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At least 595 records · Page 33Linked to original sources
PubMed2003

C-c bond formation through oxidatively induced elimination of platinum complexes--a novel approach towards conjugated macrocycles.

A novel and effective method for the synthesis of conjugated macrocycles is described. By the self-assembly of conveniently accessible building blocks to a metalla-macrocycle, and subsequent C-C bond formation through elimination of transition metal units, the strained cyclodimeric terthiophene-diyne 4 -as a precursor for cyclo[8]thiophene 5- was synthesized in a good overall yield.

Journal Article↗
PubMed2003

[Chiral separation of drugs based on macrocyclic antibiotics using HPLC, supercritical fluid chromatography (SFC) and capillary electrochromatography (CEC)].

Separation of enantiomers by means of high-performance liquid chromatography (HPLC), supercritical fluid chromatography (SFC), and capillary electrochromatography (CEC) is of great importance in pharmaceutical analyses. In recent years, separation of various types of racemates employs most frequently chiral stationary phases based on macrocyclic antibiotics. This class of chiral selectors includes vancomycin, teikoplanin, ristocetin A, teikoplanin without saccharide components, avoparcin, etc. The review paper describes the properties of selected antibiotics, the effect of chromatographic conditions on enantioselectivity (effect of the composition of the mobile phase, effect of pH of the mobile phase, effect of temperature), and the study of possible mechanisms of interaction, which play an important role in the separation of enantiomers. Examples of the use of macrocyclic antibiotics in the separation of various compounds by means of the HPLC, SFC, and CEC methods follow.

Anti-Bacterial Agents↗
PubMed1992

[A mid-infrared spectra study of a series of benzocrown ether and macrocyclic polyether diester].

With a Nicolet 20 SX B Fourier Transform infrared spectrometer, the mid-infrared spectra in region of 4000-400 cm-1 were observed for a series of benzocrown ether and macrocyclic polyether diester. A difference in the wavelength of absorption of the ether bond was found between benzocrown ether and macrocyclic polyether diester. The wavelength of absorption of the ether bond of the compounds I-IV moved down about 25 cm-1, as compared with that of the compounds V-IX.

Ethers, Cyclic↗
PubMedDate not supplied

Long-term biodistribution in tumored mice of murine and chimeric B72.3-IgG antibody radiolabeled with 114mIn via both DTPA and a macrocyclic chelator.

To assess the possibilities of using 114mIn as a therapeutic agent, the long-term biodistribution of 114mIn was studied, in tumor-bearing nude mice, after injection of labeled monoclonal antibody (MoAb) B72.3 IgG, either DTPA-coupled murine, DTPA-coupled chimeric, or macrocycle-coupled chimeric antibody. Although the biodistributions in all cases were similar, there were important differences. The use of DTPA-coupled chimeric antibody led to higher concentrations of radioactivity in tumor, and to lower concentrations in liver and bone, as compared to DTPA-coupled murine antibody. The use of macrocycle-coupled chimeric antibody led to higher concentrations of radioactivity in the liver and in bone as compared to the DTPA-coupled chimeric antibody. However, in this case there were no significant differences in tumor uptake or clearance. Radiation doses were calculated based on the organ retention and by neglecting source-to-target contributions. Radiation dose distribution was marginally favorable for therapy in the group injected with DTPA-coupled chimeric antibody.

Animals↗
PubMed2005

HPLC separation of enantiomers of some potential beta-blockers of the aryloxyaminopropanol type using macrocyclic antibiotic chiral stationary phases. Studies of the mechanism of enantioseparation, Part XI.

The macrocyclic antibiotic type chiral stationary phases based on native vancomycin, teicoplanin and teicoplanin aglycone (Chirobiotic V, Chirobiotic T and Chirobiotic TAG) were used for the HPLC separation of enantiomers of potential beta-blockers of the aryloxyaminopropanol type with a morpholino moiety in the hydrophilic part of the molecule. The chromatographic results presented include: retention, separation and resolution factors along with the enantioselective free energy difference corresponding to the separation of the enantiomers. Comparison of the results obtained on the three macrocyclic chiral stationary phases showed that in most cases the teicoplanin aglycone is responsible for enantioseparation of morpholino derivatives. By application of these chiral stationary phase highest resolution factors were achieved with a polar organic mobile phase system.

Adrenergic beta-Antagonists↗
PubMed1978

Induction of plasminogen activator in cultured cells by macrocyclic plant diterpene esters and other agents related to tumor promotion.

In vitro systems that are responsive to tumor-promoting agents may facilitate the identification of such agents and the analysis of their mode of action. We have previously reported that the potent tumor promoter phorbol-12-myristate-13-acetate induces the synthesis of the enzyme plasminogen activator in cultured chick embryo fibroblasts. We have, therefore, tested various compounds for their ability to induce plasminogen activator in chicken embryo fibroblasts. Among these, phorbol esters and other macrocyclic diterpene esters isolated from species of the families Euphorbiaceae and Thymelaeaceae were potent inducers of plasminogen activator. These compounds maximally induced enzyme to the same levels, although they differed in their relative molar potencies. Structural requirements for in vitro activity paralleled the requirements for activity in vivo. These results indicate that induction of plasminogen activator is a useful marker for the biologically active macrocyclic diterpene esters. On the other hand, tumor-promoting agents such as anthralin, cantharidin, Tween 60, and tobacco leaf extract failed to induce plasminogen activator.

Cells, Cultured↗
PubMed1977

Cytotoxic activity of macrocyclic metabolites from fungi.

The cytotoxic effect of 7 macrocyclic fungal metabolites on HeLa cells has been determined. The authors noted great differences in the cytotoxic activity of the substances investigated. Least effective had proved the metabolites curvularin and zearalenone which kept exhibiting ED50 at a concentration of 2 X 10(-4)M and at a concentration of 7.5 X 10(-5)M respectively, whereas the most effective cyanein and monorden gave rise to 50% inhibition of multiplication of HeLa cells at a thousandfold lower concentration than zearalenone. Cytochalasins A, B and D brought about 50% inhibition of proliferation of HeLa cells at concentrations of the same order, with ED50 ranging between 1.2-2.1 X 10(-6)M. The different biological activity of the studied macrocyclic fungal metabolites is discussed in connection with their chemical structure.

Cell Division↗
PubMed2006

Radanamycin, a macrocyclic chimera of radicicol and geldanamycin.

Radicicol and geldanamycin are potent inhibitors of the Hsp90 protein folding machinery, which is an emerging target for the development of cancer chemotherapeutics. However, radicicol is inactive in vivo and geldanamycin suffers from its redox-active behavior that produces toxicity unrelated to Hsp90 inhibition. It was proposed that a chimeric molecule containing the resorcinol ring of radicicol and the quinone of geldanamycin could provide an opportunity to elucidate structure-activity relationships for both natural products and serve as a starting point for the development of more potent inhibitors. Synthesis of the macrocyclic chimera named radanamycin is reported along with the biological activity exhibited by this compound in MCF-7 breast cancer cells.

Benzoquinones↗
PubMed2026

High-affinity, structure-validated and selective macrocyclic peptide tools for chemical biology studies of Huntingtin.

Huntington's disease (HD) is a fatal neurodegenerative disorder caused by a Cytosine-Adenosine-Guanine (CAG) repeat expansion in the Huntingtin (HTT) gene, with no disease-modifying therapies currently available. The precise molecular function of the HTT protein is unclear, and the lack of selective chemical tools has limited functional studies. We have identified and characterized macrocyclic peptide binders targeting HTT. These binders exhibit low-nanomolar affinity in vitro and engage distinct HTT and HTT-HAP40 interfaces, as revealed by hydrogen-deuterium exchange mass spectrometry and cryoelectron microscopy. Chemoproteomics confirmed selective binding in cell extracts from wildtype but not HTT-null cell lines. HAP40 consistently and stoichiometrically copurified with HTT across cell lines, including with HTT variants containing different CAG repeat lengths, highlighting the broad presence of the HTT-HAP40 complex.

Huntingtin Protein↗
PubMed2006

Synthesis and characterization of a new macrocyclic copper(II) complex with an N-glycosidic pendant arm: in vitro cytotoxicity and binding studies with calf-thymus DNA.

The new macrocyclic complex 2-amino-2-deoxy-N-[2-(1,3,5,8,11-pentaazacyclotridecan-3-yl)ethyl]-beta-D-glucopyranosylamine copper(II) dichloride (1a) was prepared and thoroughly characterized by various techniques. Molar-conductance measurements showed that 1a (and its Ni analogue 1b) are ionic in nature. On the basis of spectroscopic data, both complexes were assigned a square-planar geometry, and found to be highly stabile and hydrolytically robust in H2O over a wide range of pH, as confirmed by cyclic voltammetry (CV). The Cu(II) complex 1a was found to bind to CT-DNA, with a binding constant Kb of 2.4x10(3) M(-1), as derived by UV/VIS titration, and confirmed by CV, circular dichroism (CD), and viscosity measurements. DNA binding seems to occur mostly via H-bonding. In an in vitro antitumor MTT assay, 1a exhibited significant anticancer activity against the SY5Y and PC-12 cell lines, with an estimated IC50 value in the micromolar range for SYSY, similar to the standard drug 5-fluorouracil.

Animals↗
PubMed2005

Ring-closing metathesis of C-terminal allylglycine residues with an N-terminal beta-vinyl-substituted phosphotyrosyl mimetic as an approach to novel Grb2 SH2 domain-binding macrocycles.

Ring-closing metathesis (RCM) of peptides often requires insertion of allylglycines at the intended sites of ring juncture, which can result in the displacement of residues that are needed for biological activity. This type of side-chain deletion can be avoided by appending beta-vinyl substituents onto the parent residues at the intended sites of ring juncture, thereby effectively converting them into functionalized allylglycine equivalents. Such an approach has been previously applied in modified form to growth-factor receptor bound 2 (Grb2) SH2 domain-binding peptides by using an N-terminal beta-vinyl-functionalized phosphotyrosyl mimetic and C-terminal 2-allyl-3-aryl-1-propanamides that lacked the alpha-carboxyl portion of allylglycine residues. These C-terminal moieties involved lengthy synthesis and once prepared, required an individual total synthesis of each final macrocycle. Work reported herein significantly enhances the versatility of the original approach through the use of C-terminal allylglycine amides that can be prepared from commercially available L- and D-allylglycines and suitable amines. This methodology could be generally useful where macrocylization is desired with maintenance of functionality at a site of ring juncture.

Adaptor Proteins, Signal Transducing↗
PubMed2006

An examination of the binding behavior of histidine-containing peptides with immobilized metal complexes derived from the macrocyclic ligand, 1,4,7-triazacyclononane.

In this study, two different experimental approaches have been employed to examine the binding behavior of histidine-containing peptides with metal ion complexes derived from the macrocyclic ligand 1,4,7-triazacyclononane (tacn). Firstly, a molecular modeling approach has been employed to derive the strain energies for test peptide sequences that have a predicted propensity to readily adopt an alpha-helical conformation. To this end, binuclear metal complexes were examined with peptides containing two histidine residues in different locations in a pair of peptides of the same composition but different sequence. These modeling results indicate that there are no energetic constraints for two-point binding to occur with dicopper(II) binuclear complexes when two histidine residues are appropriately placed in an alpha-helical conformation. Secondly, binding experiments were carried out to establish the effect of one or more histidine residues within a peptide sequence on the affinity of a peptide for these Cu(II)-tacn derived binuclear complexes when immobilized onto a chromatographic support material. The results confirm that for all chelating systems, higher affinity is achieved as the histidine number in the peptide structure increases, although the relative location of the histidine residues in these small peptides did not introduce a significant constraint to the conformation on interacting with the immobilized Cu(II) binuclear complexes.

Binding Sites↗
PubMed2005

Astonishing diversity of natural surfactants: 2. Polyether glycosidic ionophores and macrocyclic glycosides.

Polyether glycosidic ionophores and macrocyclic glycosides are of great interest, especially for the medicinal and pharmaceutical industries. These biologically active natural surfactants are good prospects for the future chemical preparation of compounds useful as antibiotics, anticancer agents, or in industry. More than 300 interesting and unusual natural surfactants are described in this review article, including their chemical structures and biological activities.

Anti-Bacterial Agents↗
PubMed2006

Electrochemical detection of scDNA cleavage in the presence of macrocyclic hexaaza-copper(II) complex.

The hexaaza macrocyclic copper(II) complex Cu(II)L(L=1,8-Dihydroxyethyl-1,3,6,8,10,13-hexaazacyclotetradecane), which has octahedral structure similar to some natural complexes, is synthesized and purified. In this study, oxidative breakage DNA by the reaction of Cu(II)L with H2O2 and ascorbate has been investigated by gel electrophoresis experiments. In electrochemical experiments, the on scDNA-modified glassy carbon electrode(GCE) is cleaved by the Cu(II)L and redox changing of the metal catalyst without adding any other reagents. Above all, the need for concentration of scDNA is much lower than that of gel electrophoresis experiments and the process of the performance is easy. Furthermore, Cyclic Voltammetry (CV) and A.C. Impedance, which are performed to monitor scDNA cleavage at the scDNA-modified glassy carbon electrode (GCE), are fast, simple and highly efficient. The mechanism of the damage can be suggested: Fenton.

Ascorbic Acid↗
PubMed2005

Dinuclear macrocyclic polyamine zinc(II) complexes linked with flexible spacers: synthesis, characterization, and DNA cleavage.

Dinuclear macrocyclic polyamine zinc(II) complexes, which have two cyclen groups linked by flexible spacers, have been synthesized as DNA cleavage agents. The structures of these new dinuclear complexes are consistent with the data obtained from elemental analysis, MS and 1H NMR spectroscopy. The catalytic activity of these dinuclear complexes on DNA cleavage was studied. The results showed that the dinuclear zinc(II) complexes can catalyze the cleavage of supercoiled DNA (pUC 19 plasmid DNA) (Form I) under physiological conditions to produce selectively nicked DNA (Form II).

DNA↗
PubMed2006

Chiral multinuclear macrocyclic polyamine complexes: synthesis, characterization and their interaction with plasmid DNA.

A series of multinuclear macrocyclic polyamine metal (Zn(2+), Cu(2+), Co(2+)) complexes containing chiral dipeptide linkage were synthesized and used as artificial nuclease enzyme model. The interaction between the complexes and plasmid DNA (pUC19) was studied, and the results revealed that these complexes could act as powerful catalysts for the cleavage of plasmid DNA under physiological conditions.

Catalysis↗
PubMed2004

Macrocyclic ketone analogues of halichondrin B.

Structurally simplified macrocyclic ketone analogues of halichondrin B were prepared by total synthesis and found to retain the potent cell growth inhibitory activity in vitro, stability in mouse serum, and in vivo efficacy of the natural product.

Animals↗