Metal-Based Drugs最新文献

Bacterial screening employing the agar diffusion test on triphenyltin carboxylates containing various functional residues in the ester moiety revealed appreciable differences in their activities relative to triphenyltin acetate. Among these, [3-(Diethylphosphono)propionato] triphenyltin (1) and [N-cyclohexylcarbamoyl) glycinato] triphenyltin displayed activities comparable to tri-n-butyltin cinnamate (2) towards both Gram-positive and Gram-negative bacteria; the latter compound was the most active among the eleven triorganotin compounds tested, which included cyclopentyldiphenyltin hydroxide (3) and its methacrylate derivative. Applying the more quantitative plate count and optical density tests on compounds 1-3, it was shown that their inhibitory activity ranked in the order 2 > 3 >1. Significantly, 3 caused around 90% inhibition of both Eschechia coli (-) and Pseudomonas aeruginosa (-) when incubated for 24 h at 37+/-1 at the 10.0 mug/ mL concentration level. Compound 2 was less effective against P.aeruginosa than against E.coli. While the Gram-positive bacteria were all readily inhibited, Bacillus subtilis (+) appeared to the most susceptible among them towards the test compounds.

Six new compounds [(CpTi)X, Cp=upsilon(nabla)-c(nabla)H(nabla), X=Ge, Ga, B) have been prepared and their Keggin structures determined by elementary analysis, IR, UV, (infinity)H NMR and (infinity for all)WNMR spectrometry. The results show that the complexes retain Keggin structure. The complexes exhibit antitumoral activity in vitro as shown by MTT experiment.

Complexes of 2-(4-thiazolyi)benzimidazole (thiabendazole, THBD) with Co(II), Ni(II), Cu(ll) of general formula ML(2)(NO(3))(2) H(2)O and complexes of Pd(II) and Pt(II) of general formula ML2Cl(2) H(2)O have been obtained and characterized by elemental analyses, IR and far IR spectroscopy and magnetic measurements. The X-ray crystal structure of the copper(II) complex has been determined. The in vitro cell proliferation inhibitory activity of these compounds was examined against human cancer cell lines A 549 (lung carcinoma), HCV-29 T (urinary bladder carcinoma), MCF-7 (breast cancer), T47D (breast cancer), MES-SA (uterine carcinoma) and HL-60 (promyelocytic leukemia). Pt-THBD has been found to exhibit an antileukemic activity of the HL-60 line cells matching that of an arbitrary criterion.

The cytotoxicity of four Co(III) complexes of arginine on nontumour MDBK cells and on two cell lines derived from transplantable tumors, LSCC-SF(Mc29) and LSR-SF (SR), was evaluated comparative!y. Based on the cytotoxic concentration required to inhibit cell surveillance by 50% cc(nabla') it was found that: (i) the cytotoxicity of complexes tested increases when the concentration decreased; (ii) the cell surveillance depends on both complex and cell specificities. The complex specificity was illustrated by the order 1 > 4 > 2 >/= 3 . The cell specific response was demonstrated by the fact that LSCC-SG (Mc29) cells were up to 60 times more sensitive to 1 while LSR-SF (SR) cells were up to 1000 times more sensitive to 2 as compared to MDBK cells. Furthermore, with the prolongation of action on nontumour cells the cytotoxicity of 4 decreased up to 300 times while for both tumour cells it was independent on the duration of action.

Trans-[PtCl(2)(N,N-dimethylamine)(isopropylamine)] is a novel trans-platinum compound that shows cytotoxic activity in several cisplatin resistant cell lines. The aim of this paper was to analyse, by means of molecular cell biology techniques and total reflection X-ray fluorescence (TXRF), the cytotoxic activity, the induction of apoptosis, the cellular uptake and the DNA binding of trans-[PtCl(2)(N,N-dimethylamine)(isopropylamine)] in the cisplatin resistant cell line A2780cisR. The results show that this drug is more cytotoxic and induces a higher amount of apoptotic cells than cisplatin in A2780cisR cells. However, the intracellular accumulation and extent of binding to DNA of trans-[PtCl(2)(N,N-dimethylamine)( isopropylamine)] is lower than that of cis-DDP. Moreover, trans-[PtCl(2)(N,N-dimethylamine)(isopropylaminae)] is partially inactivated by intracellular levels of glulathione. The result suggest that circumvention of ciplatin resistance by trans-[PtCl(2)(N,N-dimethylamine)(isopropylamine)] in A2780cisR cells might be related with the ability of this drug to induce apoptosis.

Acylhydrazine derived furanyl and thienyl Schiff bases and their Cu(II) complexes have been prepared and characterized on the basis of their physical, spectral and analytical data. The preferred enolic form of the Schiff base function as a tetradentate ligand during coordination to the metal ion yielding a square planar complex. The Schiff bases and their complexes with different anions were tested for their antibacterial activity against bacterial species such as Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa andKlebsiella pneumonae.

We synthesized a novel anticancer agents based on mixed chelate copper (II) complexes, named Casiopeínas((R)) has of general formula [Cu(N-N)(N-O)H(2)O]NO(3) (where, N-N = diimines as 1,10- phenanthroline, 2,2-bipyridine, or substituted and N-O=aminoeidate or [Cu(N-N)(O-O)H(2)O]NO(3) (where NN= diimines as 10-phenanthroline, 2,2-bipyridine or substituted Casiopeínas I, II, IV, V, VI, VII VIII and O-O=acetylacetonate, salicylaldehidate Casiopínas III). We evaluated the in vitro antitumor activity using a human cancer cell panel and some nurine cancer cells. Eleven Casiopeinas are evaluated in order to acquire some structure-activity correlations and some monodentated Casiopeinäs analogues; cisplatinum was used as control drug. The 50% growth inhibition observed is, in all cases reach with concentrations of Casiopeina's 10 or 100 times lower than cisplatinum. In a previous work we reported the induction of apoptosis by Casiopeina II. The results indicate that Casiopeinass are a promising new anticancer drug candidates to be developed further toward clinical trials.

With the aim to improve and extend the antiviral activity of the antiherpic drug penciclovir, to a wider spectrum of viruses, we have synthesized and characterized new binary and ternary complexes of Pd(II) of formulae cis-(pen)(2)PdCl(2) and cis,[(nucl)(2)Pd(pen)(2)]Cl(2), where nucl = guanosine, inosine, cytidine or penciclovir. The characterization was mainly based on IR and (1)H NMR spectroscopy, and the results showed that in all prepared complexes, penciclovir coordinates to the metal through N7. The far-i.r. spectrum of the complex cis-(pen)(2)PdCl(2) confirmed the cis- geometry around Pd(II). All the prepared complexes were markedly active against HSV-1 and HSV-2 strains, but not against thymidine kinase-deficient HSV-1 strains.

Silicon and germanium containing heteroaromatic sulfides have been prepared using phase transfer catalytic (PTC) system thiol / Si or Ge containing alkyl halide / solid KOH / 18- crown-6 / toluene. The target sulfides were isolated in yields up to 92 %. It has been found that 2-{[dimethyl (beta-triethylgermylethyl)-silylmethyl]thio}-1-methylimidazole and 2-{[dimethyl(beta-triphenylsilylethyl) silyl-methyl]thio}benzothiazole are the most active cholesterol level lowering and vasodilating agents.

Antioxidant properties of three Curcumin derivatives in which the 1,3-diketone system is appended with nitrogen and sulfur donors and their copper conjugates are examined for the first time. Metal conjugation seems to offer distinct advantages in radical scavenging activities of curcumin compounds.