当前位置： SCI文献检索 > BIOORGANIC & MEDICINAL CHEMISTRY期刊下所有文献 > Discovery of a novel activator of 5-lipoxygenase from an anacardic acid derived compound collection.

Discovery of a novel activator of 5-lipoxygenase from an anacardic acid derived compound collection.

Abstract：

:Lipoxygenases (LOXs) and cyclooxygenases (COXs) metabolize poly-unsaturated fatty acids into inflammatory signaling molecules. Modulation of the activity of these enzymes may provide new approaches for therapy of inflammatory diseases. In this study, we screened novel anacardic acid derivatives as modulators of human 5-LOX and COX-2 activity. Interestingly, a novel salicylate derivative 23a was identified as a surprisingly potent activator of human 5-LOX. This compound showed both non-competitive activation towards the human 5-LOX activator adenosine triphosphate (ATP) and non-essential mixed type activation against the substrate linoleic acid, while having no effect on the conversion of the substrate arachidonic acid. The kinetic analysis demonstrated a non-essential activation of the linoleic acid conversion with a KA of 8.65 μM, αKA of 0.38μM and a β value of 1.76. It is also of interest that a comparable derivative 23d showed a mixed type inhibition for linoleic acid conversion. These observations indicate the presence of an allosteric binding site in human 5-LOX distinct from the ATP binding site. The activatory and inhibitory behavior of 23a and 23d on the conversion of linoleic compared to arachidonic acid are rationalized by docking studies, which suggest that the activator 23a stabilizes linoleic acid binding, whereas the larger inhibitor 23d blocks the enzyme active site.

journal_name

Bioorg Med Chem

journal_title

Bioorganic & medicinal chemistry

authors

Wisastra R,Kok PA,Eleftheriadis N,Baumgartner MP,Camacho CJ,Haisma HJ,Dekker FJ

doi

10.1016/j.bmc.2013.10.015

subject

Has Abstract

pub_date

2013-12-15 00:00:00

pages

7763-78

issue

24

eissn

0968-0896

issn

1464-3391

pii

S0968-0896(13)00880-8

journal_volume

21

pub_type

杂志文章

相关文献

BIOORGANIC & MEDICINAL CHEMISTRY文献大全
  • Synthesis and characterization of a small analogue of the anticancer natural product leinamycin.

    abstract：:Leinamycin (1) is a Streptomyces-derived natural product that displays nanomolar IC(50) values against human cancer cell lines. In the work described here, we report the synthesis and characterization of a small leinamycin analogue 19 that closely resembles the 'upper-right quadrant' of the natural product, consisting...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2012.10.021

    authors： Keerthi K,Rajapakse A,Sun D,Gates KS

    更新日期：2013-01-01 00:00:00

  • Selection of genomic target RNAs by iterative screening.

    abstract：:A growing number of proteins are known to exert their regulatory or biological functions via RNA binding. In some cases genetic interactions allow us to infer candidate targets for RNA directed regulation, but in many other cases identification of potential regulatory targets is problematic. We have developed an in vi...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/s0968-0896(01)00029-3

    authors： Brunel C,Ehresmann B,Ehresmann C,McKeown M

    更新日期：2001-10-01 00:00:00

  • Identification of a novel hormone sensitive lipase inhibitor with a reduced potential of reactive metabolites formation.

    abstract：:Hormone sensitive lipase (HSL) has emerged as an attractive target for the treatment of dyslipidemia. We previously reported compound 1 as a potent and orally active HSL inhibitor. Although an attractive profile was demonstrated, subsequent studies revealed that compound 1 has a bioactivation liability. The oxygen-car...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2017.02.045

    authors： Ogiyama T,Yamaguchi M,Kurikawa N,Honzumi S,Yamamoto Y,Sugiyama D,Takakusa H,Inoue SI

    更新日期：2017-04-01 00:00:00

  • Facile preparation of deuterium-labeled N-acylhomoserine lactones as internal standards for isotope dilution mass spectrometry.

    abstract：:N-Acylhomoserine lactones (AHLs) are widely conserved signal molecules that mediate quorum sensing in Gram-negative bacteria. In this study, deuterium-labeled AHLs were prepared for use as internal standards for isotope dilution mass spectrometry. Their utility in the sensitive and precise quantification of AHLs in cu...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2010.04.055

    authors： Kai K,Tani A,Hayashi H

    更新日期：2010-06-01 00:00:00

  • New highly active taxoids from 9beta-dihydrobaccatin-9,10-acetals. Part 4.

    abstract：:It was shown that a new taxane analogue 3, which exhibited both in vitro antitumor activity and in vivo efficacy by both i.v. and p.o. administration, was prone to be metabolized by human liver microsomes. We identified a major metabolite, M-1, generated by human liver microsomes as 20a, a hydroxylated compound at the...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/s0968-0896(03)00454-1

    authors： Takeda Y,Uoto K,Chiba J,Horiuchi T,Iwahana M,Atsumi R,Ono C,Terasawa H,Soga T

    更新日期：2003-10-01 00:00:00

  • Synthesis and in vivo evaluation of ¹⁸F-fluoroethyl GF120918 and XR9576 as positron emission tomography probes for assessing the function of drug efflux transporters.

    abstract：:The purpose of this study was to synthesize two new positron emission tomography (PET) probes, N-(4-(2-(1,2,3,4-tetrahydro-6,7-dimethoxy-2-isoquinolinyl)ethyl)phenyl)-9,10-dihydro-5-[¹⁸F]fluoroethoxy-9-oxo-4-acridine carboxamide ([¹⁸F]3) and quinoline-3-carboxylic acid [2-(4-{2-[7-(2-[¹⁸F]fluoroethoxy)-6-methoxy-3,4-d...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2010.12.004

    authors： Kawamura K,Yamasaki T,Konno F,Yui J,Hatori A,Yanamoto K,Wakizaka H,Ogawa M,Yoshida Y,Nengaki N,Fukumura T,Zhang MR

    更新日期：2011-01-15 00:00:00

  • Synthesis and structure-activity relationships of benzophenone-bearing diketopiperazine-type anti-microtubule agents.

    abstract：:KPU-105 (4), a potent anti-microtubule agent that contains a benzophenone was derived from the diketopiperazine-type vascular disrupting agent (VDA) plinabulin 3, which displays colchicine-like tubulin depolymerization activity. To develop derivatives with more potent anti-microtubule and cytotoxic activities, we furt...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2012.05.059

    authors： Yamazaki Y,Sumikura M,Masuda Y,Hayashi Y,Yasui H,Kiso Y,Chinen T,Usui T,Yakushiji F,Potts B,Neuteboom S,Palladino M,Lloyd GK,Hayashi Y

    更新日期：2012-07-15 00:00:00

  • Design, synthesis and pharmacological evaluation of (E)-3,4-dihydroxy styryl sulfonamides derivatives as multifunctional neuroprotective agents against oxidative and inflammatory injury.

    abstract：:A novel class of (E)-3,4-dihydroxy styryl sulfonamides and their 3,4-diacetylated derivatives as caffeic acid phenethyl ester (CAPE) analogs was designed and prepared for improving stability and solubility of the lead compound. Their neuroprotective properties were assessed by several models. The results showed that t...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2013.05.043

    authors： Ning X,Guo Y,Ma X,Zhu R,Tian C,Zhang Z,Wang X,Ma Z,Liu J

    更新日期：2013-09-01 00:00:00

  • 2-Amino-4-methyl-5-phenylethyl substituted-7-N-benzyl-pyrrolo[2,3-d]pyrimidines as novel antitumor antimitotic agents that also reverse tumor resistance.

    abstract：:Gangjee et al. recently reported a novel series of 2-amino-4-methyl-5-phenylethyl substituted-7-benzyl-pyrrolo[2,3-d]pyrimidines, some of which exhibited two digit nanomolar antitumor and antimitotic activity and were not subject to P-glycoprotein (Pgp) or multidrug resistance protein 1 (MRP1) mediated tumor resistanc...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2011.05.030

    authors： Gangjee A,Namjoshi OA,Keller SN,Smith CD

    更新日期：2011-07-15 00:00:00

  • Synthesis, 3D-QSAR, and docking studies of 1-phenyl-1H-1,2,3-triazoles as selective antagonists for beta3 over alpha1beta2gamma2 GABA receptors.

    abstract：:A series of 16 1-phenyl-1H-1,2,3-triazoles with substituents at both the 4- and 5-positions of the triazole ring were synthesized, and a total of 49 compounds, including previously reported 4- or 5-monosubstituted analogues, were examined for their ability to inhibit the specific binding of [(3)H]4'-ethynyl-4-n-propyl...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2007.05.039

    authors： Alam MS,Huang J,Ozoe F,Matsumura F,Ozoe Y

    更新日期：2007-08-01 00:00:00

  • Disulfide bridge cross-linking between protein and the RNA backbone as a tool to study RNase H1.

    abstract：:The chemical cross-linking of complexes of proteins with nucleic acids is often used in structural and mechanistic studies of these oftentimes unstable and transient complexes. To date, no method has been reported for the thiol-based conjugation of proteins with an RNA backbone, mainly because of instability of the mo...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2020.115741

    authors： Hyjek-Składanowska M,Stasińska AR,Napiórkowska-Gromadzka A,Bartłomiejczak A,Seth PP,Chmielewski MK,Nowotny M

    更新日期：2020-12-01 00:00:00

  • Effect of cholesterol on DMPC phospholipid membranes and QSAR model construction in membrane-interaction QSAR study through molecular dynamics simulation.

    abstract：:In this study, both pure DMPC and DMPC/cholesterol mixed membrane monolayer were built to compare the physical-chemical properties and dynamics properties through molecular dynamics simulation and normal-mode analysis. The results show that the addition of cholesterol decreases the area of per molecule of membrane, in...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2005.11.009

    authors： Liu J,Yang L

    更新日期：2006-04-01 00:00:00

  • Bromo-deaza-SAH: a potent and selective DOT1L inhibitor.

    abstract：:Chemical inhibition of proteins involved in chromatin-mediated signaling is an emerging strategy to control chromatin compaction with the aim to reprogram expression networks to alter disease states. Protein methyltransferases constitute one of the protein families that participate in epigenetic control of gene expres...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2013.01.049

    authors： Yu W,Smil D,Li F,Tempel W,Fedorov O,Nguyen KT,Bolshan Y,Al-Awar R,Knapp S,Arrowsmith CH,Vedadi M,Brown PJ,Schapira M

    更新日期：2013-04-01 00:00:00

  • Polymer supported synthesis of a natural product-inspired oxepane library.

    abstract：:Natural product inspired compound collections are prevalidated due to the evolutionary selection of the natural product scaffolds. Their synthesis requires the development of novel strategies amenable to formats suitable for library build-up. We describe a method for the synthesis of an oxepane library inspired by the...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2014.05.039

    authors： Basu S,Waldmann H

    更新日期：2014-08-15 00:00:00

  • Synthesis, insecticidal activities and SAR of novel phthalamides targeting calcium channel.

    abstract：:In order to find novel and environmental friendly insecticides targeting the ryanodine receptor, three series of novel phthalamides containing heptafluoroisopropyl group, low fluorine atoms group and non-fluorine group were designed and synthesized. 35 novel structures of three series were obtained. Insecticidal activ...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2014.09.052

    authors： Chen Y,Li Y,Pan L,Liu J,Wan Y,Chen W,Xiong L,Yang N,Song H,Li Z

    更新日期：2014-11-15 00:00:00

  • Evaluation of 1,2,5-thiadiazoles as modulators of M₁/M₅ muscarinic receptor subtypes.

    abstract：:Studies have demonstrated the presence of allosteric binding sites on each of the muscarinic acetylcholine receptor (mAChR) subtypes. Since most drugs targeting muscarinic receptors bind to the highly conserved orthosteric binding site, they fail to achieve appreciable subtype selectivity. Targeting non-conserved allo...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2014.01.049

    authors： Maheshwari A,Rao PS,Messer WS Jr

    更新日期：2014-03-15 00:00:00

  • Synthesis and biological evaluation of purine derivatives incorporating metal chelating ligands as HIV integrase inhibitors.

    abstract：:Because of its essential role in HIV replication and lack of human counterpart, HIV integrase is an attractive target for the development of novel anti-AIDS agents. Among the recently developed integrase inhibitors, only the alpha,gamma-diketo acid (DKA) compounds were biologically validated as potent and selective in...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2006.04.011

    authors： Li X,Vince R

    更新日期：2006-08-15 00:00:00

  • Design, synthesis and molecular docking of α,β-unsaturated cyclohexanone analogous of curcumin as potent EGFR inhibitors with antiproliferative activity.

    abstract：:A type of novel α,β-unsaturated cyclohexanone analogous, which designed based on the curcumin core structure, have been discovered as potential EGFR inhibitors. These compounds exhibit potent antiproliferative activity in two human tumor cell lines (Hep G2 and B16-F10). Among them, compounds I(3) and I(12) displayed t...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2012.11.031

    authors： Xu YY,Cao Y,Ma H,Li HQ,Ao GZ

    更新日期：2013-01-15 00:00:00

  • Synthesis and anticancer evaluation of certain indolo[2,3-b]quinoline derivatives.

    abstract：:The present report describes the synthesis and anticancer evaluation of certain 11-substituted 6H-indolo[2,3-b]quinolines and their methylated derivatives. These 6H-indolo[2,3-b]quinoline derivatives 11-13 were prepared from the commercially available 1,4-dihydroxyquinoline through alkylation, chlorination, nucleophil...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2004.09.025

    authors： Chen YL,Hung HM,Lu CM,Li KC,Tzeng CC

    更新日期：2004-12-15 00:00:00

  • Synthesis and structure-activity correlations of the cytotoxic bifunctional 1,4-diamidoanthraquinone derivatives.

    abstract：:Anthraquinone-based compounds are attractive target for the design of new anticancer drugs. We have previously described a series of 1,5- and 1,4-difunctionalized anthraquinones, which exhibit different spectra of potency, together with human telomerase evaluation. The present study details the preparation of further,...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2004.09.001

    authors： Huang HS,Chiu HF,Lee AL,Guo CL,Yuan CL

    更新日期：2004-12-01 00:00:00

  • Structure-based virtual screening for novel inhibitors of the sarco/endoplasmic reticulum calcium ATPase and their experimental evaluation.

    abstract：:A public compound library with 260,000 compounds was screened virtually by computational docking for novel inhibitors of the transmembrane enzyme sarco/endoplasmic reticulum calcium ATPase (SERCA). Docking was performed with the program GOLD in conjunction with a high resolution X-ray crystal structure of SERCA. Compo...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2008.12.010

    authors： Deye J,Elam C,Lape M,Ratliff R,Evans K,Paula S

    更新日期：2009-02-01 00:00:00

  • Novel epidithiodiketopiperazines as anti-viral zinc ejectors of the Feline Immunodeficiency Virus (FIV) nucleocapsid protein as a model for HIV infection.

    abstract：:Focused libraries of multi-substituted epidithiodiketopiperazines (ETP) were prepared and evaluated for efficacy of inhibiting the nucleocapsid protein function of the Feline Immunodeficiency Virus (FIV) as a model for HIV. This activity was compared and contrasted to observed toxicity utilising an in-vitro cell cultu...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2019.07.047

    authors： Asquith CRM,Sil BC,Laitinen T,Tizzard GJ,Coles SJ,Poso A,Hofmann-Lehmann R,Hilton ST

    更新日期：2019-09-15 00:00:00

  • Activity landscape modeling of PPAR ligands with dual-activity difference maps.

    abstract：:Activation of peroxisome proliferator-activated receptor (PPAR) subtypes offers a promising strategy for the treatment of diabetes mellitus and metabolic diseases. Selective and dual PPAR agonists have been developed and the systematic characterization of their structure-activity relationships (SAR) is of major signif...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2012.04.005

    authors： Méndez-Lucio O,Pérez-Villanueva J,Castillo R,Medina-Franco JL

    更新日期：2012-06-01 00:00:00

  • Synthesis of natural product-like polyprenylated phenols and quinones: Evaluation of their neuroprotective activities.

    abstract：:Twenty-seven natural product-like polyprenylated phenols and quinones were synthesized and their neuroprotective activity was tested using human monoamine oxidase B (MAO-B) and SH-SY5Y cells. Eight compounds inhibited MAO-B (IC50 values < 25 μM) and the inhibition mode and molecular docking of two (8c and 16c) were in...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2019.115156

    authors： Kamauchi H,Oda T,Horiuchi K,Takao K,Sugita Y

    更新日期：2020-01-01 00:00:00

  • Intestinal absorption of fluorescence-derivatized cationic peptide 001-C8-NBD via adsorptive-mediated transcytosis.

    abstract：:The intestinal absorption of an intact oligopeptide was investigated in rats using a synthetic cationic peptide, 001-C8 (H-MeTyr-Arg-MeArg-D-Leu-NH(CH2)8NH2). The peptide was coupled with 4-nitrobenzo-2-oxa-1,3-diazole (NBD) to prepare a fluorescence-labeled derivative 001-C8-NBD (H-MeTyr-Arg-MeArg-D-Leu-NH(CH2)8NH-NB...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/s0968-0896(98)00031-5

    authors： Sai Y,Kajita M,Tamai I,Kamata M,Wakama J,Wakamiya T,Tsuji A

    更新日期：1998-06-01 00:00:00

  • Fluoroalkene modification of mercaptoacetamide-based histone deacetylase inhibitors.

    abstract：:Inhibitors of histone deacetylases (HDAC) are emerging as a promising class of anti-cancer agents. The mercaptoacetoamide-based inhibitors are reported to be less toxic than hydroxamate and are worthy of further consideration. Therefore, we have designed a series of analogs as potential inhibitors of HDACs, in which t...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2009.12.005

    authors： Osada S,Sano S,Ueyama M,Chuman Y,Kodama H,Sakaguchi K

    更新日期：2010-01-15 00:00:00

  • Synthesis of novel 5-amino-thiazolo[4,5-d]pyrimidines as E. coli and S. aureus SecA inhibitors.

    abstract：:An efficient synthesis of a library of 5-amino-thiazolo[4,5-d]pyrimidines is reported. Regioselective displacements of chlorines, as well as regioselective diazotation reactions are described, which allow the introduction of structural diversity on the scaffold by consecutive reactions. Screening of this focused libra...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2010.10.027

    authors： Jang MY,De Jonghe S,Segers K,Anné J,Herdewijn P

    更新日期：2011-01-01 00:00:00

  • Development of a liposomal delivery system for temperature-triggered release of a tumor targeting agent, Ln(III)-DOTA-phenylboronate.

    abstract：:Liposomes, capable of temperature-triggered content release at the site of interest, can be of great importance for imaging and therapy of tumors. The delivery of imaging agents or therapeutics can be improved by application of liposomes with a gel-to-liquid phase-transition temperature suitable for mild hyperthermia ...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2010.06.036

    authors： Djanashvili K,ten Hagen TL,Blangé R,Schipper D,Peters JA,Koning GA

    更新日期：2011-02-01 00:00:00

  • Conformational control of cyclosporin through substitution of the N-5 position. A new class of cyclosporin antagonists.

    abstract：:Cyclosporin A (CsA) can be regiospecifically alkylated at the NH of Val-5 with reactive bromides in the presence of phosphazene-base P4-t-Bu to yield derivatives 2-5. These are devoid of immunosuppressive activity in vitro but they have binding affinity for cyclophilin A (CypA) similar to that of CsA and thus represen...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/s0968-0896(96)00204-0

    authors： Papageorgiou C,Kallen J,France J,French R

    更新日期：1997-01-01 00:00:00

  • An LP1 analogue, selective MOR agonist with a peculiar pharmacological profile, used to scrutiny the ligand binding domain.

    abstract：:The hypothesis that central analgesia with reduced side effects is obtainable by occupying an 'allosteric' site in the MOR ligand binding domain requires the development of new ligands with peculiar pharmacological profile to be used as tools. New benzomorphan derivatives, analogues of LP1, a multitarget MOR agonist/D...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2016.08.057

    authors： Ronsisvalle S,Aricò G,Panarello F,Spadaro A,Pasquinucci L,Pappalardo MS,Parenti C,Ronsisvalle N

    更新日期：2016-11-01 00:00:00