当前位置： SCI文献检索 > BIOORGANIC & MEDICINAL CHEMISTRY LETTERS期刊下所有文献 > Structure-activity and in vivo evaluation of a novel lipoprotein lipase (LPL) activator.

Structure-activity and in vivo evaluation of a novel lipoprotein lipase (LPL) activator.

Abstract：

:Elevated triglycerides (TG) contribute towards increased risk for cardiovascular disease. Lipoprotein lipase (LPL) is an enzyme that is responsible for the metabolism of core triglycerides of very-low density lipoproteins (VLDL) and chylomicrons in the vasculature. In this study, we explored the structure-activity relationships of our lead compound (C10d) that we have previously identified as an LPL agonist. We found that the cyclopropyl moiety of C10d is not absolutely necessary for LPL activity. Several substitutions were found to result in loss of LPL activity. The compound C10d was also tested in vivo for its lipid lowering activity. Mice were fed a high-fat diet (HFD) for four months, and treated for one week at 10mg/kg. At this dose, C10d exhibited in vivo biological activity as indicated by lower TG and cholesterol levels as well as reduced body fat content as determined by ECHO-MRI. Furthermore, C10d also reduced the HFD induced fat accumulation in the liver. Our study has provided insights into the structural and functional characteristics of this novel LPL activator.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Geldenhuys WJ,Caporoso J,Leeper TC,Lee YK,Lin L,Darvesh AS,Sadana P

doi

10.1016/j.bmcl.2016.11.053

subject

Has Abstract

pub_date

2017-01-15 00:00:00

pages

303-308

issue

2

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(16)31204-5

journal_volume

27

pub_type

杂志文章

相关文献

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS文献大全
  • Marine sponge alkaloids as a source of anti-bacterial adjuvants.

    abstract：:Novel approaches that do not rely upon developing microbicidal compounds are sorely needed to combat multidrug resistant (MDR) bacteria. The potential of marine secondary metabolites to serve as a source of non-traditional anti-bacterial agents is demonstrated by showing that pyrrole-imidazole alkaloids inhibit biofil...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2016.11.018

    authors： Melander RJ,Liu HB,Stephens MD,Bewley CA,Melander C

    更新日期：2016-12-15 00:00:00

  • Differential activity of rosiglitazone enantiomers at PPAR gamma.

    abstract：:Analysis of the enantiomers of rosiglitazone in a PPAR gamma binding assay suggests that the (S)-(-)-isomer is responsible for the antidiabetic activity. ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(98)00664-7

    authors： Parks DJ,Tomkinson NC,Villeneuve MS,Blanchard SG,Willson TM

    更新日期：1998-12-15 00:00:00

  • Sodium channel activity and sigma binding of 2-aminopropanamide anticonvulsants.

    abstract：:Sodium channel blocking, anticonvulsant activity, and sigma (sigma) binding of selected leads in a series of alpha-amino amide anticonvulsants were examined. While anticonvulsant compounds were always endowed with low micromolar sodium (Na+) channel site-2 binding, compounds with low site-2 Na+ channel affinity failed...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(99)00415-1

    authors： Pevarello P,Bonsignori A,Caccia C,Amici R,McArthur RA,Fariello RG,Salvati P,Varasi M

    更新日期：1999-09-06 00:00:00

  • A divergent chemoenzymatic route to an intermediate for nucleoside analogues.

    abstract：:Two regioisomeric isoxazoline monoacetates 1 and 2 were synthesized from the corresponding diacetate 3 via PPL or PLE catalyzed hydrolysis. With both the enzymes, the initial regioselectivity (approximately 3-4:1) was offset by an intramolecular acyl transfer. In addition to a non-enzymatic catalysis for the acyl tran...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2005.03.033

    authors： Basak A,Bisai S

    更新日期：2005-05-16 00:00:00

  • Towards new antibiotics targeting bacterial transglycosylase: Synthesis of a Lipid II analog as stable transition-state mimic inhibitor.

    abstract：:Described here is the asymmetric synthesis of iminosugar 2b, a Lipid II analog, designed to mimic the transition state of transglycosylation catalyzed by the bacterial transglycosylase. The high density of functional groups, together with a rich stereochemistry, represents an extraordinary challenge for chemical synth...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2018.03.035

    authors： Wang X,Krasnova L,Wu KB,Wu WS,Cheng TJ,Wong CH

    更新日期：2018-09-01 00:00:00

  • PSMA-targeted bispecific Fab conjugates that engage T cells.

    abstract：:Bioconjugate formats provide alternative strategies for antigen targeting with bispecific antibodies. Here, PSMA-targeted Fab conjugates were generated using different bispecific formats. Interchain disulfide bridging of an αCD3 Fab enabled installation of either the PSMA-targeting small molecule DUPA (SynFab) or the ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2017.09.065

    authors： Patterson JT,Isaacson J,Kerwin L,Atassi G,Duggal R,Bresson D,Zhu T,Zhou H,Fu Y,Kaufmann GF

    更新日期：2017-12-15 00:00:00

  • Identification of novel BRAF kinase inhibitors with structure-based virtual screening.

    abstract：:VRAF murine sarcoma viral oncogene homologue B1 (BRAF) kinase has proved to be a promising target for the development of therapeutics for the treatment of a variety of human cancers. Here, we report the first example of a successful application of the structure-based virtual screening to identify novel BRAF inhibitors...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2011.08.010

    authors： Park H,Choi H,Hong S,Hong S

    更新日期：2011-10-01 00:00:00

  • Transformation of quercitols into 4-methylenecyclohex-5-ene-1,2,3-triol derivatives, precursors for the chemical chaperones N-octyl-4-epi-β-valienamine (NOEV) and N-octyl-β-valienamine (NOV).

    abstract：:(+)-proto-Quercitol (1) and (-)-vibo-quercitol (2), both of which could be readily prepared by the bioconversion of myo-inositol, were successfully converted into the corresponding 4-methylenecyclohex-5-ene-1,2,3-triol derivatives. These compounds were demonstrated to be suitable precursors, preserving their configura...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2011.09.067

    authors： Kuno S,Takahashi A,Ogawa S

    更新日期：2011-12-01 00:00:00

  • Combinatorial synthesis of SSAO inhibitors using sonogashira coupling: SAR of aryl propargylic amines.

    abstract：:The structure-activity relationships for semicarbazide-sensitive amine oxidase (SSAO) inhibitors based on arylpropynylamines was investigated using solution-phase combinatorial Sonogashira coupling. The results suggest that binding to the active site occurs by coordination of the amine to the proximal copper(II) and f...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(01)00506-6

    authors： Conn C,Shimmon R,Cordaro F,Hargraves TL,Ibrahim P

    更新日期：2001-10-08 00:00:00

  • Anti-tubercular agents. Part IV: Synthesis and antimycobacterial evaluation of nitroheterocyclic-based 1,2,4-benzothiadiazines.

    abstract：:In continuation of our earlier work on benzothiadiazines, we have prepared a series of nitrofuran, nitrothiophene and arylfuran coupled benzothiadiazines and evaluated them for antimycobacterial and antibacterial activities. One of the compounds 2f has shown good in vitro antimycobacterial activity. All the synthesize...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2007.07.027

    authors： Kamal A,Ahmed SK,Reddy KS,Khan MN,Shetty RV,Siddhardha B,Murthy US,Khan IA,Kumar M,Sharma S,Ram AB

    更新日期：2007-10-01 00:00:00

  • Inhibitory effects of polyphenols toward HCV from the mangrove plant Excoecaria agallocha L.

    abstract：:Four new polyphenols namely excoecariphenols A-D (1-4) were isolated from the Chinese mangrove plant Excoecaria agallocha L. together with 23 known phenolic compounds. The structures of new compounds were elucidated on the basis of extensive spectroscopic analyses including IR, MS, NMR, and CD data. Excoecariphenols A...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2011.11.109

    authors： Li Y,Yu S,Liu D,Proksch P,Lin W

    更新日期：2012-01-15 00:00:00

  • Synthesis and evaluation of N-[(1S,2S)-3-(4-chlorophenyl)-2-(3-cyanophenyl)-1-methylpropyl]-2-methyl-2-aminopropanamide as human cannabinoid-1 receptor (CB1R) inverse agonists.

    abstract：:Obesity is a chronic medical condition that is affecting large population throughout the world. CB1 as a target for treatment of obesity has been under intensive studies. Taranabant was discovered and then developed by Merck as the 1st generation CB1R inverse agonist. Reported here is part of our effort on the 2nd gen...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2009.07.046

    authors： Du W,Jewell JP,Lin LS,Colandrea VJ,Xiao JC,Lao J,Shen CP,Bateman TJ,Reddy VB,Ha SN,Shah SK,Fong TM,Hale JJ,Hagmann WK

    更新日期：2009-09-01 00:00:00

  • Synthesis and antituberculosis activity of novel mefloquine-isoxazole carboxylic esters as prodrugs.

    abstract：:5-(2,8-Bis(trifluoromethyl)quinolin-4-yloxymethyl)isoxazole-3-carboxylic acid ethyl ester (compound 3) was reported to have excellent antituberculosis activity against both replicating and non-replicating Mycobacterium tuberculosis, with a minimum inhibitory concentration (MIC) of 0.9 microM and 12.2 microM, respectiv...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2009.11.105

    authors： Mao J,Yuan H,Wang Y,Wan B,Pak D,He R,Franzblau SG

    更新日期：2010-02-01 00:00:00

  • Anion inhibition studies of a β-carbonic anhydrase from Clostridium perfringens.

    abstract：:A β-carbonic anhydrases (CAs, EC 4.2.1.1) was recently cloned, purified and characterized kinetically in the pathogen Clostridium perfringens. We report here the first inhibition study of this enzyme (CpeCA). CpeCA was poorly inhibited by iodide and bromide, and was inhibited with KIs in the range of 1-10mM by a range...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2013.10.037

    authors： Vullo D,Sai Kumar RS,Scozzafava A,Capasso C,Ferry JG,Supuran CT

    更新日期：2013-12-15 00:00:00

  • Kinesin spindle protein (KSP) inhibitors. Part V: discovery of 2-propylamino-2,4-diaryl-2,5-dihydropyrroles as potent, water-soluble KSP inhibitors, and modulation of their basicity by beta-fluorination to overcome cellular efflux by P-glycoprotein.

    abstract：:Installation of a C2-aminopropyl side chain to the 2,4-diaryl-2,5-dihydropyrrole series of kinesin spindle protein (KSP) inhibitors results in potent, water soluble compounds, but the aminopropyl group induces susceptibility to cellular efflux by P-glycoprotein (Pgp). We show that by carefully modulating the basicity ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2007.03.006

    authors： Cox CD,Breslin MJ,Whitman DB,Coleman PJ,Garbaccio RM,Fraley ME,Zrada MM,Buser CA,Walsh ES,Hamilton K,Lobell RB,Tao W,Abrams MT,South VJ,Huber HE,Kohl NE,Hartman GD

    更新日期：2007-05-15 00:00:00

  • Discovery and biological evaluation of adamantyl amide 11beta-HSD1 inhibitors.

    abstract：:A series of adamantyl amide 11beta-HSD1 inhibitors has been discovered and chemically modified. Selected compounds are selective for 11beta-HSD1 over 11beta-HSD2 and possess excellent cellular potency in human and murine 11beta-HSD1 assays. Good pharmacodynamic characteristics are observed in ex vivo assays. ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2007.02.057

    authors： Webster SP,Ward P,Binnie M,Craigie E,McConnell KM,Sooy K,Vinter A,Seckl JR,Walker BR

    更新日期：2007-05-15 00:00:00

  • Identification of a glutathione peroxidase inhibitor that reverses resistance to anticancer drugs in human B-cell lymphoma cell lines.

    abstract：:Cancer cells isolated from two patients with malignant non-Hodgkin B-cell lymphomas that became resistant to chemotherapy during clinical treatment were made ≥fourfold resistant in culture to anticancer drugs, that is cisplatin, etoposide, methotrexate and bortezomib. Because most resistant lines showed significantly ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2012.08.091

    authors： Schulz R,Emmrich T,Lemmerhirt H,Leffler U,Sydow K,Hirt C,Kiefer T,Link A,Bednarski PJ

    更新日期：2012-11-01 00:00:00

  • Synthesis and anti-proliferative activity of aromatic substituted 5-((1-benzyl-1H-indol-3-yl)methylene)-1,3-dimethylpyrimidine-2,4,6(1H,3H,5H)-trione analogs against human tumor cell lines.

    abstract：:Based on previous SAR studies on N-benzylindole and barbituric acid hybrid molecules, we have synthesized a series of aromatic substituted 5-((1-benzyl-1H-indol-3-yl)methylene)-1,3-dimethylpyrimidine-2,4,6(1H,3H,5H)-trione analogs (3a-i) and evaluated them for their in vitro growth inhibition and cytotoxicity against ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2013.12.013

    authors： Madadi NR,Penthala NR,Janganati V,Crooks PA

    更新日期：2014-01-15 00:00:00

  • Synthesis and anti-influenza virus activity of 7-O-alkylated derivatives related to zanamivir.

    abstract：:A series of 7-alkyl ether derivatives related to zanamivir were synthesized using direct alkylation of the C-7 alcohol of sialic acid. Alkyl ether moiety of less than 12 carbons in length showed low nanomolar inhibitory activity against influenza A virus sialidase. Furthermore, their moiety improved influenza A virus ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(02)00329-3

    authors： Honda T,Masuda T,Yoshida S,Arai M,Kaneko S,Yamashita M

    更新日期：2002-08-05 00:00:00

  • Carbonic anhydrase inhibitors: inhibition of the β-class enzyme from the pathogenic yeast Candida glabrata with sulfonamides, sulfamates and sulfamides.

    abstract：:The fungal pathogen Candida glabrata encodes for a β-carbonic anhydrase (CA, EC 4.2.1.1), CgNce103, recently discovered. Only anions have been investigated as CgNce103 inhibitors up until now. Here we report the first sulfonamides inhibition study of this enzyme. Simple sulfonamides showed weak or moderate CgNce103 in...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2013.02.092

    authors： Vullo D,Leewattanapasuk W,Mühlschlegel FA,Mastrolorenzo A,Capasso C,Supuran CT

    更新日期：2013-05-01 00:00:00

  • Multidrug resistance-reversal effects of resin glycosides from Dichondra repens.

    abstract：:Investigation of hydrophobic extract of Dichondra repens (Convolvulaceae) led to the isolation of three new resin glycosides dichondrins A-C (1-3), and three known resin glycosides cus-1, cus-2, and cuse 3. All the isolated resin glycosides with an acyclic core were evaluated for their multidrug resistance reversal ac...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2014.12.083

    authors： Song WB,Wang WQ,Zhang SW,Xuan LJ

    更新日期：2015-02-15 00:00:00

  • Optimization of arylindenopyrimidines as potent adenosine A(2A)/A(1) antagonists.

    abstract：:Two reactive metabolites were identified in vivo for the dual A(2A)/A(1) receptor antagonist 1. Two strategies were implemented to successfully mitigate the metabolic liabilities associated with 1. Optimization of the arylindenopyrimidines led to a number of amide, ether, and amino analogs having comparable in vitro a...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2010.03.024

    authors： Shook BC,Rassnick S,Chakravarty D,Wallace N,Ault M,Crooke J,Barbay JK,Wang A,Leonard K,Powell MT,Alford V,Hall D,Rupert KC,Heintzelman GR,Hansen K,Bullington JL,Scannevin RH,Carroll K,Lampron L,Westover L,Russell

    更新日期：2010-05-01 00:00:00

  • Novel targeting strategy based on multimeric ligands for drug delivery and molecular imaging: homooligomers of alpha-MSH.

    abstract：:Homooligomers constructed with 4- and 6-amino acid fragments of melanocortin (alpha-MSH) bind with higher affinity and with apparent cooperativity to melanocortin receptor, compared to their constituent monomers. Individual ligands were tethered with various spacers of different length and rigidity and the influence o...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2003.09.079

    authors： Vagner J,Handl HL,Gillies RJ,Hruby VJ

    更新日期：2004-01-05 00:00:00

  • Further constituents of Galianthe thalictroides (Rubiaceae) and inhibition of DNA topoisomerases I and IIα by its cytotoxic β-carboline alkaloids.

    abstract：:A new cytotoxic β-carboline alkaloid, 1-methyl-3-(2-hydroxypropan-2-yl)-2-(5-methoxy-9H-β-carbolin-1-yl)-cyclopentanol (1), was isolated from roots of Galianthe thalictroides, together with the alkaloid 1-(hydroxymethyl)-3-(2-hydroxypropan-2-yl)-2-(5-methoxy-9H-β-carbolin-1-yl)-cyclopentanol (2), the anthraquinones 1-...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2014.01.039

    authors： de Oliveira Figueiredo P,Perdomo RT,Garcez FR,de Fatima Cepa Matos M,de Carvalho JE,Garcez WS

    更新日期：2014-03-01 00:00:00

  • Yohimbine dimers exhibiting binding selectivities for human alpha2a- versus alpha2b-adrenergic receptors.

    abstract：:A series of yohimbine dimers was prepared and evaluated at the human alpha2a- and alpha2b-adrenergic receptors (ARs) expressed in Chinese hamster ovary (CHO) cells. All dimers display higher binding selectivities for alpha2a versus alpha2b subtype than yohimbine, and four compounds (3d, 3e, 3g and 3i) represent the mo...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(00)00068-8

    authors： Zheng W,Lei L,Lalchandani S,Sun G,Feller DR,Miller DD

    更新日期：2000-04-03 00:00:00

  • Interaction of heterocyclic thiols/thiones eliminated from cephalosporins with iodine and its biological implications.

    abstract：:Hydrolysis of beta-lactam antibiotics by beta-lactamases (e.g., metallo-beta-lactamase, mbetal) is one of the major bacterial defense systems. These enzymes can catalyze the hydrolysis of a variety of antibiotics including the latest generation of cephalosporins, cephamycins and imipenem. It is shown in this paper tha...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2010.04.087

    authors： Tamilselvi A,Mugesh G

    更新日期：2010-06-15 00:00:00

  • Phosphodiesterase inhibitors. Part 1: Synthesis and structure-activity relationships of pyrazolopyridine-pyridazinone PDE inhibitors developed from ibudilast.

    abstract：:Ibudilast [1-(2-isopropylpyrazolo[1,5-a]pyridin-3-yl)-2-methylpropan-1-one] is a nonselective phosphodiesterase inhibitor used clinically to treat asthma. Efforts to selectively develop the PDE3- and PDE4-inhibitory activity of ibudilast led to replacement of the isopropyl ketone by a pyridazinone heterocycle. Structu...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2011.04.021

    authors： Allcock RW,Blakli H,Jiang Z,Johnston KA,Morgan KM,Rosair GM,Iwase K,Kohno Y,Adams DR

    更新日期：2011-06-01 00:00:00

  • Kinetic delay of cyclization/elimination-coupled enzyme assays: analysis and solution.

    abstract：:A kinetic analysis of an enzyme assay employing a synthetic substrate that produces a detectable signal through a spontaneous organic cyclization/elimination reaction following the enzymatic reaction was conducted. The results from the calculation were used to predict the lag period and provide accurate measurements o...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2010.09.104

    authors： Xue F,Seto CT

    更新日期：2011-02-01 00:00:00

  • Lp-PLA2 inhibitory activities of fatty acid glycerols isolated from Saururus chinensis roots.

    abstract：:(R)-Glycerol-monolinoleate 4 and (R)-glycerol-monostearate 5 were isolated from the ethyl acetate extracts of Saururus chinensis roots and (R)- or (S)-fatty acid glycerols 4 and 5 were synthesized for confirming their structures and evaluating their inhibitory activities against Lp-PLA(2). The (R)-4 and (S)-4 exhibite...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2005.05.056

    authors： Lee WS,Kim MJ,Beck YI,Park YD,Jeong TS

    更新日期：2005-08-01 00:00:00

  • Highly increased cellular accumulation of vincristine, a useful hydrophobic antitumor-drug, in multidrug-resistant solid cancer cells induced by a simply reduced taxinine.

    abstract：:Regio- and/or chemo-selective reductions of taxinine (1a), a taxane diterpenoid readily obtainable from the needles of a Japanese yew (Taxus cuspidata), at the 5-O-cinnamoyl and 4-exo-methylene moieties have been accomplished by the catalytic hydrogenation over Pd/C or Rh/C to obtain 5-O-phenylpropionylated taxinine A...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(99)00620-4

    authors： Sako M,Suzuki H,Yamamoto N,Hirota K

    更新日期：1999-12-20 00:00:00