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At least 703 records · Page 39Linked to original sources
PubMed2005

Novel C2-C3' N-peptide linked macrocyclic taxoids. Part 1: Synthesis and biological activities of docetaxel analogues with a peptide side chain at C3'.

A series of novel docetaxel analogues possessing a peptide side chain at the C3'-N position was synthesized. These compounds were designed to mimic a region of the alpha-tubulin loop that is equivalent to the paclitaxel binding pocket in beta-tubulin. Eight new peptidic taxoids were obtained and evaluated as inhibitors of microtubule disassembly, as well as for their cytotoxicity.

Animals↗
PubMed2004

Synthesis and properties of new bolaform and macrocyclic galactose-based surfactants obtained by olefin metathesis.

A series of galactose-based surfactants with various structures likely to display new interesting properties were synthesized. Four monocatenary surfactants were elaborated by microwave-assisted galactosylation of undecanol or 10-undecenol. These compounds were slightly soluble in water. Their tensioactive properties were determined at 45 degrees C. Olefin metathesis was used to synthesize the two single-chain bolaforms from undec-10-enyl galactopyranosides; two pseudomacrocyclic bolaforms were prepared by grafting two carbamates at O-4 and O-4' sugar positions of the single-chain bolaforms. These four surfactants are insoluble in water and undergo monolayer compression. Cyclization of these bolaforms by olefin metathesis led to macrocyclic surfactant analogues of archaeobacterial membrane components.

Alkenes↗
PubMed2005

[Interaction of cucurbit[ n ]urils and quinoline or its derivatives].

The structures and fluorescence characteristics of cucurbit[n = 6-8]urils with quinoline, isoquinoline and 7-methyl quinoline have been investigated by fluorescence spectrophotometry. Compared to NMR techniques, thefluorometric analysis methodrevealed that there are not only obvious interactions of quinoline or its derivates and cucurbit[7]uril, but also interactions of quinoline or its derivates and cucurbit[6]uril or cucurbit[8]uril which can not be observed by using 1H NMR technique. The experimental results also revealed that quinoline, isoquinoline and 7-methyl quinoline were included by cucurbit[6-8]uril with different ratios. There could be three kinds of interactions of cucurbit[n]urils and the guests: (a) cavity interaction, including hydrophobic forces and Van der Waals contact forces between macrocycles and cages; (b) portals ion-dipole interaction, or electrostatic interaction of the positive charge of the guests and the carbonyl groups at the portals of cucurbit[n]uril; (c) size interaction which requires the size of the guest matching a cucurbit[n]uril.

Bridged-Ring Compounds↗
PubMed1998

Macrocyclic diterpenoids from Euphorbia semiperfoliata.

In addition to known compounds, the aerial parts of E. semiperfoliata afforded an abietanolide (3), 13 jatrophane polyesters (4-9, 12, 14-19), two 4-deoxyphorbol diesters (23, 24), and a pair of epimeric diterpenes (21, 22) with a novel carbon skeleton, which was named euphoperfoliane. Structures were determined by spectroscopic analysis, and the main conformational features of jatropha-6(17),11-dienes are discussed in detail. The obtained isolation yield of several jatrophanes was unprecedented within the spurges (Euphorbia spp.), making E. semiperfoliata a unique source of macrocyclic diterpenoids.

Carbohydrate Sequence↗
PubMed2004

DNA-templated organic synthesis and selection of a library of macrocycles.

The translation of nucleic acid libraries into corresponding synthetic compounds would enable selection and amplification principles to be applied to man-made molecules. We used multistep DNA-templated organic synthesis to translate libraries of DNA sequences, each containing three "codons," into libraries of sequence-programmed synthetic small-molecule macrocycles. The resulting DNA-macrocycle conjugates were subjected to in vitro selections for protein affinity. The identity of a single macrocycle possessing known target protein affinity was inferred through the sequence of the amplified DNA template surviving the selection. This work represents the translation, selection, and amplification of libraries of nucleic acids encoding synthetic small molecules rather than biological macromolecules.

Amides↗
PubMed2002

Synthesis and membrane activity of a bis(metacyclophane)bolaamphiphile.

The synthesis of macrocyclic tetraesters from 5-substituted isophthalic acids and 1,8-octane diol gave macrocylic metacyclophanes with the axially symmetric positions differentially protected. Dimer bis(metacyclophane)bolaamphiphiles proved to be extremely insoluble, but one derivative was shown to have significant membrane activity. Very high continuous conductance and the formation of discrete single-ion channels were both observed, depending on how the compound was incorporated into the bilayer membrane.

Biological Transport↗
PubMed2005

Induction of neutral endopeptidase activity in PC-3 cells by an aqueous extract of Epilobium angustifolium L. and oenothein B.

An aqueous extract of Epilobium angustifolium and its main compound oenothein B (OeB), a dimeric macrocyclic ellagitannin, are specifically able to induce the neutral endopeptidase (NEP) in prostate cancer cells. The angiotensin-converting enzyme (ACE) is not influenced. Additionally, a weak but statistically significant inhibition of cell proliferation is observed. Simultaneous treatment of the cells with arabinosylcytosine and the extract as well as the OeB, leads to an additional enhancement of NEP activity. Taking into account the role of this peptidase in prostate cancer progression, our results might offer a pharmacological explanation for the use of Epilobium in folk medicine.

Cell Line, Tumor↗
PubMed2002

A glutamate-gated chloride channel subunit from Haemonchus contortus: expression in a mammalian cell line, ligand binding, and modulation of anthelmintic binding by glutamate.

Glutamate-gated chloride channels (GluCls) are inhibitory ion channels that are sensitive to the antiparasitic drugs ivermectin (IVM) and moxidectin (MOX). We have transiently transfected COS-7 cells with a subunit of a GluCl (HcGluCla) from the parasitic nematode Haemonchus contortus. This subunit bound [3H]-IVM and [3H]-MOX with K(d) values of 0.11+/-0.021 and 0.18+/-0.02nM, respectively. Displacement analysis revealed that IVM and MOX bind to the same site on HcGluCla and that this site is likely distinct from the glutamate binding site. Glutamate was found to be an allosteric modulator of [3H]-MOX and [3H]-IVM binding and increased the affinity of [3H]-MOX for HcGluCla by more than 50% and that of [3H]-IVM by more than 7-fold. These results point to both similarities and differences in the interactions of IVM and MOX with the GluCl. Aspartate, which is structurally similar to glutamate, had little or no effect on [3H]-IVM and [3H]-MOX binding, suggesting that this ligand does not induce the conformational change necessary to potentiate macrocyclic lactone binding. These results also indicate that it may be possible to enhance the efficacy of macrocyclic lactone anthelmintics by administering these compounds with ligands acting allosterically to enhance their binding.

Animals↗
PubMed2001

Discovery of selective hydroxamic acid inhibitors of tumor necrosis factor-alpha converting enzyme.

Modification of the P(1)' substituent of macrocyclic matrix metalloproteinase (MMP) inhibitors provided compounds that are selective for inhibition of tumor necrosis factor-alpha converting enzyme (TACE) over MMP-1 and MMP-2. Several analogues potently inhibited the release of TNF-alpha in a THP-1 cellular assay. Compounds containing a trimethoxyphenyl group in the P(1)' substituent demonstrated TACE selectivity across several series of hydroxamate-based inhibitors.

ADAM Proteins↗
PubMed1993

Heterocyclic lactam derivatives as dual angiotensin converting enzyme and neutral endopeptidase 24.11 inhibitors.

A series of 13- and 14-membered ring lactam derivatives 9a,b, 10, 11, and 12a-c was prepared from L-cysteine. Compounds 9a,b and 12a,b were tested in vitro for inhibition of neutral endopeptidase 24.11 (NEP) and angiotensin converting enzyme (ACE) inhibition. The structure-activity profile of the series is discussed. Compound 9b, a 13-membered ring macrocyclic lactam, had an NEP IC50 of 18 nM and an ACEIC50 of 12 nM in vitro and showed dual plasma inhibition after intravenous or oral administration.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2003

Synthesis and antitumor activity of novel O-carbamoylmethyloxime derivatives of radicicol.

Radicicol (1), a macrocyclic antifungal antibiotic, is the lead compound of a novel class of heat shock protein 90 (Hsp90) inhibitors that result in the inhibition or degradation of Hsp90-associated proteins, such as v-src and Raf-1 kinases. New O-carbamoylmethyloxime derivatives of 1 were synthesized and evaluated for their in vitro antiproliferative activities against v-src- and K-ras-transformed cells and for their inhibitory activity against v-src tyrosine kinase. O-(Piperidinocarbonyl)methyloxime 9b, one of the most potent of these derivatives, exhibited more potent antiproliferative activity than 1 and its hydroxime KF25706 (2) and had an IC(50) of 25 nM for the inhibition of v-src kinase activity. Compound 9b was also found to decrease the Raf-1 protein level of KNRK5.2 cells. Furthermore, compound 9b exhibited significant antitumor activity when tested against MX-1 and A431 xenografts in nude mice.

Animals↗
PubMed2005

[2.2]paracyclophane/dehydroannulene hybrids: probing the aromaticity of the dehydro[14]annulene framework.

The synthesis of [2.2]paracyclophane/dehydro[14]annulene hybrids 1 and 2 is reported. Comparison of the proton NMR spectra of 1 and 2 with their open precursors and with related model compounds reveals the pronounced effect of macrocycle formation upon the cyclophane protons H15/H16, which lie above the shielding cone of the diatropic [14]annulene moiety. [structure: see text]

Journal Article↗
PubMed2005

Tautomerization in naphthalenediimines: a keto-enamine Schiff base macrocycle.

[reaction: see text] A new [3 + 3] Schiff base macrocycle incorporating naphthalene groups has been prepared. By examination of its properties, X-ray crystallography of model compounds, and calculations, it has been determined that the macrocycle exists predominantly as the keto-enamine tautomer. This unexpected tautomerization presents an unusual hexaketo interior in the macrocycle.

Journal Article↗
PubMed1999

Clofibrate inhibits membrane trafficking to the Golgi complex and induces its retrograde movement to the endoplasmic reticulum.

Insights into the function of the Golgi complex have been provided by experiments performed with various inhibitors of membrane trafficking, such as the macrocyclic lactone brefeldin A (BFA), a compound that inhibits constitutive secretion, prevents the formation of coatomer-coated transport vesicles, and stimulates the retrograde movement of Golgi resident enzymes back to the ER. We show here that the structurally unrelated compound clofibrate, a peroxisome proliferator (PP) and hypolipidemic agent, also reversibly disrupts the morphological and functional integrity of the Golgi complex in a manner similar to BFA. In the presence of clofibrate, the forward transport of newly synthesized secretory proteins from the ER to the Golgi is dramatically inhibited. Moreover, clofibrate causes Golgi membranes to travel rapidly in a microtubule-dependent manner back to the ER, forming a hybrid ER-Golgi tubulovesicular membrane network. These affects appear to be independent of clofibrate's ability to stimulate the PP-activated receptor (PPAR) alpha pathway because other PPAR stimulators (DEHP, WY-14643) did not alter the Golgi complex or induce retrograde trafficking. These data suggest that PPAR alpha-independent, clofibrate-sensitive proteins participate in regulating Golgi-to-ER retrograde membrane transport, and, equally importantly, that clofibrate may be used as a pharmacological tool for investigating Golgi membrane dynamics.

Animals↗
PubMed1989

Ionophoretic activities of oligopeptide lactones and resin-glycosides in human erythrocytes.

Oligopeptide lactones (theonellapeptolides) isolated from the Okinawan marine sponge Theonella swinhoei and resin-glycosides (merremosides) from the tuber of an Indonesian medicinal plant Merremia mammosa were examined regarding their activities in transporting Na+, K+, and Ca++ ions into human erythrocytes. Each of these lactones, which had been shown, using a supported liquid membrane, to have an ionophoretic effect on the alkali metal ions, transported the ions to a different extent. The ion transporting activities of these compounds were completely lost when the macrocyclic lactone structures were cleaved by sodium methylate. Resin-glycosides with an additional branched glycosyl residue showed much greater ion transporting activities than those without it.

Erythrocytes↗
PubMed2004

Isolation of a new 15-membered macrocyclic glycolipid lactone, Cuscutic Resinoside a from the seeds of Cuscuta chinensis: a stimulator of breast cancer cell proliferation.

While searching for new estrogenic compounds from the plant kingdom, we investigated an extract of the seeds of Cuscuta chinensis (Convolvulaceae) which showed potency for stimulating MCF-7 cell proliferation. A novel resin glycoside, cuscutic resinoside A ( 6) was isolated along with five known compounds from the extract. The structure was deduced from its spectral data as (11 S)-hydroxyhexadecanoic acid 11- O-alpha- L-(4- O-2 R,3 R-nilylrhamnopyranosyl)-(1-->2)- O-alpha- L-rhamnopyranosyl-(1,2-lactone) forming a unique 15-membered macrocyclic lactone. The compound significantly stimulated not only MCF-7 cell proliferation but also T47D human breast cancer cells at a concentration of 10 microM. Along with cuscutamine ( 1) and kaempferol ( 4), 6 was tested in the transient luciferase reporter assay and was found to have different luciferase inducing activity characteristics from the other compounds. These results suggest that 6 stimulated cancer cell proliferation by a different mechanism from 1 and 4.

Breast Neoplasms↗
PubMed2004

Chiral polymers containing a carbohydrate moiety: synthesis.

This paper reports the preparation of poly(acetal-ethers) by two alternative synthetic pathways (alkaline and acid-catalyzed conditions). Polycondensations of methyl 2,3:4,6-di-O-salicylidene-alpha-D-mannopyranoside (3) (mixtures of endo-H and exo-H dioxolan-2-yl-diastereomers) with 1,4-dibromobutane (4) (method I a and I b) were performed in solvents (DMF, butyl acetate/DMF, DMSO) and were catalyzed by K2CO3/KI or KOH. A similar polymer (6) was formed by the reaction of methyl alpha-D-mannopyranoside (1) and 1,4-bis(2-formylphenoxy)butane (7), catalyzed by p-toluenesulfonic acid (method II). Regardless of conversion or initial comonomer feed ratios, the composition of the polycondensates depended on the reaction conditions, leading to the formation of macrocyclic [1 + 1] (5) and [2 + 2] compounds, which were macromolecules with diverse molecular weights and optical properties. The regioselective polycondensation was examined by 1H NMR spectroscopy of selected polymers. In the case of 5-membered cyclic acetal units, mixtures of the endo-H and exo-H dioxolan-2-yl system, diastereomers were formed in the polymer chain. The macrocycles and linear oligomers were identified by NMR and electrospray mass spectrometry (ESI-MS). Thermodynamically controlled reactions for making macrocycles as well as oligomers in the absence of templates are also discussed.

Aldehydes↗