Discovery and structure-activity relationship studies of quinolinone derivatives as potent IL-2 suppressive agents.

Abstract:

:The quinolinone skeleton has been utilized to develop various mechanism-based immune modulators. However, the effects of quinolinone derivatives on the release of T cell-associated interleukin-2 (IL-2) have not been established. In this study, a series of novel quinolinone derivatives was synthesized, and their immunosuppressive activity was evaluated by measuring suppression of IL-2 release from activated Jurkat T cells. Optimizing the three side chains around the quinolinone skeleton revealed the most active compound: 11l. This compound exhibits potent inhibitory activity toward IL-2 release in both 12-o-tetradecanoylphorbol-13-acetate (PMA)/A23187 (ionomycin) (IC50=80±10nM) and anti-CD3/CD28-stimulated Jurkat T cells (83% inhibition at 10μM) without cytotoxic effects. Further investigation into the underlying mechanism of 11l indicated the suppression of NF-κB and nuclear factor of activated T cells (NFAT) promoter activities in Jurkat T cells.

journal_name

Bioorg Med Chem

authors

Kwak SH,Kang JA,Kim M,Lee SD,Park JH,Park SG,Ko H,Kim YC

doi

10.1016/j.bmc.2016.08.051

subject

Has Abstract

pub_date

2016-11-01 00:00:00

pages

5357-5367

issue

21

eissn

0968-0896

issn

1464-3391

pii

S0968-0896(16)30668-X

journal_volume

24

pub_type

杂志文章
  • The chemoenzymatic synthesis of neoglycolipids and lipid-linked oligosaccharides using glycosyltransferases.

    abstract::The application of glycosyltransferases to the chemoenzymatic synthesis of neoglycosphingolipids and lipid-linked oligosaccharides allows the regio- and stereoselective formation of glycosidic bonds. In our laboratory galactosyl-, sialyl-, and fucosyltransferases have been used to assemble oligosaccharide headgroups d...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/s0968-0896(00)82075-1

    authors: Flitsch SL,Goodridge DM,Guilbert B,Revers L,Webberley MC,Wilson IB

    更新日期:1994-11-01 00:00:00

  • 3-Amino-2(5H)furanones as inhibitors of subgenomic hepatitis C virus RNA replication.

    abstract::A new class of compounds able to block the replication of subgenomic HCV RNA in liver cells is described. 3-Amino-2(5H)furanones 4 may be regarded as diketoacid analogues and were obtained by basic rearrangement of the isoxazolidine nucleus. ...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2008.09.006

    authors: Iannazzo D,Piperno A,Romeo G,Romeo R,Chiacchio U,Rescifina A,Balestrieri E,Macchi B,Mastino A,Cortese R

    更新日期:2008-11-01 00:00:00

  • 6-amino-4-oxo-1,3-diphenyl-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carbonyl derivatives as a new class of potent inhibitors of Interleukin-8-induced neutrophil chemotaxis.

    abstract::A series of 6-amino-4-oxo-1,3-diphenyl-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carbonyl derivatives was synthesized. The compounds demonstrated to be novel, potent and selective inhibitors of Interleukin-8-induced human neutrophil chemotaxis. A SAR study was performed by varying the carbonyl function at position 5 and...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2009.04.006

    authors: Cesarini S,Spallarossa A,Ranise A,Bruno O,Arduino N,Bertolotto M,Dallegri F,Tognolini M,Gobbetti T,Barocelli E

    更新日期:2009-05-15 00:00:00

  • Synthesis and biological evaluation of pyrimidine derivatives as novel human Pin1 inhibitors.

    abstract::Pin1 (Protein interacting with NIMA1) is a cis-trans isomerase and promotes the amide bond rotation of phosphoSer/Thr-Pro motifs in its substrates. Inhibition of Pin1 might be a novel strategy for developing anticancer agents. Herein, a series of pyrimidine derivatives were synthesized and their Pin1 inhibitory activi...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2018.03.024

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

    更新日期:2018-05-01 00:00:00

  • Metallocene-based antimalarials: an exploration into the influence of the ferrocenyl moiety on in vitro antimalarial activity in chloroquine-sensitive and chloroquine-resistant strains of Plasmodium falciparum.

    abstract::To establish the role of the ferrocenyl moiety in the antiplasmodial activity of ferroquine, compounds in which this moiety is replaced by the corresponding ruthenium-based moieties were synthesized and evaluated. In both the sensitive (D10) and resistant (K1) strains of Plasmodium falciparum, ruthenoquine analogues s...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2007.07.012

    authors: Blackie MA,Beagley P,Croft SL,Kendrick H,Moss JR,Chibale K

    更新日期:2007-10-15 00:00:00

  • Synthesis, molecular docking and biological evaluation of N,N-disubstituted 2-aminothiazolines as a new class of butyrylcholinesterase and carboxylesterase inhibitors.

    abstract::A series of 31 N,N-disubstituted 2-amino-5-halomethyl-2-thiazolines was designed, synthesized, and evaluated for inhibitory potential against acetylcholinesterase (AChE), butyrylcholinesterase (BChE) and carboxylesterase (CaE). The compounds did not inhibit AChE; the most active compounds inhibited BChE and CaE with I...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2016.01.031

    authors: Makhaeva GF,Boltneva NP,Lushchekina SV,Serebryakova OG,Stupina TS,Terentiev AA,Serkov IV,Proshin AN,Bachurin SO,Richardson RJ

    更新日期:2016-03-01 00:00:00

  • Pharmacophore-based discovery of FXR-agonists. Part II: identification of bioactive triterpenes from Ganoderma lucidum.

    abstract::The farnesoid X receptor (FXR) belonging to the metabolic subfamily of nuclear receptors is a ligand-induced transcriptional activator. Its central function is the physiological maintenance of bile acid homeostasis including the regulation of glucose and lipid metabolism. Accessible structural information about its li...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2011.09.039

    authors: Grienke U,Mihály-Bison J,Schuster D,Afonyushkin T,Binder M,Guan SH,Cheng CR,Wolber G,Stuppner H,Guo DA,Bochkov VN,Rollinger JM

    更新日期:2011-11-15 00:00:00

  • Search for alpha-helical propensity in the receptor-bound conformation of glucagon-like peptide-1.

    abstract::To elucidate the receptor-bound conformation of glucagon-like peptide-1 (GLP-1), a series of conformationally constrained GLP-1 analogues were synthesized by introducing lactam bridges between Lys(i) and Glu(i)(+4) to form alpha-helices at various positions. The activity and affinity of these analogues to GLP-1 recept...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2008.10.006

    authors: Murage EN,Schroeder JC,Beinborn M,Ahn JM

    更新日期:2008-12-01 00:00:00

  • Structural requirements of flavonoids for nitric oxide production inhibitory activity and mechanism of action.

    abstract::To clarify the structure-activity relationships of flavonoids for nitric oxide (NO) production inhibitory activity, we examined the inhibitory effects of 73 flavonoids on NO production in lipopolysaccharide-activated mouse peritoneal macrophages. Among those flavonoids, apigenin (IC(50)=7.7 microM), diosmetin (8.9 mic...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/s0968-0896(03)00067-1

    authors: Matsuda H,Morikawa T,Ando S,Toguchida I,Yoshikawa M

    更新日期:2003-05-01 00:00:00

  • Novel curcumin analogs to overcome EGFR-TKI lung adenocarcinoma drug resistance and reduce EGFR-TKI-induced GI adverse effects.

    abstract::Curcumin (1) down-regulates the expression as well as phosphorylation of epidermal growth factor receptor (EGFR) in lung adenocarcinoma cells expressing gefitinib-resistant EGFR. Thirty-seven newly synthesized curcumin analogues including dimethoxycurcumin (2, DMC) were evaluated for their effects on EGFR expression a...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2015.02.003

    authors: Wada K,Lee JY,Hung HY,Shi Q,Lin L,Zhao Y,Goto M,Yang PC,Kuo SC,Chen HW,Lee KH

    更新日期:2015-04-01 00:00:00

  • Synthesis of heteroaromatic tropeines and heterogeneous binding to glycine receptors.

    abstract::Heteroaromatic carboxylic esters of (nor)tropine were synthesized. Tropine esters displaced [(3)H]strychnine binding to glycine receptors of rat spinal cord with low Hill slopes. Two-site displacement resulted in nanomolar IC(50,1) and micromolar IC(50,2) values, and IC(50,2)/IC(50,1) ratios up to 615 depending on the...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2009.08.029

    authors: Maksay G,Vincze Z,Nemes P

    更新日期:2009-10-01 00:00:00

  • The role of dicarbonyl compounds in non-enzymatic crosslinking: a structure-activity study.

    abstract::The Maillard reaction is a complex network of reactions that has been shown to result in the non-enzymatic crosslinking of proteins. Recent attention has focussed on the role of alpha-dicarbonyl compounds as important in vivo contributors to protein crosslinking but, despite extensive research, the molecular mechanism...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/s0968-0896(02)00564-3

    authors: Meade SJ,Miller AG,Gerrard JA

    更新日期:2003-03-20 00:00:00

  • New potent antibacterials against Gram-positive multiresistant pathogens: effects of side chain modification and chirality in linezolid-like 1,2,4-oxadiazoles.

    abstract::The effects of side chain modification and chirality in linezolid-like 1,2,4-oxadiazoles have been studied to design new potent antibacterials against Gram-positive multidrug-resistant pathogens. The adopted strategy involved a molecular modelling approach, the synthesis and biological evaluation of new designed compo...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2014.10.037

    authors: Fortuna CG,Berardozzi R,Bonaccorso C,Caltabiano G,Di Bari L,Goracci L,Guarcello A,Pace A,Palumbo Piccionello A,Pescitelli G,Pierro P,Lonati E,Bulbarelli A,Cocuzza CE,Musumarra G,Musumeci R

    更新日期:2014-12-15 00:00:00

  • The synthesis of (R)-(+)-lipoic acid using a monooxygenase-catalysed biotransformation as the key step.

    abstract::2-(2-Acetoxyethyl)cyclohexanone (4) was converted into the lactone (-)-(5) regio- and enantioselectively using 2-oxo-delta 3-4,5,5-trimethylcyclopentenyl acetyl-CoA monooxygenase, an NADPH-dependent Baeyer-Villiger monooxygenase from camphor grown Pseudomonas putida NCIMB 10007. The lactone (-)-(5) was converted into ...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/s0968-0896(96)00234-9

    authors: Adger B,Bes MT,Grogan G,McCague R,Pedragosa-Moreau S,Roberts SM,Villa R,Wan PW,Willetts AJ

    更新日期:1997-02-01 00:00:00

  • Novel BACE1 inhibitors with a non-acidic heterocycle at the P1' position.

    abstract::We have reported potent peptidic and non-peptidic BACE1 inhibitors with a hydroxymethylcarbonyl (HMC) isostere as a substrate transition-state mimic. However, our potent inhibitors possess a tetrazole ring at the P1' position. It is desirable that central nervous system (CNS) drugs do not possess an acidic moiety. In ...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2013.08.016

    authors: Suzuki K,Hamada Y,Nguyen JT,Kiso Y

    更新日期:2013-11-01 00:00:00

  • Coordination of iron ions in the form of histidinyl dinitrosyl complexes does not prevent their genotoxicity.

    abstract::Formation of dinitrosyl iron complexes (DNICs) was observed in a wide spectrum of pathophysiological conditions associated with overproduction of NO. To gain insight into the possible genotoxic effects of DNIC, we examined the interaction of histidinyl dinitrosyl iron complexes (HIS-DNIC) with DNA by means of circular...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2012.09.032

    authors: Lewandowska H,Stępkowski TM,Sadło J,Wójciuk GP,Wójciuk KE,Rodger A,Kruszewski M

    更新日期:2012-11-15 00:00:00

  • New mimics of the acetate function in pheromone-based attraction.

    abstract::Several analogues of (Z)-8-dodecenyl acetate (1a), the major pheromone component of the Oriental fruit moth, Cydia molesta, with chloroformate and lactone functional groups in place of the acetate moiety, were synthesized and investigated for their biological activity at four evaluation levels, i.e. by electroantennog...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/0968-0896(96)00029-6

    authors: Hoskovec M,Hovorka O,Kalinová B,Koutek B,Streinz L,Svatos A,Sebek P,Saman D,Vrkoc J

    更新日期:1996-03-01 00:00:00

  • Novel symmetrical ureas as modulators of protein arginine methyl transferases.

    abstract::Methylation of histone arginine residues is an epigenetic mark related to gene expression that is implicated in a variety of biological processes and can be reversed by small-molecule modulators of protein arginine methyltransferases (PRMTs). A series of symmetrical ureas, designed as analogues of the known PRMT1 inhi...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2013.01.017

    authors: Fontán N,García-Domínguez P,Álvarez R,de Lera ÁR

    更新日期:2013-04-01 00:00:00

  • Synthesis and structure based optimization of 2-(4-phenoxybenzoyl)-5-hydroxyindole as a novel CaMKII inhibitor.

    abstract::Based on 2-(4-phenoxybenzoyl)-5-hydroxyindole (2), a novel structural class of CaMKII inhibitors were synthesized and further optimized. The strong acidity of the hydroxyl group and the lipophilic group at the 4 and 6-positions were found to be necessary for strong CaMKII inhibition. Compound 25 was identified as a pr...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2012.09.048

    authors: Komiya M,Asano S,Koike N,Koga E,Igarashi J,Nakatani S,Isobe Y

    更新日期:2012-12-01 00:00:00

  • Activation of lysine-specific demethylase 1 inhibitor peptide by redox-controlled cleavage of a traceless linker.

    abstract::We have previously employed cyclization of a linear peptide as a strategy to modulate peptide function and properties, but cleavage to regenerate the linear peptide left parts of the linker structure on the peptide, interfering with its activity. Here, we focused on cyclization of a linear peptide via a "traceless" di...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2016.12.033

    authors: Amano Y,Umezawa N,Sato S,Watanabe H,Umehara T,Higuchi T

    更新日期:2017-02-01 00:00:00

  • Structural study of four-stranded quadruplex structures containing 2'-deoxy-8-(propyn-1-yl)adenosine.

    abstract::In this paper, we report the NMR structural study of two quadruplex structures formed by truncations of the human telomeric sequence and containing a modified base, namely d(AprGGGT) and d(TAprGGGT), where Apr indicates 2'-deoxy-8-(propyn-1-yl)adenosines. Both oligonucleotides have been found to form 4-fold symmetric ...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2003.11.019

    authors: Esposito V,Randazzo A,Galeone A,Varra M,Mayol L

    更新日期:2004-03-01 00:00:00

  • The design and synthesis of substituted biphenyl libraries.

    abstract::A novel scaffold system for the generation of diversity libraries has been designed which allows for rapid modification not only of functional groups, but their spatial arrangements as well. The biphenyl scaffold allows for display of three or four diverse functional groups in a wide variety of spatial arrangements de...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/0968-0896(96)00060-0

    authors: Pavia MR,Cohen MP,Dilley GJ,Dubuc GR,Durgin TL,Forman FW,Hediger ME,Milot G,Powers TS,Sucholeiki I,Zhou S,Hangauer DG

    更新日期:1996-05-01 00:00:00

  • Visual observation of G-quadruplex DNA with the label-free fluorescent probe silole with aggregation-induced emission.

    abstract::AIE molecule silole 1 could be used to detect G-quadruplex formation using an exonuclease I hydrolysis assay. This visual observation of G-quadruplexes has been successfully used in investigating multiple G-quadruplexes, including the one-stranded telomeric, c-myc, c-kit, VEGF G-quadruplexes, and a d(G(4)T(4)G(4)) int...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2009.09.040

    authors: Huang J,Wang M,Zhou Y,Weng X,Shuai L,Zhou X,Zhang D

    更新日期:2009-11-15 00:00:00

  • Synthesis and biological evaluation of epothilone A dimeric compounds.

    abstract::The preparation and biological evaluation of a novel series of dimeric epothilone A derivatives (1-6) are described. Two types of diacyl spacers were introduced to establish the various dimeric epothilone A constructs. The effect of these compounds on tubulin polymerization and their cytotoxicity against four differen...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2009.09.032

    authors: Passarella D,Comi D,Cappelletti G,Cartelli D,Gertsch J,Quesada AR,Borlak J,Altmann KH

    更新日期:2009-11-01 00:00:00

  • Synthesis and biological evaluation of novel pyrazolyl-2,4-thiazolidinediones as anti-inflammatory and neuroprotective agents.

    abstract::Novel pyrazolyl-2,4-thiazolidinediones were prepared via the reaction of appropriate pyrazolecarboxaldehydes with 2,4-thiazolidinediones and substituted benzyl-2,4-thiazolidinediones. The resultant compounds were first evaluated for their anti-inflammatory and neuroprotective properties in vitro. The active compounds ...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2010.01.021

    authors: Youssef AM,White MS,Villanueva EB,El-Ashmawy IM,Klegeris A

    更新日期:2010-03-01 00:00:00

  • Chemical mechanisms underlying the vasodilator and platelet anti-aggregating properties of S-nitroso-N-acetyl-DL-penicillamine and S-nitrosoglutathione.

    abstract::The chemistries of S-nitroso-DL-penicillamine (SNAP) and S-nitrosoglutathione (GSNO) in relation to their ability to relax vascular smooth muscle and prevent platelet aggregation have been investigated. Metal ion catalysis greatly accelerates the decomposition of SNAP, but has little effect on GSNO. Instead, NO releas...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/0968-0896(94)00139-t

    authors: Askew SC,Butler AR,Flitney FW,Kemp GD,Megson IL

    更新日期:1995-01-01 00:00:00

  • Synthesis and optical properties of pyrrolidinyl peptide nucleic acid bearing a base discriminating fluorescence nucleobase 8-(pyrene-1-yl)-ethynyladenine.

    abstract::A combination of fluorophore and nucleobase through a π-conjugated rigid linker integrates the base pairing and the fluorescence change into a single event. Such base discriminating fluorophore can change its fluorescence as a direct response to the base pairing event and therefore have advantages over tethered labels...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2017.10.008

    authors: Nim-Anussornkul D,Vilaivan T

    更新日期:2017-12-15 00:00:00

  • A laccase-catalysed one-pot synthesis of aminonaphthoquinones and their anticancer activity.

    abstract::Nuclear monoamination of a 1,4-naphthohydroquinone with primary aromatic amines was catalysed by the commercial laccase, Novozym 51003, from Novozymes to afford aminonaphthoquinones. The synthesis was accomplished by reacting a mixture of the primary amine and 1,4-naphthohydroquinone in succinate-lactate buffer and a ...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2012.05.028

    authors: Wellington KW,Kolesnikova NI

    更新日期:2012-07-15 00:00:00

  • Synthesis and antitumor activity of 20-O-linked nitrogen-based camptothecin ester derivatives.

    abstract::A series of nitrogen-based 20S-hydroxyl camptothecin ester derivatives were prepared. 3-Aminopropionate of camptothecin was found more cytotoxic in vitro on several human tumor cell lines than 3-amidopropionate of camptothecin. Ester 16 showed best antitumor activity in vivo and in vitro in all esters we prepared. ...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2004.04.023

    authors: Wang CY,Pan XD,Liu HY,Fu ZD,Wei XY,Yang LX

    更新日期:2004-07-01 00:00:00

  • Optimization of piperidine constructed peptidyl derivatives as proteasome inhibitors.

    abstract::A series of non-covalent piperidine-containing peptidyl derivatives with various substituents at side chains of different residues were designed, synthesized and evaluated as proteasome inhibitors. After proteasome inhibitory evaluations of all the synthesized target compounds, selected ones were tested for their anti...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2020.115867

    authors: Zhao Y,Xu L,Zhang J,Zhang M,Lu J,He R,Xi J,Zhuang R,Li J,Zhou Y

    更新日期:2021-01-01 00:00:00