当前位置： SCI文献检索 > EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY期刊下所有文献 > Pharmacophore guided discovery of small-molecule interleukin 15 inhibitors.

Pharmacophore guided discovery of small-molecule interleukin 15 inhibitors.

Abstract：

:Upregulation of interleukin 15 (IL-15) contributes directly i.a. to the development of inflammatory and autoimmune diseases. Selective blockade of IL-15 aimed to treat rheumatoid arthritis, psoriasis and other IL-15-related disorders has been recognized as an efficient therapeutic method. The aim of the study was to identify small molecules which would interact with IL-15 or its receptor IL-15Rα and inhibit the cytokine's activity. Based on the crystal structure of IL-15Rα·IL-15, we created pharmacophore models to screen the ZINC database of chemical compounds for potential IL-15 and IL-15Rα inhibitors. Twenty compounds with the highest predicted binding affinities were subjected to in vitro analysis using human peripheral blood mononuclear cells to validate in silico data. Twelve molecules efficiently reduced IL-15-dependent TNF-α and IL-17 synthesis. Among these, cefazolin - a safe first-generation cephalosporin antibiotic - holds the highest promise for IL-15-directed therapeutic applications.

journal_name

Eur J Med Chem

journal_title

European journal of medicinal chemistry

authors

Żyżyńska-Granica B,Trzaskowski B,Niewieczerzał S,Filipek S,Zegrocka-Stendel O,Dutkiewicz M,Krzeczyński P,Kowalewska M,Koziak K

doi

10.1016/j.ejmech.2017.05.034

subject

Has Abstract

pub_date

2017-08-18 00:00:00

pages

543-547

eissn

0223-5234

issn

1768-3254

pii

S0223-5234(17)30395-1

journal_volume

136

pub_type

杂志文章

相关文献

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY文献大全
  • Synthesis of spirolactone-type diterpenoid derivatives from kaurene-type oridonin with improved antiproliferative effects and their apoptosis-inducing activity in human hepatoma Bel-7402 cells.

    abstract：:A series of novel spirolactone-type diterpenoid derivatives of oridonin (12a-j) were designed and synthesized. All the target compounds showed improved anti-proliferative activity against a panel of human cancer cell lines and the most effective compound 12j was more potent than positive control Taxol in K562 and Bel-...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2012.11.002

    authors： Li D,Cai H,Jiang B,Liu G,Wang Y,Wang L,Yao H,Wu X,Sun Y,Xu J

    更新日期：2013-01-01 00:00:00

  • Application of (quantitative) structure-activity relationships to progestagens: from serendipity to structure-based design.

    abstract：:Progestagens are drugs, which are widely used in hormonal contraception and in hormone-replacement therapy. Since the natural hormone, progesterone, lacks oral activity, much effort has been devoted to finding analogues with improved oral activity and, preferably, higher potency and selectivity. A crystal structure of...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章,评审

    doi：10.1016/s0223-5234(00)00168-9

    authors： Bursi R,Groen MB

    更新日期：2000-09-01 00:00:00

  • Pharmacophore-based virtual screening and Bayesian model for the identification of potential human leukotriene A4 hydrolase inhibitors.

    abstract：:Leukotriene A4 hydrolase (LTA4H), an enzyme involved in the conversion of LTA4 to LTB4, is an emerging and important anti-inflammatory target. This study demonstrates the development of quantitative pharmacophore hypothesis and Bayesian model and their applications in identification of potential human LTA4H (hLTA4H) i...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2011.02.007

    authors： Thangapandian S,John S,Sakkiah S,Lee KW

    更新日期：2011-05-01 00:00:00

  • Doing the methylene shuffle--further insights into the inhibition of mitotic kinesin Eg5 with S-trityl L-cysteine.

    abstract：:S-Trityl L-cysteine (STLC) is an inhibitor of the mitotic kinesin Eg5 with potential as an antimitotic chemotherapeutic agent. We previously reported the crystal structure of the ligand-protein complex, and now for the first time, have quantified the interactions using a molecular dynamics based approach. Based on the...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2012.05.034

    authors： Abualhasan MN,Good JA,Wittayanarakul K,Anthony NG,Berretta G,Rath O,Kozielski F,Sutcliffe OB,Mackay SP

    更新日期：2012-08-01 00:00:00

  • Photo-inducible cytotoxic and clastogenic activities of 3,6-di-substituted acridines obtained by acylation of proflavine.

    abstract：:The cytotoxicity and photo-enhanced cytotoxicity of a series of 18 3,6-di-substituted acridines were evaluated on both tumour CHO cells and human normal keratinocytes, and compared to their corresponding clastogenicity as assessed by the micronucleus assay. Compounds 2f tert-butyl N-[(6-tert-butoxycarbonylamino)acridi...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2009.01.010

    authors： Benchabane Y,Di Giorgio C,Boyer G,Sabatier AS,Allegro D,Peyrot V,De Méo M

    更新日期：2009-06-01 00:00:00

  • Discovery of 2,4-diarylaminopyrimidines bearing a resorcinol motif as novel ALK inhibitors to overcome the G1202R resistant mutation.

    abstract：:To address drug resistance caused by ALK kinase mutations, especially the most refractory and predominant mutation G1202R for the second-generation ALK inhibitor, a series of new diarylaminopyrimidine analogues were designed by incorporating a resorcinol moiety (A-ring) to interact the ALK kinase domain where the G120...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2017.12.060

    authors： Geng K,Xia Z,Ji Y,Zhang RR,Sun D,Ai J,Song Z,Geng M,Zhang A

    更新日期：2018-01-20 00:00:00

  • Epoxide-containing side chains enhance antiproliferative activity of paullones.

    abstract：:The introduction of side chains bearing epoxide motifs into the molecular scaffold of kenpaullone and 9-trifluoromethylpaullone led to improved antiproliferative activity of the novel derivatives for human tumor cell lines. The syntheses were accomplished applying Stille coupling for the introduction of unsaturated si...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2005.02.004

    authors： Xie X,Lemcke T,Gussio R,Zaharevitz DW,Leost M,Meijer L,Kunick C

    更新日期：2005-07-01 00:00:00

  • Triazole incorporated thiazoles as a new class of anticonvulsants: design, synthesis and in vivo screening.

    abstract：:Various 3-[4-(substituted phenyl)-1,3-thiazol-2-ylamino]-4-(substituted phenyl)-4,5-dihydro-1H-1,2,4-triazole-5-thiones (7a-t) were designed keeping in view the structural requirements suggested in the pharmacophore model for anticonvulsant activity. Thiazole and triazole moieties being anticonvulsants were clubbed to...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2009.12.062

    authors： Siddiqui N,Ahsan W

    更新日期：2010-04-01 00:00:00

  • Synthesis and biochemical evaluation of guanidino-alkyl-ribitol derivatives as nucleoside hydrolase inhibitors.

    abstract：:Nucleoside hydrolase (NH) is a key enzyme in the purine salvage pathway. The purine specificity of the IAG-NH from Trypanosoma vivax is at least in part due to cation-pi-stacking interactions. Guanidinium ions can be involved in cation-pi-stacking interactions, therefore a series of guanidino-alkyl-ribitol derivatives...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2007.03.027

    authors： Goeminne A,McNaughton M,Bal G,Surpateanu G,Van Der Veken P,De Prol S,Versées W,Steyaert J,Haemers A,Augustyns K

    更新日期：2008-02-01 00:00:00

  • Newly designed organotin(IV) carboxylates with peptide linkage: Synthesis, structural elucidation, physicochemical characterizations and pharmacological investigations.

    abstract：:Fourteen new organotin(IV) carboxylate complexes with peptide linkage of (2-(4-methoxy-2-nitrophenylcarbamoyl)benzoic acid) were successfully synthesized and characterized by elemental analyses, FT-IR, NMR (1H, 13C and 119Sn) and single crystal X-ray techniques. FT-IR results of the sodium salt of 2-(4-methoxy-2-nitro...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2017.11.001

    authors： Sirajuddin M,McKee V,Tariq M,Ali S

    更新日期：2018-01-01 00:00:00

  • Synthesis and biological evaluation in U87MG glioma cells of (ethynylthiophene)sulfonamido-based hydroxamates as matrix metalloproteinase inhibitors.

    abstract：:Matrix metalloproteinases (MMPs) are important factors in gliomas since these enzymes facilitate invasion into the surrounding brain and participate in neovascularization. In particular, the gelatinases (MMP-2 and MMP-9), and more recently MMP-25, have been shown to be highly expressed in gliomas and have been associa...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2011.03.033

    authors： Nuti E,Casalini F,Santamaria S,Gabelloni P,Bendinelli S,Da Pozzo E,Costa B,Marinelli L,La Pietra V,Novellino E,Margarida Bernardo M,Fridman R,Da Settimo F,Martini C,Rossello A

    更新日期：2011-07-01 00:00:00

  • Synthesis, in vitro anticancer and antibacterial activities and in silico studies of new 4-substituted 1,2,3-triazole-coumarin hybrids.

    abstract：:The 4-substituted 1,2,3-triazole core in designed coumarin hybrids (4-35) with diverse physicochemical properties was introduced by eco-friendly copper(I)-catalyzed Huisgen 1,3-dipolar cycloaddition under microwave irradiation. Coumarin-1,2,3-triazole-benzofused heterocycle hybrids emerged as the class of compounds ex...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2016.08.062

    authors： Kraljević TG,Harej A,Sedić M,Pavelić SK,Stepanić V,Drenjančević D,Talapko J,Raić-Malić S

    更新日期：2016-11-29 00:00:00

  • Synthesis, molecular docking and biological evaluation of novel phthaloyl derivatives of 3-amino-3-aryl propionic acids as inhibitors of Trypanosoma cruzi trans-sialidase.

    abstract：:In the last two decades, trans-sialidase of Trypanosoma cruzi (TcTS) has been an important pharmacological target for developing new anti-Chagas agents. In a continuous effort to discover new potential TcTS inhibitors, 3-amino-3-arylpropionic acid derivatives (series A) and novel phthaloyl derivatives (series B, C and...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2018.07.005

    authors： Kashif M,Chacón-Vargas KF,López-Cedillo JC,Nogueda-Torres B,Paz-González AD,Ramírez-Moreno E,Agusti R,Uhrig ML,Reyes-Arellano A,Peralta-Cruz J,Ashfaq M,Rivera G

    更新日期：2018-08-05 00:00:00

  • Conjugation of substituted ferrocenyl to thiadiazine as apoptosis-inducing agents targeting the Bax/Bcl-2 pathway.

    abstract：:Ferrocene compounds are a class of biologically active compounds that has antitumour and antifungal properties. This study investigated the induction of apoptosis in human fibrosarcoma cells (HT1080) after treatment with a series of 6-ferrocenyl-3-subsituted7H-1,2,4-triazolo[3,4-b]- 1,3,4-thiadiazine (FTFs). We found ...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2011.08.007

    authors： Miao R,Wei J,Lv M,Cai Y,Du Y,Hui X,Wang Q

    更新日期：2011-10-01 00:00:00

  • CODES, a novel procedure for ligand-based virtual screening: PDE7 inhibitors as an application example.

    abstract：:Phosphodiesterase (PDE) 7 is a high affinity cAMP-specific PDE whose functional role in T-cells has been the subject of some controversy. Recent findings on tissue distribution, however, support the hypothesis that PDE7 could be a good target for the treatment of airway diseases, T-cell related diseases or central ner...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2007.10.027

    authors： Castro A,Jerez MJ,Gil C,Calderón F,Doménech T,Nueda A,Martínez A

    更新日期：2008-07-01 00:00:00

  • Promising applications of steroid сonjugates for cancer research and treatment.

    abstract：:The conjugation of biologically active molecules is a powerful tool for drug discovery used to target a variety of multifunctional diseases including cancer. Conjugated drugs can provide combination therapies in a single multi-functional agent and, by doing so, be more specific and powerful than conventional classic t...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章,评审

    doi：10.1016/j.ejmech.2020.113089

    authors： А Zolottsev V,Latysheva АS,Pokrovsky VS,Khan II,Misharin AY

    更新日期：2021-01-15 00:00:00

  • Synthesis of heteroaromatic analogues of (2-aryl-1-cyclopentenyl-1-alkylidene)-(arylmethyloxy)amine COX-2 inhibitors: effects on the inhibitory activity of the replacement of the cyclopentene central core with pyrazole, thiophene or isoxazole ring.

    abstract：:Several heteroaromatic analogues of (2-aryl-1-cyclopentenyl-1-alkylidene)-(arylmethyloxy)amine COX-2 inhibitors, in which the cyclopentene moiety was replaced by pyrazole, thiophene or isoxazole ring, were synthesized, in order to verify the influence of the different nature of the central core on the COX inhibitory p...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/s0223-5234(02)01448-4

    authors： Balsamo A,Coletta I,Guglielmotti A,Landolfi C,Mancini F,Martinelli A,Milanese C,Minutolo F,Nencetti S,Orlandini E,Pinza M,Rapposelli S,Rossello A

    更新日期：2003-02-01 00:00:00

  • Synthesis and antioxidant properties of some novel 5H-dibenz[b,f]azepine derivatives in different in vitro model systems.

    abstract：:A series of 5H-dibenz[b,f]azepine containing different aminophenols and substituted aminophenols were synthesized. 3-chloro-1-(5H-dibenz[b,f]azepine-5yl)propan-1-one (2) was obtained by N-acylation of 5H-dibenz[b,f]azepine (1) with 3-chloro propionyl chloride. Further base condensation with different aminophenols and ...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2009.09.016

    authors： Vijay Kumar H,Naik N

    更新日期：2010-01-01 00:00:00

  • Bivalent bendamustine and melphalan derivatives as anticancer agents.

    abstract：:The alkylating agents bendamustine and melphalan are currently used in the treatment of various tumoral diseases. In order to increase their antitumor potency and tumor selectivity both compounds were integrated in structure-activity relationship studies including new drug carrier systems. Here we describe the synthes...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2011.02.008

    authors： Scutaru AM,Wenzel M,Gust R

    更新日期：2011-05-01 00:00:00

  • Synthesis of Abyssinone II and related compounds as potential chemopreventive agents.

    abstract：:A facile and efficient approach to the synthesis of prenylated flavonoids as potential chemopreventive agents has been described. This features the synthesis of prenyl halide, prenylation of p-hydroxybenzaldehyde, formation of prenylated polyhydroxychalcone and cyclization of prenylated polyhydroxychalcone to flavanon...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2005.09.008

    authors： Moriarty RM,Grubjesic S,Surve BC,Chandersekera SN,Prakash O,Naithani R

    更新日期：2006-02-01 00:00:00

  • Structure-based design, synthesis and biological evaluation of novel anthra[1,2-d]imidazole-6,11-dione homologues as potential antitumor agents.

    abstract：:By using fragment-based design strategies, a series of 2-thio-substituted anthra[1,2-d]imidazole-6,11-diones were synthesized and evaluated for hTERT repressing activities, cell proliferations, and NCI 60-cell panel assay. Compounds 2, 3, 4, 11, 15 and 35 were selected by the NCI and 3, 4, 11 and 15 represent the GI₅₀...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2013.06.058

    authors： Chen TC,Yu DS,Huang KF,Fu YC,Lee CC,Chen CL,Huang FC,Hsieh HH,Lin JJ,Huang HS

    更新日期：2013-11-01 00:00:00

  • Synthesis, antimalarial evaluation and molecular modeling studies of hydroxyethylpiperazines, potential aspartyl protease inhibitors, part 2.

    abstract：:The antimalarial acitivity of hydroxyethylamines, synthesized from the reaction of intermediated hydroxyethypiperazines with benzenesulfonyl chlorides or benzoyl chlorides, has been evaluated in vitro against a W2 Plasmodium falciparum clone. Some of the nineteen tested derivatives showed a significant activity in vit...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2009.03.041

    authors： Cunico W,Gomes CR,Facchinetti V,Moreth M,Penido C,Henriques MG,Varotti FP,Krettli LG,Krettli AU,da Silva FS,Caffarena ER,de Magalhães CS

    更新日期：2009-09-01 00:00:00

  • Synthesis of N6-alkyl(aryl)-2-alkyl(aryl)thioadenosines as antiplatelet agents.

    abstract：:A series of novel N(6)-alkyl(aryl)-2-alkyl(aryl)thioadenosines were synthesized, and their human antiplatelet aggregation activities were evaluated by the stimulation of adenosine 5'-diphosphate (ADP). Some of these compounds showed strong activity, among which compound 5b(11) displayed the highest activity with an IC...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2012.03.047

    authors： Liu G,Xu J,Chen N,Zhang S,Ding Z,Du H

    更新日期：2012-07-01 00:00:00

  • The design of 8-hydroxyquinoline tetracyclic lactams as HIV-1 integrase strand transfer inhibitors.

    abstract：:A novel series of HIV-1 integrase strand transfer inhibitors were designed using the venerable two-metal binding pharmacophore model and incorporating structural elements from two different literature scaffolds. This manuscript describes a number of 8-hydroxyquinoline tetracyclic lactams with exceptional antiviral act...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2016.03.038

    authors： Velthuisen EJ,Johns BA,Temelkoff DP,Brown KW,Danehower SC

    更新日期：2016-07-19 00:00:00

  • β-Ionone and its analogs as promising anticancer agents.

    abstract：:β-Ionone is an end-ring analog of β-carotenoids which widely distributed in fruit and vegetables. Recent studies have demonstrated anti-proliferative, anti-metastatic and apoptosis induction properties of β-ionone in vitro and in vivo. Also, the studies have focused on investigating the β-ionone action on different ty...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章,评审

    doi：10.1016/j.ejmech.2016.07.037

    authors： Ansari M,Emami S

    更新日期：2016-11-10 00:00:00

  • Database mining applied to central nervous system (CNS) activity.

    abstract：:A data set of 389 compounds, active in the central nervous system (CNS) and divided into eight classes according to the receptor type, was extracted from the RBI database and analyzed by Self-Organizing Maps (SOM), also known as Kohonen Artificial Neural Networks. This method gives a 2D representation of the distribut...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/s0223-5234(01)01233-8

    authors： Pintore M,Taboureau O,Ros F,Chrétien JR

    更新日期：2001-04-01 00:00:00

  • Synthesis and structure-activity relationship of 3-O-acylated (-)-epigallocatechins as 5α-reductase inhibitors.

    abstract：:A series of 3-O-acylated (-)-epigallocatechins were synthesized and their inhibition of steroid 5α-reductase was studied. They were prepared from the reaction of EGCG with tert-butyldimethylsilyl chloride followed by reductive cleavage of the ester bond. The resultant (-)-epigallocatechins penta-O-tert-butyldimethylsi...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2010.10.011

    authors： Lin SF,Lin YH,Lin M,Kao YF,Wang RW,Teng LW,Chuang SH,Chang JM,Yuan TT,Fu KC,Huang KP,Lee YS,Chiang CC,Yang SC,Lai CL,Liao CB,Chen P,Lin YS,Lai KT,Huang HJ,Yang JY,Liu CW,Wei WY,Chen CK,Hiipakka RA,Liao S

    更新日期：2010-12-01 00:00:00

  • Synthesis and biological evaluation of pyrrolo[2,3-b]pyridine analogues as antiproliferative agents and their interaction with calf thymus DNA.

    abstract：:A series of thirty two novel pyrrolo[2,3-b]pyridine analogues synthesized, characterized ((1)H NMR, (13)C NMR and MS) and cytotoxic evaluation of these molecules carried out over a panel of three human cancer cell lines including A549 (lung cancer), HeLa (cervical cancer) and MDA MB-231 (breast cancer), using sulforho...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2016.02.059

    authors： Narva S,Chitti S,Bala BR,Alvala M,Jain N,Kondapalli VG

    更新日期：2016-05-23 00:00:00

  • Development of resveratrol-curcumin hybrids as potential therapeutic agents for inflammatory lung diseases.

    abstract：:Acute lung injury (ALI) is a major cause of acute respiratory failure in critically-ill patients. Resveratrol and curcumin are proven to have potent anti-inflammatory efficacy, but their clinical application is limited by their metabolic instability. Here, a series of resveratrol and the Mono-carbonyl analogs of curcu...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2016.09.033

    authors： Pan J,Xu T,Xu F,Zhang Y,Liu Z,Chen W,Fu W,Dai Y,Zhao Y,Feng J,Liang G

    更新日期：2017-01-05 00:00:00

  • A macrolactone from benzo[a]phenazine with potent activity against Mycobacterium tuberculosis.

    abstract：:We report here an alternative to the MCPBA or ozonolysis-based oxidation methods of quinoxaline-featuring compounds prepared from beta-lapachones. The use of peracetic acid allowed a simple preparation of the corresponding macrolactones by cleavage of the ring system. These lactones were evaluated for their antimycoba...

    journal_title：European journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.ejmech.2008.06.014

    authors： Silva RS,Pinto Mdo C,Goulart MO,de Souza Filho JD,Neves I Jr,Lourenço MC,Pinto AV

    更新日期：2009-05-01 00:00:00