当前位置： SCI文献检索 > BIOORGANIC & MEDICINAL CHEMISTRY期刊下所有文献 > Tailoring structure-function and targeting properties of ceramides by site-specific cationization.

Tailoring structure-function and targeting properties of ceramides by site-specific cationization.

Abstract：

:In the course of our studies on compartment-specific lipid-mediated cell regulation, we identified an intimate connection between ceramides (Cers) and the mitochondria-dependent death-signaling pathways. Here, we report on a new class of cationic Cer mimics, dubbed ceramidoids, designed to act as organelle-targeted sphingolipids (SPLs), based on conjugates of Cer and dihydroceramide (dhCer) with pyridinium salts (CCPS and dhCCPS, respectively). Ceramidoids having the pyridinium salt unit (PSU) placed internally (alpha and gamma- CCPS) or as a tether (omega-CCPS) in the N-acyl moiety were prepared by N-acylation of sphingoid bases with different omega-bromo acids or pyridine carboxylic acid chlorides following capping with respective pyridines or alkyl bromides. Consistent with their design, these analogs, showed a significantly improved solubility in water, well-resolved NMR spectra in D(2)O, broadly modified hydrophobicity, fast cellular uptake, and higher anticancer activities in cells in comparison to uncharged counterparts. Structure-activity relationship (SAR) studies in MCF-7 breast carcinoma cells revealed that the location of the PSU and its overall chain length affected markedly the cytotoxic effects of these ceramidoids. All omega-CCPSs were more potent (IC(50/48 h): 0.6-8.0 microM) than their alpha/gamma-CCPS (IC(50/48 h): 8-20 microM) or D-erythro-C6-Cer (IC(50/48 h): 15 microM) analogs. omega-DhCCPSs were also moderately potent (IC(50/48 h): 2.5-12.5 microM). Long-chain omega-dhCCPSs were rapidly and efficiently oxidized in cells to the corresponding omega-CCPSs, as established by LC-MS analysis. CCPS analogs also induced acute changes in the levels and composition of endogenous Cers (upregulation of C16-, C14-, and C18-Cers, and downregulation of C24:0- and C24:1-Cers). These novel ceramidoids illustrate the feasibility of compartment-targeted lipids, and they should be useful in cell-based studies as well as potential novel therapeutics.

journal_name

Bioorg Med Chem

journal_title

Bioorganic & medicinal chemistry

authors

Szulc ZM,Bielawski J,Gracz H,Gustilo M,Mayroo N,Hannun YA,Obeid LM,Bielawska A

doi

10.1016/j.bmc.2006.07.016

subject

Has Abstract

pub_date

2006-11-01 00:00:00

pages

7083-104

issue

21

eissn

0968-0896

issn

1464-3391

pii

S0968-0896(06)00548-7

journal_volume

14

pub_type

杂志文章

相关文献

BIOORGANIC & MEDICINAL CHEMISTRY文献大全
  • 8-Azapurines as new inhibitors of cyclin-dependent kinases.

    abstract：:Purine inhibitors of cyclin-dependent kinases (CDK) seem to be a potential anticancer drug candidate as one of the first representatives, roscovitine, is passing Phase II clinical trials for cancer and glomerulonephritis. In this article, we describe a novel modification of the purine scaffold influencing CDK2 inhibit...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2005.06.007

    authors： Havlicek L,Fuksova K,Krystof V,Orsag M,Vojtesek B,Strnad M

    更新日期：2005-09-15 00:00:00

  • Synthesis and biological evaluation of largazole zinc-binding group analogs.

    abstract：:Histone acetylation is an extensively investigated post-translational modification that plays an important role as an epigenetic regulator. It is controlled by histone acetyl transferases (HATs) and histone deacetylases (HDACs). The overexpression of HDACs and consequent hypoacetylation of histones have been observed ...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2017.03.071

    authors： Kim B,Ratnayake R,Lee H,Shi G,Zeller SL,Li C,Luesch H,Hong J

    更新日期：2017-06-15 00:00:00

  • 2-Methylene 19-nor-25-dehydro-1alpha-hydroxyvitamin D3 26,23-lactones: synthesis, biological activities and molecular basis of passive antagonism.

    abstract：:To investigate the molecular mechanism of vitamin D receptor (VDR) antagonists having no structurally bulky group interfering with helix 12 of the ligand-binding domain of the VDR, we have synthesized four diastereomers at C(20) and C(23) of 19-nor-1alpha-hydroxyvitamin D(3) 25-methylene-26,23-lactone bearing a 2MD-ty...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2007.09.017

    authors： Yoshimoto N,Inaba Y,Yamada S,Makishima M,Shimizu M,Yamamoto K

    更新日期：2008-01-01 00:00:00

  • Carbonic anhydrase inhibitors: Design, synthesis, kinetic, docking and molecular dynamics analysis of novel glycine and phenylalanine sulfonamide derivatives.

    abstract：:The inhibition of two human cytosolic carbonic anhydrase isozymes I and II, with some novel glycine and phenylalanine sulfonamide derivatives were investigated. Newly synthesized compounds G1-4 and P1-4 showed effective inhibition profiles with KI values in the range of 14.66-315μM for hCA I and of 18.31-143.8μM again...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2015.10.009

    authors： Fidan İ,Salmas RE,Arslan M,Şentürk M,Durdagi S,Ekinci D,Şentürk E,Coşgun S,Supuran CT

    更新日期：2015-12-01 00:00:00

  • Synthesis and antidepressant-like action of stereoisomers of imidobenzenesulfonylaziridines in mice evaluated in the forced swimming test.

    abstract：:The present study describes the chemical synthesis and pharmacological evaluation of a new series of eleven compounds stereoisomers of imidobenzenesulfonylaziridines in the forced-swimming test (FST) in mice. The pharmacological results of these compounds show that six of them, given intraperitoneally, reduced the imm...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2006.03.036

    authors： Duarte FS,Andrade Eda S,Vieira RA,Uieara M,Nunes RJ,de Lima TC

    更新日期：2006-08-01 00:00:00

  • Synthesis and Pin1 inhibitory activity of thiazole derivatives.

    abstract：:Pin1 (Protein interacting with NIMA1) is a peptidyl prolyl cis-trans isomerase (PPIase) which specifically catalyze the conformational conversion of the amide bond of pSer/Thr-Pro motifs in its substrate proteins and is a novel promising anticancer target. A series of new thiazole derivatives were designed and synthes...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2016.09.049

    authors： Zhao H,Cui G,Jin J,Chen X,Xu B

    更新日期：2016-11-15 00:00:00

  • Synthesis, nicotinic acetylcholine receptor binding, antinociceptive and seizure properties of methyllycaconitine analogs.

    abstract：:A series of methyllycaconitine (1a, MLA) analogs was synthesized where the (S)-2-methylsuccinimidobenzoyl group in MLA was replaced with a (R)-2-methyl, 2,2-dimethyl-, 2,3-dimethyl, 2-phenyl-, and 2-cyclohexylsuccinimidobenzoyl (1b-f) group. The analogs 1b-f were evaluated for their inhibition of [(125)I]iodo-MLA bind...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2006.10.061

    authors： Ivy Carroll F,Ma W,Navarro HA,Abraham P,Wolckenhauer SA,Damaj MI,Martin BR

    更新日期：2007-01-15 00:00:00

  • Modeling and synthesis of novel tight-binding inhibitors of cytochrome P450 2C9.

    abstract：:Cytochrome P450 2C9 (2C9) is one of the three major drug metabolizing cytochrome P450 enzymes in human liver. Although the crystal structure of 2C9 has been solved, the important physicochemical properties of substrate-enzyme interactions remain difficult to be determined. This is due in part to the conformational fle...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2008.01.021

    authors： Peng CC,Rushmore T,Crouch GJ,Jones JP

    更新日期：2008-04-01 00:00:00

  • (S)-Erypoegin K, an isoflavone isolated from Erythrina poeppigiana, is a novel inhibitor of topoisomerase IIα: Induction of G2 phase arrest in human gastric cancer cells.

    abstract：:Erypoegin K, an isoflavone isolated from the stem bark of Erythrina poeppigiana, has a single chiral carbon in its structure and exists naturally as a racemic mixture. Our previous study showed (S)-erypoegin K selectively exhibits potent anti-proliferative and apoptosis-inducing activity against human leukemia HL-60 c...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2020.115904

    authors： Hikita K,Yamakage Y,Okunaga H,Motoyama Y,Matsuyama H,Matsuoka K,Murata T,Nakayoshi T,Oda A,Kato K,Tanaka H,Asao N,Dan S,Kaneda N

    更新日期：2021-01-15 00:00:00

  • Synthesis and evaluation of verticipyrone analogues as mitochondrial complex I inhibitors.

    abstract：:Verticipyrone has recently been isolated from the culture broth of Verticillium sp. and shown to inhibit NADH fumarate reductase, as well as NADH oxidoreductase (complex I) of the mitochondrial electron transport chain. In order to assess the structural elements in verticipyrone essential for complex I inhibitor, 15 s...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2010.03.070

    authors： Leiris SJ,Khdour OM,Segerman ZJ,Tsosie KS,Chapuis JC,Hecht SM

    更新日期：2010-05-15 00:00:00

  • Synthesis and binding affinities of fluoroalkylated raloxifenes.

    abstract：:Three fluoroalkylated derivatives (1-3) of the selective estrogen receptor modulator (SERM), raloxifene, have been synthesized. The key step in the synthesis is the C-C bond formation of benzo[b]thiophene and a substituted phenyl group (ring C) using a Stille reaction. The in vitro binding affinities of the substitute...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/s0968-0896(03)00362-6

    authors： Lee KC,Moon BS,Lee JH,Chung KH,Katzenellenbogen JA,Chi DY

    更新日期：2003-08-15 00:00:00

  • Relationship between structure and permeability of dipeptide derivatives containing tryptophan and related compounds across human intestinal epithelial (Caco-2) cells.

    abstract：:The permeability of dipeptide derivatives containing tryptophans and indole derivatives through Caco-2 cells was used as an in vitro intestinal absorption model in order to clarify structural factors which influence their intestinal epithelial permeation and metabolism. Most peptide derivatives were hydrolysed not onl...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2003.10.001

    authors： Ano R,Kimura Y,Urakami M,Shima M,Matsuno R,Ueno T,Akamatsu M

    更新日期：2004-01-02 00:00:00

  • Discovery, synthesis and biological evaluation of isoquinolones as novel and highly selective JNK inhibitors (2).

    abstract：:3-Metoxycarbonyl isoquinolone derivative 1 has been identified as a potent JNK inhibitor and significantly inhibited cardiac hypertrophy in a rat pressure-overload model. Herein, a series of isoquinolones with an imidazolylmethyl or a pyrazolylmethyl group at the 2-position were designed based on X-ray crystallographi...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2008.02.028

    authors： Asano Y,Kitamura S,Ohra T,Itoh F,Kajino M,Tamura T,Kaneko M,Ikeda S,Igata H,Kawamoto T,Sogabe S,Matsumoto S,Tanaka T,Yamaguchi M,Kimura H,Fukumoto S

    更新日期：2008-04-15 00:00:00

  • Comparative molecular field analysis of colchicine inhibition and tubulin polymerization for combretastatins binding to the colchicine binding site on beta-tubulin.

    abstract：:A molecular modeling study using Comparative Molecular Field Analysis (CoMFA) was undertaken to develop a predictive model for combretastatin binding to the colchicine binding site of tubulin. Furthermore, we examined the potential contribution of lipophilicity (log P) and molecular dipole moment and were unable to co...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/s0968-0896(00)00068-7

    authors： Brown ML,Rieger JM,Macdonald TL

    更新日期：2000-06-01 00:00:00

  • Structure-based design and discovery of novel inhibitors of protein tyrosine phosphatases.

    abstract：:Protein tyrosine phosphatases (PTPs) are important in the regulation of signal transduction processes. Certain enzymes of this class are considered as potential therapeutic targets in the treatment of a variety of diseases such as diabetes, inflammation, and cancer. However, many PTP inhibitors identified to date are ...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/s0968-0896(03)00039-7

    authors： Huang P,Ramphal J,Wei J,Liang C,Jallal B,McMahon G,Tang C

    更新日期：2003-04-17 00:00:00

  • Synthesis, antiproliferative and pro-apoptotic activity of 2-phenylindoles.

    abstract：:Breast cancer is the second most common cancer worldwide after lung cancer with the vast majority of early stage breast cancers being hormone-dependent. One of the major therapeutic advances in the clinical treatment of breast cancer has been the introduction of selective estrogen receptor modulators (SERMs). We descr...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2016.06.050

    authors： Kelly PM,Bright SA,Fayne D,Pollock JK,Zisterer DM,Williams DC,Meegan MJ

    更新日期：2016-09-15 00:00:00

  • Chemical and enzymatic synthesis of fructose analogues as probes for import studies by the hexose transporter in parasites.

    abstract：:Various D-fructose analogues modified at C-1 or C-6 positions were synthesized from D-glucose by taking advantage of the Amadori rearrangement or using the aldol condensation between dihydroxyacetone phosphate and appropriate aldehyde catalyzed by fructose 1,6-diphosphate aldolase from rabbit muscle. The affinities of...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/s0968-0896(00)00018-3

    authors： Azéma L,Bringaud F,Blonski C,Périé J

    更新日期：2000-04-01 00:00:00

  • Click approach to the discovery of 1,2,3-triazolylsalicylamides as potent Aurora kinase inhibitors.

    abstract：:A series of 1,2,3-triazolylsalicylamide derivatives has been developed from the antiproliferative agent 7 and was evaluated for their Aurora kinase inhibitory activity. The novel 1,2,3-triazolylsalicylamide scaffold could be readily assembled by Cu(I)-catalyzed azide-alkyne 1,3-dipolar cycloaddition, allowing rapid ac...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2014.06.047

    authors： Song D,Park Y,Yoon J,Aman W,Hah JM,Ryu JS

    更新日期：2014-09-01 00:00:00

  • Study on dual-site inhibitors of acetylcholinesterase: Highly potent derivatives of bis- and bifunctional huperzine B.

    abstract：:Natural (-)-huperzine B (HupB), isolated from Chinese medicinal herb, displayed moderate inhibitory activity of acetylcholinesterase (AChE). Based on the active dual-site of AChE, a series of novel derivatives of bis- and bifunctional HupB were designed and synthesized. The AChE inhibition potency of most derivatives ...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2006.11.009

    authors： He XC,Feng S,Wang ZF,Shi Y,Zheng S,Xia Y,Jiang H,Tang XC,Bai D

    更新日期：2007-02-01 00:00:00

  • Synthesis and binding affinities of methylvesamicol analogs for the acetylcholine transporter and sigma receptor.

    abstract：:We synthesized methylvesamicol analogs 13-16 and investigated the binding characteristics of 2-[4-phenylpiperidino]cyclohexanol (vesamicol) and methylvesamicol analogs 13-16, with a methyl group introduced into the 4-phenylpiperidine moiety, to sigma receptors (sigma-1, sigma-2) and to vesicular acetylcholine transpor...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2005.11.044

    authors： Shiba K,Ogawa K,Ishiwata K,Yajima K,Mori H

    更新日期：2006-04-15 00:00:00

  • Differential receptor binding characteristics of consecutive phenylalanines in micro-opioid specific peptide ligand endomorphin-2.

    abstract：:Endogenous opioid peptides consist of a conserved amino acid residue of Phe(3) and Phe(4), although their binding modes for opioid receptors have not been elucidated in detail. Endomorphin-2, which is highly selective and specific for the mu opioid receptor, possesses two Phe residues at the consecutive positions 3 an...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2007.03.009

    authors： Honda T,Shirasu N,Isozaki K,Kawano M,Shigehiro D,Chuman Y,Fujita T,Nose T,Shimohigashi Y

    更新日期：2007-06-01 00:00:00

  • Cyclopentitol as a scaffold for a natural product-like compound library for drug discovery.

    abstract：:A concise and efficient synthesis of cyclopentitols as a scaffold for a two-dimensional compound library for drug discovery is described. Starting from d-mannose, the key steps are Wittig olefination and ring-closing metathesis (RCM) followed by a [3,3]-sigmatropic Overmann rearrangement to form an sp(3)-rich, natural...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2015.01.040

    authors： Padwal JD,Filippov DV,Narhe BD,Aertssen S,Beuving RJ,Benningshof JC,van der Marel GA,Overkleeft HS,van der Stelt M

    更新日期：2015-06-01 00:00:00

  • BRACO19 analog dimers with improved inhibition of telomerase and hPot 1.

    abstract：:Human chromosomes terminate with telomeres, which contain double-stranded G-rich, repetitive DNA followed by a single-stranded overhang of the G-rich sequence. Single-stranded oligonucleotides containing G-rich telomeric repeats have been observed in vitro to fold into a variety of G-quadruplex topologies depending on...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2009.01.015

    authors： Fu YT,Keppler BR,Soares J,Jarstfer MB

    更新日期：2009-03-01 00:00:00

  • Synthesis, electronic properties, antioxidant and antibacterial activity of some new benzimidazoles.

    abstract：:Two groups of benzimidazole derivatives were synthesized using as precursors 5(6)-substituted 2-mercapto-benzimidazol-thiols and their antioxidant activity was investigated using TBA-MDA test. In the group of 1,3-disubstituted-benzimidazol-2-imines the highest lipid peroxidation inhibition effect 74.04% (IC₅₀=141.89 μ...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2015.08.029

    authors： Mavrova ATs,Yancheva D,Anastassova N,Anichina K,Zvezdanovic J,Djordjevic A,Markovic D,Smelcerovic A

    更新日期：2015-10-01 00:00:00

  • Synthesis and cytotoxic activities of goniothalamins and derivatives.

    abstract：:Substituted goniothalamins containing cyclopropane-groups were efficiently prepared in high yields and good selectivity. Antiproliferative activity was measured on three human cancer cell lines (A549, MCF-7, HBL-100), to show which of the structural elements of goniothalamins is mandatory for cytotoxicity. We found th...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2017.02.004

    authors： Weber A,Döhl K,Sachs J,Nordschild ACM,Schröder D,Kulik A,Fischer T,Schmitt L,Teusch N,Pietruszka J

    更新日期：2017-11-15 00:00:00

  • Characterization and in vitro activity of a branched peptide boronic acid that interacts with HIV-1 RRE RNA.

    abstract：:A branched peptide containing multiple boronic acids was found to bind RRE IIB selectively and inhibit HIV-1 p24 capsid production in a dose-dependent manner. Structure-activity relationship studies revealed that branching in the peptide is crucial for the low micromolar binding towards RRE IIB, and the peptide demons...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2016.04.009

    authors： Wynn JE,Zhang W,Tebit DM,Gray LR,Hammarskjold ML,Rekosh D,Santos WL

    更新日期：2016-09-01 00:00:00

  • A new opioid designed multiple ligand derived from the micro opioid agonist endomorphin-2 and the delta opioid antagonist pharmacophore Dmt-Tic.

    abstract：:Opioid compounds with mixed micro agonist/delta antagonist properties could be used as analgesics with low propensity to induce tolerance and dependence. Here we report the synthesis of a new designed multiple ligand deriving from the micro selective agonist endomorphin-2 and the delta selective antagonist pharmacopho...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2007.08.047

    authors： Salvadori S,Trapella C,Fiorini S,Negri L,Lattanzi R,Bryant SD,Jinsmaa Y,Lazarus LH,Balboni G

    更新日期：2007-11-15 00:00:00

  • Lead identification and optimization of bacterial glutamate racemase inhibitors.

    abstract：:Mycobacterium tuberculosis glutamate racemase is an essential enzyme involved in peptidoglycan synthesis and conserved in most bacteria. Small molecule inhibitors were reported on other bacterial species whereas in M. tuberculosis it wasn't explored much. In this study we have screened in house compound library using ...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2017.11.031

    authors： Malapati P,Siva Krishna V,Nallangi R,Meda N,Reshma Srilakshmi R,Sriram D

    更新日期：2018-01-01 00:00:00

  • Aromatic radiofluorination and biological evaluation of 2-aryl-6-[18F]fluorobenzothiazoles as a potential positron emission tomography imaging probe for β-amyloid plaques.

    abstract：:To develop agents for radionuclide imaging Aβ plaques in vivo, we prepared three fluorine-substituted analogs of arylbenzothiazole class; compound 2 has a high affinity for Aβ (K(i)=5.5nM) and the specific binding to Aβ in fluorescent staining. In preparation for the synthesis of these arylbenzothiazole analogs in rad...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2011.03.029

    authors： Lee BC,Kim JS,Kim BS,Son JY,Hong SK,Park HS,Moon BS,Jung JH,Jeong JM,Kim SE

    更新日期：2011-05-01 00:00:00

  • Protease inhibitors. Part 8: synthesis of potent Clostridium histolyticum collagenase inhibitors incorporating sulfonylated L-alanine hydroxamate moieties.

    abstract：:A series of hydroxamates was prepared by reaction of alkyl/arylsulfonyl halides with N-2-chlorobenzyl-L-alanine, followed by conversion of the COOH moiety to the CONHOH group, with hydroxylamine in the presence of carbodiimides. Other structurally related compounds were obtained by reaction of N-2-chlorobenzyl-L-alani...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/s0968-0896(99)00316-8

    authors： Scozzafava A,Supuran CT

    更新日期：2000-03-01 00:00:00