthenium(III) complexes with aryl-azo 2,4-pentanedione as co-ligands (L(1)H - L(3)H(2)) have been synthesized and characterized spectroscopically IR, (1)H NMR, UV/Vis, ESR, conductimetric) along with elemental analysis and FAB-mass data. Their luminescent and redox properties have been studied. The antibacterial, anti-HIV and antitmnour activities have also been reported.

A square planar copper complex of derivatized NSAID drug (Ketoprofen thiosemicarbazone [3-benzoyl-alpha-methyl benzene acetic acid thiosemicarbazone]), is characterized by elemental analysis, spectroscopy, electrochemistry and magnetic susceptibility studies which exhibits dose-dependent and enhanced antiproliferative effects on human breast cancer cell line T47D rich in progesterone receptors.

The preparation and characterization of two triorganophosphinegold(I) complexes containing the anion derived from thiobenzoic acid are described. The cytotoxicity of these complexes has been investigated along with that of triphenylphosphinegold(I) mercaptopurinate, a known anti-tumor compound, against a variety of human cell lines. The complexes showed moderate to high cytotoxicity (ID(50) 250 - 2500 ng/ml).

Six new N-substituted di- and tributyltin 2-aminoethanethiolates (cysteaminates) have been prepared and characterised by (1)H, (13)C and (119)Sn NMR spectroscopy. All these compounds exhibit a good in vitro antifungal effect against selected types of human pathogenic fungi (Candida albicans, Candida krusei, Candida tropicalis, Candida glabrata, Trichosporon beigelii, Aspergillus fumigatus, Absidia corymbifera, Trichophyton mentagrophytes) and their activity is comparable with that of some antifungal drugs commonly used in the clinical use like ketoconazole. The structure-activity relationships in these compounds are discussed.

The synthesis and characterization of two Pt(II) Complexes with the isomeric ligands 4,5-dihydro-5-oxo- [1,2,4]triazolo-[ 1,5-a]pyrimidine (5HtpO) and 4,7-dihydro-7-oxo-[ 1,2,4]-triazolo-[ 1,5-a]pyrimidine (7HtpO) are described, as well as a Ru(III) complex with 7HtpO. The crystal structure of cis-[PtCl(2)(7HtpO)(2)].2H(2)O has been solved by X-ray diffraction analysis. In vitro activity of the new isolated complexes against the epimastigote form of T. cruzi, procyclic form of T. b. brucei and promastigote form of L. donnovani and P. characias has also been studied. The three complexes markedly affect the growth of the parasites and none of them shows cytotoxicity against macrophage of the J774.2 line at the heaviest dosages used.

Erbium(III) complexes of 2-hydroxy-l,4-naphthalenedione-1-oxime and its C-3 substituted derivatives are synthesized and characterized by elemental analysis, thermogravimetric analysis, infrared spectroscopy, magnetic susceptibility measurements 2-hydroxy-1,4-naphthalenedione-1-oxime derivatives are analysed using (1)H and (13)C NMR spectroscopy. The molecular composition of the synthesized complexes is found to be [ML(3)(H(2)O)(2)]. The antimicrobial activity of these complexes is determined by well diffusion method against the target microorganisms- Staphylococcus aureus, Xanthomonas campestris, Pseudomonas aeruginosa, Candida albicans and Aspergillus niger. The antimicrobial activities of 2- hydroxy-1,4-naphthalenedione-1-oximes and their complexes are compared. It is observed that 2-hydroxy-1,4-naphthalenedione-l-oximes exhibit higher antifungal activity as compared to antibacterial activity. These activities are reduced upon complexation of these oximes with Erbium.

Triphenyltin coumarin-3-carboxylate and its coordination complexes with ethanol, triphenylphosphine oxide, triphenylarsine oxide, diphenylcyclopropenone and quinoline N-oxide exhibited high in vitro cytotoxicity (LC(50) values in the range 0.25-3.4 mug/mL) when tested against EBV-DNA positive Raji cells and P-388 leukaemia cells, compared to the standard drug 5-Fluorouracil, which showed LC(50) values of 11 and >50 mug/mL, respectively, against these cells. Additional tests performed on the Raji cells incubated with the quinoline N-oxide complex in the presence of the tumour promoters, TPA and sodium butyrate, revealed that the diffused and restricted protein components of the early antigen complex were suppressed relative to the control containing only the promoters, indicating impaired function of the genes involved as transactivators in the early lytic cycle of the EBV. The failure of the restriction enzymes Eco R1 and Hind III to cleave the extracted DNA from such treated cells in contrast to the control, coupled with the amplification of the BMLF-1 gene by the PCR technique which was realised only with the DNA of the control and not of the treated sample, point to a punitive interaction of the organotin with the nuclear DNA of the Raji cells.

The interaction of binuclear rhodium(II) complexes [Rh(2)(OOCCH(3))(4)(H(2)O)(2)], [Rh(2){OOCCH(OH)Ph}(2)(phen)(2)(H(2)O)(2)] {OOCCH(OH)Ph}(2), [Rh(2)(OOCCH(3))(2)(bpy)(2)(H(2)O)(2)](OOCCH(3))(2) and [Rh(2)Cl(2)(OOCMe)(2)(bpy)(2)](3H(2)O) with ceruloplasmin, cysteine, glutathione and coenzyme A have been investigated using. UV-Vis and CD spectroscopies. The complexes containing phen or bpy at pH = 7.4 and 4.0 are readily reduced with sulfhydryl compounds, while rhodium(II) acetate is relatively stable in these conditions. Complex [Rh(2){OOCCH(OH)Ph}(2)(phen)(2)(H(2)O)(2)] strongly changes structure of ceruloplasmin leading to the decrease of of alpha-helix content and loss of oxidase activity.

Zinc, magnesium, aluminum and copper complexes of several potent, clinically used carbonic anhydrase (CA) sulfonamide inhibitors, such as acetazolamide, methazolamide, ethoxzolamide and benzolamide were tested for their possible applications as antacids, in experimental animals. Gastric acid secretion parameters 3 days after treatment with these CA inhibitors (2 x 500 mg, twice a day), in dogs with chronic gastric fistulas, led to the observation that the gastric acid parameters BAO (the basal acid output), and MAO (the maximal acid output after stimulation with histamine) were drastically reduced, as compared to the same parameters in animals that did not receive these enzyme inhibitors. These are promising results for the possible use of metal complexes of heterocyclic sulfonamides as treatment alternatives (alone or in combination with other drugs) for gastric acid secretion imbalances.

Delivery agents which can carry the {Ru(NO)}(6) chromophore ("caged NO") are desired for vasodilation and for photodynamic therapy of tumors. Toward these goals, complexes derived from [RuCl(3)(NO)(H(2)O)(2)]= (1) have been prepared using dipyridylamine (dpaH) as mono and bis adducts, [Ru(NO)Cl(3)(dpaH)] = (2) and [Ru(NO)Cl(dpaH)(2)]Cl(2) = (3). The dpaH ligands coordinate cis to the Ru(NO) axis.The mono derivative is a model for a potential DNA groove-spanning binuclear complex {[RuNO)Cl(3)](2)(tpada)} = (4) which has two DNA-coordinating Ru(II) centers, photo-labile {Ru(NO)}(6) sites, and a groove-spanning tether moiety.The binuclear assembly is prepared from the tethered dipyridylamine ligand N,N,N',N'-tetrakis(2-pyridylmethyl)adipamide (tpada) which has recently been shown to provide a binuclear carrier complex suited to transporting Ru(II) and Pd(II) agents. A related complex, [Ru(NO)Cl(pida)] = (5) with the {Ru(NO)}(6) moiety bound to (2-pyridylmethyl) iminodiacetate (pida(2-)) is also characterized as a potential "caged NO" carrier. Structural information concerning the placement of the pyridyl donor groups relative to the {Ru(NO)}(6) unit has been obtained from (1)H and (13)C NMR and infrared methods, noting that a pyridyl donor trans to NO+ causes "trans strengthening" of this ligand for [Ru(NO)Cl(pida)], whereas placement of pyridyl groups cis to NO+ causes a weakening of the N-O bond and a lower NO stretching frequency in the dpa-based complexes.