Metal-Based Drugs最新文献

Co(II) and Ni(II) complexes with a Schiff base, N-(2-furanylmethylene)-2-aminothiadiazole have been prepared and characterized by their physical, spectral and analytical data. The synthesized Schiff-bases act as tridentate ligands during the complexation reaction with Co(II) and Ni(II. metal ions. They possess the composition [M(L)(2)]X(n) (where M=Co(II) or Ni(II), L=, X=NO(3) (-), SO(4) (2-), C(2)O(4) (2-) or CH(3)CO(2) (-) and n=1 or 2) and show an octahedral geometry. In order to evaluate the effect of anions upon chelation, the Schiff-base and its complexes have been screened for antibacterial activity against bacterial strains e.g., Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa.

N6-Benzoyladenine-cyanoborane (2), and 6-triphenylphosphonylpurine-cyanoborane (3) were selected for investigation of cytotoxicity in murine and human tumor cell lines, effects on human HL-60 leukemic metabolism and DNA strand scission to determine the feasibility of these compounds as clinical antineoplastic agents. Compounds 2 and 3 both showed effective cytotoxicity based on ED(50) values less than 4 mug/ml for L1210, P388, HL-60, Tmolt(3), HUT-78, HeLa-S(3) uterine, ileum HCT-8, and liver Hepe-2. Compound 2 had activity against ovary 1-A9, while compound 3 was only active against prostate PL and glioma UM. Neither compound was active against the growth of lung 549, breast MCF-7, osteosarcoma HSO, melanoma SK2, KB nasopharynx, and THP-1 acute monocytic leukemia. In mode of action studies in human leukemia HL-60 cells, both compounds demonstrated inhibition of DNA and protein syntheses after 60 min at 100 muM. These compounds inhibited RNA synthesis to a lesser extent. The utilization of the DNA template was suppressed by the compounds as determined by inhibition of the activities of DNA polymerase alpha, m-RNA polymerase, r-RNA polymerase and t-RNA polymerase, which would cause adequate inhibition of the synthesis of both DNA and RNA. Both compounds markedly inhibited dihydrofolate reductase activity, especially in compound 2. The compounds appeared to have caused cross-linking of the DNA strands after 24 hr at 100 muM in HL-60 cells, which was consistent with the observed increased in ct-DNA viscosity after 24 hr at 100 muM. The compounds had no inhibitory effects on DNA topoisomerase I and II activities or DNA-protein linked breaks. Neither compound interacted with the DNA molecule itself through alkylation of the nucleotide bases nor caused DNA interculation between base pairs. Overall, these antineoplastic agents caused reduction of DNA and protein replication, which would lead to killing of cancer cells.

Five coordinated novel complexes of CuII and NiII have been synthesized from benzil and 1,3- diaminopropane-CuII/NiII complex and characterized by elemental analysis, i.r., n.m.r., e.p.r, molar conductance and u.v-vis, spectroscopy. The complexes are ionic in nature and exhibit pentaeoordinated geometry around the metal ion. The reaction kinetics of C25H36N5O2CuCl with calf thymus DNA was studied by u.v-vis, spectroscopy in aqueous medium. The complex after interaction with calf thymus DNA shows shift in the absorption spectrum and hypochromicity indicating an intercalative binding mode. The Kobs values have been calculated under pseudo-first order conditions. The redox behaviour of complex C25H36N5O2CuCl in the presence and in the absence of calf thymus DNA in the aqueous solution has been investigated by cyclic voltammetry. The cyclic voitammogram exhibits one quasi-reversible redox wave corresponding to CuII/CuI redox couple with E1/2 values of -0.377 and -0.237 V respectively at a scan rate of 0.1Vs-1 .On interaction with calf thymus DNA, the complex C25H36N5O2CuCl exhibits shifts in both Ep as well as in E1/2 values, indicating strong binding of the complex to the calf thymus DNA.

Apoptosis induced by rhodium II amidate, rhodium II propionate, cisplatin and interactions with dexamethaxone were studied on some human leukemia cell lines Raji, Jurkat and U937. Apoptosis was studied by flow cytometry, agarose gel electrophoresis and morphological analysis. Rhodium II propionate induced apoptosis in all the three cell lines, Rhodium II amidate, in the lymphoid cell lines Jurkat and Raji, and cisplatin, only in the Jurkat, a T lymphoid cell line. It has also been observed that the addition of dexamethasone enhances the apoptosis index only in U937, a monocytic line with a glucocorticoid receptor bearing.

A series of new barbituryl/thiobarbituryl substituted organomercurial derivatives 3a-i have been synthesised from pyrimidine derivatives 1a-c and arylmercuric chloride 2a-c over K(2)CO(3) under microwave irradiations (MWI). This solventless synthesis apart from eliminating organic solvent from workup step, also gave improved yield as compared to the conventional heating, with reaction time reduced from hours to minutes. The prepared compounds were tested against A. niger and A. flavous for their antifungal activity and were found to posses good activity.

A number of organosilicon and organogermanium derivatives and some related compounds including the N-substituted. 2-[1-naphthylmethyl]-2-imidazoline and 2-[1-(1-naphthyl)ethyl]-2-imidazoline have been prepared and the toxicity of some compounds have been determined in mice. In this paper we report the synthesis and the evaluation of the pharmacological activity of new organosilicon and organogermanium, compounds such as sila- and germadithioacetals derived from N-substituted naphthylimidazolne.

The complexes [Ru([9]aneS(3))(dppz)Cl]Cl 1 and [Ru([12]aneS(4))(dppz)]Cl(2)2 ([9]aneS(3) = 1,4,7- trithiaciclononane and [12]aneS(4) = 1,4,7,10-tetrathiaciclododecane) were synthesised and fully characterised. These complexes belong to a small family of dipyridophenazine complexes with non-polypyridyl ancillary ligands . Interaction studies of these complexes with CT-DNA (UV/Vis titrations, steady-state emission and thermal denaturation) revealed their high affinity for DNA . Intercalation constants determined by UV/Vis titrations are of the same order of magnitude (10(6)) as other dppz metallointercalators, namely [Ru(II)(bpy)(2)dppz]S(2+). Differences between l and2 were identified by steady-state emission and thermal denaturation studies . Emission results are in accordance with structural data, which indicate how geometric distortions and different donor and/or acceptor ligand abilities affect luminescence. The possibility of noncovalent interactions between ancillary ligands and nucleobases by van der Waals contacts and H-bridges is discussed . Furthermore, complex l undergoes aquation under intra-cellular conditions and an equilibrium with the aquated form l' is attained . This behaviour may increase the diversity of available interaction modes.

Tetraethyldicyanoborane pyrophosphate (2) and 3'-(diethylphosphite-cyanoborano)-5'-dimethoxytrityl.N(4)-benzoyl-deoxycytidine (3) have been synthesized in 70% and 76% yields, respectively. The compatibility of the substituted boranophosphates with common protecting groups is hereby demonstrated.Boron containing biologically active compounds, such as nucleosides and nucleotides (1-6) and amino acids (7-9) are important due to their potential therapeutic activity, research and diagnostic applications. Many boron containing compounds have shown promising activity as anticancer, (10.) (11.) (12) antiinflammatory,(13) and antiosteoporotic (13)agents. Oligonucleotdes in which a non-bridging oxygen atom is replaced by a borane(BH(3)) group are a very important class of modified nucleic acids. (1.) (3.) (14-16) The BH(3) group is isoelectronic with oxygen in natural oligonucleotides and isoelectronic and isostructural with the oligonucleotide methyl phosphonates, which are nuclease resistant. On the other hand, the alpha-borano triphosphates are good substrates for DNA polymerases and incorporation of boranophosphates into DNA causes an increase in the resistance to exo- and endonucleases (2.) (17a) as compared to non-modified DNA. There are also notable applications of the alpha-borano triphosphates in PCR sequencing (17a) and nucleic acid detection (17b).

Synthesis, characterization and antimicrobial activities of an interesting class of biologically potent macrocyclic complexes have been carried out. All the complexes have been evaluated for their antimicrobial effects on different species of pathogenic fungi and bacteria. The testicular sperm density, testicular sperm morphology, sperm motility, density of cauda epididymal spermatozoa and fertility in mating trails and biochemical parameters of reproductive organs have been examined and discussed. The resulting biologically active [M(MaL(n))(R(2))]Cl(2) and [Pb(MaL(n))(R(2))X(2)] (where, M = Pd(II) or Pt(II) and X = Cl or NO(3)) type of complexes have been synthesized by the reactions of macrocyclic ligands (MaL(n)) with metal salts and different diamines in 1:1:1 molar ratio in methanol. Initially the complexes were characterized by elemental analyses, molecular weight determinations and conductivity measurements. The mode of bonding was established on the basis of IR, (1)H NMR, (13)C NMR, (195)Pt NMR, (207)Pb NMR, XRD and electronic spectral studies. The macrocyclic ligand coordinates through the four azomethine nitrogen atoms which are bridged by benzil moieties. IR spectra suggest that the pyridine nitrogen is not coordinating. The palladium and platinum complexes exhibit tetracoordinated square-planar geometry, whereas a hexacoordinated octahedral geometry is suggested for lead complexes.