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


: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.


Bioorg Med Chem


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




Has Abstract


2016-11-01 00:00:00














  • Synthesis and molecular modeling of some novel hexahydroindazole derivatives as potent monoamine oxidase inhibitors.

    abstract::A novel series of 2-thiocarbamoyl-2,3,4,5,6,7-hexahydro-1H-indazole and 2-substituted thiocarbamoyl-3,3a,4,5,6,7-hexahydro-2H-indazoles derivatives were synthesized and investigated for the ability to inhibit the activity of the A and B isoforms of monoamine oxidase (MAO). The target molecules were identified on the b...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Gökhan-Kelekçi N,Simşek OO,Ercan A,Yelekçi K,Sahin ZS,Işik S,Uçar G,Bilgin AA

    更新日期:2009-09-15 00:00:00

  • Evaluation of PI polyamide conjugates with eight-base pair recognition and improvement of the aqueous solubility by PEGylation.

    abstract::To investigate the effect of elongating base-pair (bp) recognition sequences, we synthesized N-methylpyrrole-N-methylimidazole (PI) polyamide conjugates with eight-bp recognition (3-5). The DNA alkylating activities of conjugates 3-5 were evaluated by high-resolution denaturing polyacrylamide gel electrophoresis with ...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Takagaki T,Bando T,Kitano M,Hashiya K,Kashiwazaki G,Sugiyama H

    更新日期:2011-10-01 00:00:00

  • Design, synthesis and evaluation of novel quinazoline-2,4-dione derivatives as chitin synthase inhibitors and antifungal agents.

    abstract::A series of novel 1-methyl-3-substituted quinazoline-2,4-dione derivatives were designed, synthesized, and characterized by (1)H NMR, (13)C NMR and MS spectral data. Their inhibition against chitin synthase (CHS) and antifungal activities were evaluated in vitro. Results showed compounds 5b, 5c, 5e, 5f, 5j, 5k, 5l, an...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Ji Q,Yang D,Wang X,Chen C,Deng Q,Ge Z,Yuan L,Yang X,Liao F

    更新日期:2014-07-01 00:00:00

  • Photodynamic inactivation of Candida albicans using bridged polysilsesquioxane films doped with porphyrin.

    abstract::Novel photoactive bridged polysilsesquioxane films were prepared by doped with a porphyrin derivative. The films were formed by acid-catalyzed polycondensation reaction of a precursor of a bridged silsesquioxane, based on the reaction product of (glycidoxypropyl)trimethoxysilane with n-dodecylamine in the presence of ...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Alvarez MG,Gómez ML,Mora SJ,Milanesio ME,Durantini EN

    更新日期:2012-07-01 00:00:00

  • N-hydroxyethyl-piperidine and -pyrrolidine homoazasugars: preparation and evaluation of glycosidase inhibitory activity.

    abstract::An efficient and practical strategy for the synthesis of N-hydroxyethyl-1-deoxy-homonojirimycins 4 and 5 and N-hydroxyethyl-pyrrolidine homoazasugars 6 and 7 with full stereocontrol is being reported. The key step involved is the intermolecular Michael addition of benzylamine to D-glucose derived alpha,beta-unsaturate...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Dhavale DD,Matin MM,Sharma T,Sabharwal SG

    更新日期:2003-07-31 00:00:00

  • Design and synthesis of marine fungal phthalide derivatives as PPAR-γ agonists.

    abstract::On the basis of a marine fungal phthalide (paecilocin A) skeleton, we synthesized 20 analogs and evaluated them for peroxisome proliferator-activated receptor gamma (PPAR-γ) binding and activation. Among these analogs, 6 and 7 had significant PPAR-γ binding activity, and 7 showed further PPAR-γ activation in rat liver...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Xiao B,Yin J,Park M,Liu J,Li JL,Kim EL,Hong J,Chung HY,Jung JH

    更新日期:2012-08-15 00:00:00

  • Benzofuran-dihydropyridine hybrids: A new class of potential bone anabolic agents.

    abstract::A series of novel benzofuran-dihydropyridine hybrids were designed by molecular hybridization approach and evaluated for bone anabolic activities. Among the screened library, ethyl 4-(7-(sec-butyl)-2-(4-methylbenzoyl)benzofuran-5-yl)-2-methyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-carboxylate (compound 21) significant...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Modukuri RK,Choudhary D,Gupta S,Rao KB,Adhikary S,Sharma T,Siddiqi MI,Trivedi R,Sashidhara KV

    更新日期:2017-12-15 00:00:00

  • Design of a pyrene-containing fluorescence probe for labeling of RNA poly(A) tracts.

    abstract::A labeling probe containing a pyrenecarboxamide-tethered modified DNA base, (Py)U, has been developed for fluorometric detection of RNA poly(A) tracts, in which the fluorescence emission intensity was controlled by the microstructural change around (Py)U caused by binding with the target RNA. ...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Tanaka K,Okamoto A

    更新日期:2008-01-01 00:00:00

  • Design, synthesis, and biological evaluation of (E)-3-(4-methanesulfonylphenyl)-2-(aryl)acrylic acids as dual inhibitors of cyclooxygenases and lipoxygenases.

    abstract::A group of (E)-3-(4-methanesulfonylphenyl)acrylic acids possessing a substituted-phenyl ring (4-H, 4-Br, 3-Br, 4-F, 4-OH, 4-OMe, 4-OAc, and 4-NHAc) attached to the acrylic acid C-2 position were prepared using a stereospecific Perkin condensation reaction. A related group of compounds having 4- and 3-(4-isopropyloxyph...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Moreau A,Chen QH,Praveen Rao PN,Knaus EE

    更新日期:2006-12-01 00:00:00

  • A theoretical study on the structure-activity relationships of metabolites of folates as antioxidants and its implications for rational design of antioxidants.

    abstract::To elucidate the structure-activity relationships of metabolites of folates as antioxidants, the O-H bond dissociation enthalpies (BDEs) and ionization potentials (IPs) for these compounds were calculated by density functional theory (DFT) on B3LYP/6-31+G(,3pd) level. Accordingly, the antioxidant activity difference f...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Ji HF,Tang GY,Zhang HY

    更新日期:2005-02-15 00:00:00

  • Synthesis of new arylalkoxy amido derivatives as melatoninergic ligands.

    abstract::Amido derivatives 10-18 of the corresponding oxyamines were synthesised as melatoninergic ligands by the reaction of hydroxyphtalimide with the halogeno derivatives or the corresponding alcohols using Mitsunobu reaction conditions. The affinity of the compounds for chicken brain melatonin receptors and recombinant hum...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Pégurier C,Morellato L,Chahed E,Andrieux J,Nicolas JP,Boutin JA,Bennejean C,Delagrange P,Langlois M,Mathé-Allainmat M

    更新日期:2003-03-06 00:00:00

  • Substituted quinolines as noncovalent proteasome inhibitors.

    abstract::Screening of a library of diverse heterocyclic scaffolds identified substituted quinolines as inhibitors of the human proteasome. The heterocyclic library was prepared via a novel titanium-catalyzed multicomponent coupling reaction, which rendered a diverse set of isoxazoles, pyrimidines, pyrroles, pyrazoles and quino...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: McDaniel TJ,Lansdell TA,Dissanayake AA,Azevedo LM,Claes J,Odom AL,Tepe JJ

    更新日期:2016-06-01 00:00:00

  • Syntheses and pharmacological characterization of novel thiazole derivatives as potential mGluR5 PET ligands.

    abstract::Four novel thiazole containing ABP688 derivatives were synthesized and evaluated for their binding affinity towards the metabotropic glutamate receptor subtype 5 (mGluR5). (E)-3-((2-(Fluoromethyl)thiazol-4-yl)ethynyl)cyclohex-2-enone O-methyl oxime (FTECMO), the ligand with the highest binding affinity (K(i)=5.5+/-1.1...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Baumann CA,Mu L,Wertli N,Krämer SD,Honer M,Schubiger PA,Ametamey SM

    更新日期:2010-08-15 00:00:00

  • Synthesis and biological evaluation of farnesylthiosalicylamides as potential anti-tumor agents.

    abstract::Fourteen hybrids of farnesylthiosalicylic acid (FTS) with various diamines were synthesized and biologically evaluated. It was found that FTS-monoamide molecules (10a-g) displayed strong anti-proliferative activity against seven human cancer cell lines, superior to FTS and FTS-bisamide compounds (11a-g). The mono-amid...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Ling Y,Wang Z,Zhu H,Wang X,Zhang W,Wang X,Chen L,Huang Z,Zhang Y

    更新日期:2014-01-01 00:00:00

  • Synthesis and structure-activity data of some new epibatidine analogues.

    abstract::The high-pressure Diels-Alder reaction of N-carbomethyoxypyrroles and phenyl vinyl sulfone affords versatile intermediates for the palladium-catalyzed preparation of new epibatidine analogues. Structure-activity relationships of new epibatidine analogues are presented. High affinities of Ki = 0.81 and 2.6 nM for the [...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Seerden JP,Tulp MT,Scheeren HW,Kruse CG

    更新日期:1998-11-01 00:00:00

  • The hemA gene encoding glutamyl-tRNA reductase from the archaeon Methanobacterium thermoautotrophicum strain Marburg.

    abstract::In archaea the first general tetrapyrrole precursor 5-aminolevulinic acid (ALA) is formed via the tRNA-dependent five-carbon pathway from glutamate. We have cloned the hemA gene encoding the central enzyme of the pathway glutamyl-tRNA reductase from the methanogenic archaeon Methanobacterium thermoautotrophicum by com...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Hungerer C,Weiss DS,Thauer RK,Jahn D

    更新日期:1996-07-01 00:00:00

  • Synthesis and evaluation of unsaturated caprolactams as interleukin-1beta converting enzyme (ICE) inhibitors.

    abstract::Peptidomimetic compounds possessing a caprolactam ring constraint were prepared and evaluated as interleukin-1beta converting enzyme (ICE) inhibitors. The caprolactam ring was used to constrain the P3 region of our inhibitors. This strategy proved to be effective for the synthesis of ICE inhibitors, maintaining key hy...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Wang Y,O'Neil SV,Wos JA,Oppong KA,Laufersweiler MC,Soper DL,Ellis CD,Baize MW,Fancher AN,Lu W,Suchanek MK,Wang RL,Schwecke WP,Cruze CA,Buchalova M,Belkin M,De B,Demuth TP Jr

    更新日期:2007-02-01 00:00:00

  • Hole filling and library optimization: application to commercially available fragment libraries.

    abstract::Compound libraries comprise an integral component of drug discovery in the pharmaceutical and biotechnology industries. While in-house libraries often contain millions of molecules, this number pales in comparison to the accessible space of drug-like molecules. Therefore, care must be taken when adding new compounds t...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: An Y,Sherman W,Dixon SL

    更新日期:2012-09-15 00:00:00

  • Piperine analogs as potent Staphylococcus aureus NorA efflux pump inhibitors.

    abstract::Based on our recent findings that piperine is a potent Staphylococcus aureus NorA efflux pump inhibitor (EPI), 38 piperine analogs were synthesized and bioevaluated for their EPI activity. Twenty-five of them were found active with potentiating activity equivalent or more than known EPIs like reserpine, carsonic acid ...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Sangwan PL,Koul JL,Koul S,Reddy MV,Thota N,Khan IA,Kumar A,Kalia NP,Qazi GN

    更新日期:2008-11-15 00:00:00

  • Fluorine-18 (18F)-labeled retinoid x receptor (RXR) partial agonist whose tissue transferability is affected by other RXR ligands.

    abstract::Bexarotene (1), a retinoid X receptor (RXR) agonist approved for the treatment of cutaneous T cell lymphoma (CTCL), was reported to migrate into baboon brain based on findings obtained by positron emission tomography (PET) with a 11C-labeled tracer. However, co-administration of non-radioactive 1 had no effect on the ...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Takamura Y,Shibahara O,Watanabe M,Fujihara M,Yamada S,Akehi M,Sasaki T,Hirano H,Kakuta H

    更新日期:2019-07-15 00:00:00

  • Polycyclic aromatic compounds as anticancer agents: synthesis and biological evaluation of dibenzofluorene derivatives.

    abstract::Highly regioselective electrophilic substitution of dibenzofluorene was achieved and the nitro derivative was transformed to a variety of new anticancer agents. ...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Becker FF,Mukhopadhyay C,Hackfeld L,Banik I,Banik BK

    更新日期:2000-12-01 00:00:00

  • Synthesis and antimalarial evaluation of a screening library based on a tetrahydroanthraquinone natural product scaffold.

    abstract::As part of a research program aimed at discovering new antimalarial leads from Australian macrofungi a unique fungi-derived prefractionated library was screened against a chloroquine-sensitive Plasmodium falciparum line (3D7) using a radiometric growth inhibition assay. A library fraction derived from a Cortinarius sp...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Choomuenwai V,Andrews KT,Davis RA

    更新日期:2012-12-15 00:00:00

  • Characterization of chemical, radiochemical and optical properties of a dual-labeled MMP-9 targeting peptide.

    abstract::Optical imaging possesses similar sensitivity to nuclear imaging and has led to the emergence of multimodal approaches with dual-labeled nuclear/near-infrared (NIR) agents. The growing impact of (68)Ga (t(1/2)=68 min) labeled peptides on preclinical and clinical research offers a promising opportunity to merge the hig...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Azhdarinia A,Wilganowski N,Robinson H,Ghosh P,Kwon S,Lazard ZW,Davis AR,Olmsted-Davis E,Sevick-Muraca EM

    更新日期:2011-06-15 00:00:00

  • Chemoenzymatic synthesis and biological evaluation of 2- and 3-hydroxypyridine derivatives against Leishmania mexicana.

    abstract::A series of hydroxyalkyl and acyloxyalkyl derivatives of 2- and 3-hydroxypyridine was synthesized and their biological activity was evaluated as growth inhibitors of protozoan Leishmania mexicana. Thirty novel compounds were obtained through a chemoenzymatic methodology in two reaction steps. The influence of various ...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: García Liñares G,Parraud G,Labriola C,Baldessari A

    更新日期:2012-08-01 00:00:00

  • Hydroxy- or methoxy-substituted benzaldoximes and benzaldehyde-O-alkyloximes as tyrosinase inhibitors.

    abstract::Several benzaldoximes, benzaldehyde-O-ethyloximes, and acetophenonoximes were synthesized and evaluated as tyrosinase inhibitors by an assay based on tyrosinase catalyzed L-DOPA oxidation. Whereas benzaldoxime itself is only a weak inhibitor, its derivatives with one or two hydroxy or methoxy moieties in para and meta...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Ley JP,Bertram HJ

    更新日期:2001-07-01 00:00:00

  • Constituents of Brazilian red propolis and their preferential cytotoxic activity against human pancreatic PANC-1 cancer cell line in nutrient-deprived condition.

    abstract::Human pancreatic cancer cells such as PANC-1 are known to exhibit marked tolerance to nutrition starvation that enables them to survive for prolonged period of time even under extremely nutrient-deprived conditions. Thus, elimination of this tolerance to nutrition starvation is regarded as a novel approach in anticanc...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Awale S,Li F,Onozuka H,Esumi H,Tezuka Y,Kadota S

    更新日期:2008-01-01 00:00:00

  • Programmable oligomers targeting 5'-GGGG-3' in the minor groove of DNA and NF-kappaB binding inhibition.

    abstract::A series of hairpin oligomers containing benzimidazole (Bi) and imidazopyridine (Ip) rings were synthesized and screened to target 5'-WGGGGW-3', a core sequence in the DNA-binding site of NF-kappaB, a prolific transcription factor important in biology and disease. Five Bi and Ip containing oligomers bound to the 5'-WG...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Chenoweth DM,Poposki JA,Marques MA,Dervan PB

    更新日期:2007-01-15 00:00:00

  • Synthesis and biological evaluation of pyridazine derivatives as novel HIV-1 NNRTIs.

    abstract::In continuation of our efforts toward identification and optimization of novel non-nucleoside reverse transcriptase inhibitors (NNRTIs), we have employed a structure-based bioisosterism strategy, with which a new series of diarylpyridazine (DAPD) derivatives were synthesized and evaluated for their anti-HIV-1 (human i...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Li D,Zhan P,Liu H,Pannecouque C,Balzarini J,De Clercq E,Liu X

    更新日期:2013-04-01 00:00:00

  • Synthesis and cytotoxic activity of novel C7-functionalized spongiane diterpenes.

    abstract::Based on two lead cytotoxic spongiane diterpenes, a new series of C7-oxygenated derivatives were synthesized and evaluated for their antitumor activity in vitro against the cancer cell lines HeLa and HEp-2. In general, introduction of either hydroxyl or acetoxy groups at C-7 did not improve the resultant cytotoxicity,...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Arnó M,Betancur-Galvis L,González MA,Sierra J,Zaragozá RJ

    更新日期:2003-07-17 00:00:00

  • Optimization of thiazole analogues of resveratrol for induction of NAD(P)H:quinone reductase 1 (QR1).

    abstract::NAD(P)H:quinone reductase 1 (QR1) belongs to a class of enzymes called cytoprotective enzymes. It exhibits its cancer protective activity mainly by inhibiting the formation of intracellular semiquinone radicals, and by generating α-tocopherolhydroquinone, which acts as a free radical scavenger. It is therefore believe...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Mayhoub AS,Marler L,Kondratyuk TP,Park EJ,Pezzuto JM,Cushman M

    更新日期:2012-12-15 00:00:00