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At least 649 records · Page 36Linked to original sources
PubMed1998

Anti-HIV activity and mechanism of action of macrocyclic diamide SRR-SB3.

The importance of cyclic compounds as anti-cancer and anti-viral agents has been recognized for some time. We have studied a series of macrocyclic amide derivatives for activity against HIV infection of T lymphocytes in-vitro. Compounds containing aromatic rings and sulphur atoms were generally active, however the selectivity was greatly enhanced when two benzene rings were bridged by a disulphide linkage to produce 7-methyl-6,7,8,9-tetrahydrodibenzo[c,k][1,2,6,9]-dithiadiazacyc lododecine-5,10-dione (SRR-SB3). This compound was studied in detail with different cell and virus infections including macrophages and chronically infected H9 cells. It was active with an EC50 (the dose affording 50% inhibition of infection) of 0.05-01 microg mL(-1) and a TC50 (concentration reducing uninfected cell growth by 50%) of 50 microg mL(-1). The compound did not inhibit protease, but seemed to act by inhibiting maturation of progeny virus, by interfering with precursor protein processing. It was synergistic with AZT (3'-azido-3'-deoxythymidine; zidovudine) when tested in-vitro. The unusual mode of action and potent anti-HIV activity in T lymphocytes and macrophages makes this compound a potential candidate for clinical trials.

Anti-HIV Agents↗
PubMed2002

Separation of chiral sulfoxides by liquid chromatography using macrocyclic glycopeptide chiral stationary phases.

A set of 42 chiral compounds containing stereogenic sulfur was prepared. There were 31 chiral sulfoxide compounds, three tosylated sulfilimines and eight sulfinate esters. The separations were done using five different macrocyclic glycopeptide chiral stationary phases (CSPs), namely ristocetin A, teicoplanin, teicoplanin aglycone (TAG), vancomycin and vancomycin aglycone (VAG) and seven eluents, three normal-phase mobile phases, two reversed phases and two polar organic mobile phases. Altogether the macrocyclic glycopeptide CSPs were able to separate the whole set of the 34 sulfoxide enantiomers and tosylated derivatives. Five of the eight sulfinate esters were also separated. The teicoplanin and TAG CSPs were the most effective CSPs able to resolve 35 and 33 of the 42 compounds. The three other CSPs each were able to resolve more than 27 compounds. The normal-phase mode was the most effective followed by the reversed-phase mode with methanol-water mobile phases. Few of these compounds could be separated in the polar organic mode with 100% methanol mobile phases. Acetonitrile was also not a good solvent for the resolution of enantiomers of sulfur-containing compounds, neither in the reversed-phase nor in the polar organic mode. The structure of the chiral molecules was compared to the enantioselectivity factors obtained with the teicoplanin and TAG CSP. It is shown that the polarity, volume and shape of the sulfoxide substituents influence the solute enantioselectivity factor. Changing the oxidation state of the sulfur atom from sulfoxides to sulfinate esters is detrimental to the compound's enantioselectivity. The enantiomeric retention order on the teicoplanin and TAG CSPs was very consistent: the (S)-(+)-sulfoxide enantiomer was always the less retained enantiomer. In contrast, the (R)-(-)-enantiomer was less retained by the ristocetin A, vancomycin and vancomycin aglycone columns, showing the complementarity of these CSPs. The macrocyclic glycopeptide CSPs provided broad selectivity and effective separations of chiral sulfoxides.

Chromatography, Liquid↗
PubMed2003

Self-assembly of coordination polymers from AgX (X = SbF(6)(-), PF(6)(-), and CF(3)SO(3)(-)) and oxadiazole-containing ligands.

The coordination chemistry of the oxadiazole-containing rigid bidentate ligands 2,5-bis(4-pyridyl)-1,3,4-oxadiazole (L1), 2,5-bis(3-pyridyl)-1,3,4-oxadiazole (L2), and 2,5-bis(3-aminophenyl)-1,3,4-oxadiazole (L3) with inorganic Ag(I) salts has been investigated. Four new coordination polymers (1, 2, 3, and 5) and one new bimetallic macrocyclic supramolecular complex (4) were synthesized from solution reactions of L1-L3 with inorganic Ag(I) salts, respectively. Compounds [[Ag(L1)]SbF(6)](n) (1) (1, monoclinic, P2(1)/c, a = 6.6846(4) A, b = 27.1113(15) A, c = 8.6802(5) A, beta = 94.1080(10) degrees, Z = 4) and [[Ag(L1)]PF(6)](n) (2) (2, monoclinic, P2(1)/c, a = 6.6753(3) A, b = 27.2824(14) A, c = 8.2932(4) A, beta = 94.6030(10) degrees, Z = 4) were obtained from the reactions of L1 with AgSbF(6) and AgPF(6) in a CH(2)Cl(2)/CH(3)OH mixed solvent system, respectively. Compounds 1 and 2 are isostructural and feature a novel two-dimensional zeolite-like net with two different individual rings. [[Ag(L2)]SbF(6)](n) (3) (3, monoclinic, P2(1)/c, a = 5.5677(3) A, b = 17.3378(9) A, c = 15.6640(8) A, beta = 94.4100(10) degrees, Z = 2) and [Ag(2)(L2)(2)](SbF(6))(2) (4) (4, triclinic, P1, a = 8.7221(5) A, b = 9.2008(6) A, c = 10.7686(7) A, alpha = 70.6270(10) degrees, beta = 75.7670(10) degrees, gamma = 73.7560(10) degrees, Z = 1) were obtained from one-pot reaction of L2 with AgSbF(6) in a CH(2)Cl(2)/CH(3)OH mixed solvent system. Compound 3 features a one-dimensional chain pattern, while compound 4 adopts a novel bimetallic macrocyclic structural motif which consists of Ag(2)(L2)(2) ringlike units (crystallographic dimensions, 8.06 x 7.42 A(2)). [[Ag(L3)]SO(3)CF(3)](n) (5) is generated from L3 and AgSO(3)CF(3) in a CH(2)Cl(2)/CH(3)OH mixed solvent system and crystallizes in the unusual space group Pbcn, with a = 9.8861(5) A, b = 20.2580(10) A, c = 17.5517(8) A, Z = 8. It adopts novel two-dimensional sheets that are cross-linked to each other by strong interlayer N-H...O hydrogen bonding interactions into a novel H-bonded three-dimensional network.

Journal Article↗
PubMed2006

Catecholase activity of a copper(II) complex with a macrocyclic ligand: unraveling catalytic mechanisms.

We report the structure, properties and a mechanism for the catecholase activity of a tetranuclear carbonato-bridged copper(II) cluster with the macrocyclic ligand [22]pr4pz (9,22-dipropyl-1,4,9,14,17,22,27,28,29, 30-decaazapentacyclo[22.2.1.1(4,7).1(11,14). 1(17,20)]triacontane-5,7(28),11(29),12,18, 20(30),24(27),25-octaene). In this complex, two copper ions within a macrocyclic unit are bridged by a carbonate anion, which further connects two macrocyclic units together. Magnetic susceptibility studies have shown the existence of a ferromagnetic interaction between the two copper ions within one macrocyclic ring, and a weak antiferromagnetic interaction between the two neighboring copper ions of two different macrocyclic units. The tetranuclear complex was found to be the major compound present in solution at high concentration levels, but its dissociation into two dinuclear units occurs upon dilution. The dinuclear complex catalyzes the oxidation of 3,5-di-tert-butylcatechol to the respective quinone in methanol by two different pathways, one proceeding via the formation of semiquinone species with the subsequent production of dihydrogen peroxide as a byproduct, and another proceeding via the two-electron reduction of the dicopper(II) center by the substrate, with two molecules of quinone and one molecule of water generated per one catalytic cycle. The occurrence of the first pathway was, however, found to cease shortly after the beginning of the catalytic reaction. The influence of hydrogen peroxide and di-tert-butyl-o-benzoquinone on the catalytic mechanism has been investigated. The crystal structures of the free ligand and the reduced dicopper(I) complex, as well as the electrochemical properties of both the Cu(II) and the Cu(I) complexes are also reported.

Catalysis↗
PubMed2005

Regioselective N-functionalization of tetraazacycloalkanes.

[reaction: see text] Bisaminal type compounds obtained by condensation of pyruvic aldehyde with the suitable open-chain tetraamine followed by cyclization with either dibromoethane or dibromopropane can be regioselectively quaternized by a wide range of alkylating agents. Removal of the bisaminal bridge yields the monosubstituted tetraazamacrocycle or bismacrocycle. Further functionalization allows the preparation of bifunctional ligands or trisubstituted macrocycles. The structure of six compounds was solved by X-ray diffraction, and the unexpected results are rationalized according to the molecular modeling calculations.

Journal Article↗
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↗
PubMed1996

Synthetic Routes to a Constrained Ring Analog of Didemnin B.

The didemnin class of biologically active cyclodepsipeptides, isolated from a marine tunicate, has shown antitumor, antiviral, and immunosuppressive activities. Synthetic studies were undertaken to prepare a modified analog of one of the most potent congeners, didemnin B (1). The side chain of the isostatine unit was tethered into the macrocycle viaa cyclohexane ring in order to provide a more rigid conformation and determine the importance of this unit in bioactive compounds. This modification created a new macrocycle core and generated a diastereomeric mixture of a constrained analog of didemnin B (2).

Journal Article↗
PubMed2005

Cyclen based bis-macrocyclic ligands as phosphates receptors. A potentiometric and NMR study.

The host-guest interaction between orthophosphate, pyrophosphate and triphosphate anions and four cyclen based bis-macrocycles ligands possessing ortho-(BOC), meta-(BMC), para-xylenyl (BPC) or 2,6-pyridinyl (BPyC) linker was investigated by potentiometric measurements and NMR spectroscopy. Each ligand gave protonated species in aqueous solution that further formed ternary complexes after binding with anions; these complexes were analyzed as a result of hydrogen bond formation and Coulombic attraction between the organic host and the inorganic guest. The equilibrium constants for all the detected species are reported and the selectivity, illustrated with species distribution diagrams, is discussed. The results unambiguously showed the importance of the distance between the two cyclen cores and underlined, especially for the triphosphate species, the contribution of the nitrogen atom of the pyridinyl spacer as a supplementary anchoring point in acidic medium.

Anions↗
PubMed1994

Synthetic polyamines stimulate in vitro transcription by T7 RNA polymerase.

The influence of nine synthetic polyamines on in vitro transcription with T7 RNA polymerase has been studied. The compounds used were linear or macrocyclic tetra- and hexaamine, varying in their size, shape and number of protonated groups. Their effect was tested on different types of templates, all presenting the T7 RNA promoter in a double-stranded form followed by sequences encoding short transcripts (25 to 35-mers) either on single- or double-stranded synthetic oligodeoxyribonucleotides. All polyamines used stimulate transcription of both types of templates at levels dependent on their size, shape, protonation degree, and concentration. For each compound, an optimal concentration could be defined; above this concentration, transcription inhibition occurred. Highest stimulation (up to 12-fold) was obtained by the largest cyclic compound called [38]N6C10.

Bacteriophage T7↗
PubMed2005

Magic ring catenation by olefin metathesis.

[reaction: see text]. Olefin metathesis has been employed in the efficient syntheses of a [2]catenane with the templation being provided by the recognition between a secondary ammonium ion and a crown ether. In one approach, a crown ether precursor has been clipped around an NH2+ center situated in a macrocyclic ring, yielding the mechanically interlocked compound. In the other approach, the reversible nature of olefin metathesis allows for a magic ring synthesis to occur wherein two free macrocycles can be employed as the stationary materials, leading to the formation of the same [2]catenane.

Journal Article↗
PubMed2000

A new approach to macrocyclization via alkene formation in catalytic diazo decomposition. Synthesis of patulolides A and B.

[reaction: see text] Effective synthetic uses of bisdiazocarbonyl compounds for the selective construction of diverse macrocycles, including the synthesis of patulolides A and B, by catalytic "carbene dimer" formation are reported. Control of stereochemistry and efficient methods for product isomerization or kinetic isomer differentiation have been achieved.

Alkenes↗
PubMed2004

Aureoverticillactam, a novel 22-atom macrocyclic lactam from the marine actinomycete Streptomyces aureoverticillatus.

During the course of our screening program designed to discover novel anticancer and anti-infective agents from marine microorganisms, a strain of Streptomyces aureoverticillatus (NPS001583) isolated from a marine sediment was found to produce a novel macrocyclic lactam with cytotoxicity against various tumor cell lines. Using extensive MS, UV, and NMR spectral analyses, the structure has been established as compound 1, aureoverticillactam, a 22-atom macrocyclic lactam incorporating both triene and tetraene conjugated olefins.

Actinobacteria↗
PubMed1999

Bis-macrocyclic Ligands with Two Ferrocenyl End Groups, and Their Tetranuclear Dicopper(I) Compounds.

A series of bismacrocyclic ligands with two ferrocenyl groups, exo/endo-1,1':1' ',1' "-[1,2,4,5-tetrakis(5-aza-2-thiahexa-5-enyl)benzene]bisferrocene (exo/endo-FeBeFe), 1,1':1' ',1' "-[1,2:1',2'-tetrakis(5-aza-2-thiahexa-5-enyl)ethene]bisferrocene (1,2-FeEnFe), 1,1':1' ',1' "-[1,1':2,2'-tetrakis(5-aza-2-thiahexa-5-enyl)ethene]bisferrocene (1,1-FeEnFe), 1,1':1' ',1' "-[tetrakis(5-aza-2-thiahexa-5-enyl)methane]bisferrocene (FeMeFe), and their dicopper(I) compounds have been synthesized and characterized (electrochemistry, IR, NMR and Mössbauer spectroscopy). The molecular structure of endo-FeBeFe has been determined by X-ray structure analysis and the copper(I)-induced discrimination of the exo- and endo-isomers of FeBeFe has been investigated by (1)H NMR spectroscopy. The interaction between copper and iron in the tetranuclear compounds is discussed on the basis of the electrochemical and spectroscopic data.

Journal Article↗
PubMed2001

Solution structure of the squash trypsin inhibitor MCoTI-II. A new family for cyclic knottins.

The "knottin" fold is a stable cysteine-rich scaffold, in which one disulfide crosses the macrocycle made by two other disulfides and the connecting backbone segments. This scaffold is found in several protein families with no evolutionary relationships. In the past few years, several homologous peptides from the Rubiaceae and Violaceae families were shown to define a new structural family based on macrocyclic knottin fold. We recently isolated from Momordica cochinchinensis seeds the first known macrocyclic squash trypsin inhibitors. These compounds are the first members of a new family of cyclic knottins. In this paper, we present NMR structural studies of one of them, MCoTI-II, and of a beta-Asp rearranged form, MCoTI-IIb. Both compounds display similar and well-defined conformations. These cyclic squash inhibitors share a similar conformation with noncyclic squash inhibitors such as CPTI-II, and it is postulated that the main effect of the cyclization is a reduced sensitivity to exo-proteases. On the contrary, clear differences were detected with the three-dimensional structures of other known cyclic knottins, i.e., kalata B1 or circulin A. The two-disulfide cystine-stabilized beta-sheet motif [Heitz et al. (1999) Biochemistry 38, 10615-10625] is conserved in the two families, whereas in the C-to-N linker, one disulfide bridge and one loop are differently located. The molecular surface of MCoTI-II is almost entirely charged in contrast to circulin A that displays a well-marked amphiphilic character. These differences might explain why the isolated macrocyclic squash inhibitors from M. cochinchinensis display no significant antibacterial activity, whereas circulins and kalata B1 do.

Amino Acid Sequence↗
PubMed2006

Aza-beta3-cyclohexapeptides: pseudopeptidic macrocycles with interesting conformational and configurational properties slow pyramidal nitrogen inversion in 24-membered rings!

Among pseudopeptidic foldamers, aza-beta3-peptides have the unique property to possess nitrogen stereocenters instead of carbon stereocenters. As the result of pyramidal inversion at N(alpha)-atoms along the backbone, they behave as a set of C8-based secondary structures in equilibrium. This structural modulation is exploited here to prepare 24-membered macrocycles with great efficiency. Both crystal structures and spectroscopic data establish that aza-beta3-cyclohexapeptides adopt a highly organized conformation where the relative configuration of chiral nitrogen atoms is alternated. This makes them an interesting scaffold as the stereocontrol occurs spontaneously through the cyclization. These compounds reveal an unprecedented slow pyramidal nitrogen inversion in macrocycles. Pyramidal ground state stabilization, hindered rotation, steric crowding, and H-bond cooperativity are proposed to participate in this striking phenomenon. The equilibrium between invertomers of aza-beta3-cyclohexapeptides is reminiscent of the interchange between the two chair forms of cyclohexane.

Aza Compounds↗
PubMed2005

Novel copper(II) homobinuclear macrocyclic complexes: cyclic voltammetry, biological properties and spectral studies.

A series of five new copper(II) macrocyclic complexes have been synthesized by template condensation. The bonding and stereochemistry of the complexes have been characterized by elemental analysis, molar conductance, magnetic susceptibility, IR, UV-visible, EPR spectral studies and electrochemical properties. g-Values are calculated for all of the complexes in polycrystalline form as well as in DMSO solution. The magnetic and spectral data indicate square planar geometry for all the complexes. Cyclic voltammograms for all the complexes are similar and involve two quasi-reversible redox processes. Cu(II)Cu(II)<=>Cu(II)Cu(I)<=>Cu(I)Cu(I). Their biological properties have also been studied. The macrocyclic complexes show more anti-bacterial than controlled one. The anti-bacterial activities of the compounds were tested against Streptococcus fecalis and Escherichia coli with different concentrations.

Anti-Bacterial Agents↗