Purinergic receptor P2X₇: a novel target for anti-inflammatory therapy.

Abstract:

:Purinergic receptors, also known as purinoceptors, are ligand gated membrane ion channels involved in many cellular functions. Among all identified purinergic receptors, P2X₇ subform is unique since it induces the caspase activity, cytokine secretion, and apoptosis. The distribution of P2X₇ receptors, and the need of high concentration of ATP required to activate this receptor exhibited its ability to function as 'danger' sensor associated with tissue inflammation and damage. Further, the modulation of other signalling pathways associated with P2X₇ has also been proposed to play an important role in the control of macrophage functions and inflammatory responses, especially towards lipopolysaccharides. Experimentally, researchers have also observed the decreased severity of inflammatory responses in P2X₇ receptor expressing gene (P2RX₇) knockout (KO) phenotypes. Therefore, newly developed potent antagonists of P2X₇ receptor would serve as novel therapeutic agents to combat various inflammatory conditions. In this review article, we tried to explore various aspects of P2X₇ receptors including therapeutic potential, and recent discoveries and developments of P2X₇ receptor antagonists.

journal_name

Bioorg Med Chem

authors

Mehta N,Kaur M,Singh M,Chand S,Vyas B,Silakari P,Bahia MS,Silakari O

doi

10.1016/j.bmc.2013.10.054

subject

Has Abstract

pub_date

2014-01-01 00:00:00

pages

54-88

issue

1

eissn

0968-0896

issn

1464-3391

pii

S0968-0896(13)00928-0

journal_volume

22

pub_type

杂志文章,评审
  • Active site mapping of trypsin, thrombin and matriptase-2 by sulfamoyl benzamidines.

    abstract::The benzamidine moiety, a well-known arginine mimetic, has been introduced in a variety of ligands, including peptidomimetic inhibitors of trypsin-like serine proteases. According to their primary substrate specificity, the benzamidine residue interacts with the negatively charged aspartate at the bottom of the S1 poc...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2012.08.042

    authors: Dosa S,Stirnberg M,Lülsdorff V,Häußler D,Maurer E,Gütschow M

    更新日期:2012-11-01 00:00:00

  • Synthesis, biological evaluation and molecular modeling study of 2-amino-3,5-disubstituted-pyrazines as Aurora kinases inhibitors.

    abstract::Serine/threonine protein kinases Aurora A, B, and C play essential roles in cell mitosis and cytokinesis, and a number of Aurora kinase inhibitors have been evaluated in the clinic. Herein we report the synthesis and their antiproliferation of 3,5-disubstituted-2-aminopyrazines as kinases inhibitors. Amongst, 4-((3-am...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2020.115351

    authors: Bo YX,Xiang R,Xu Y,Hao SY,Wang XR,Chen SW

    更新日期:2020-03-01 00:00:00

  • Axial chirality and affinity at the GABA(A) receptor of pyrimido[1,2-a][1,4]benzodiazepines and related compounds.

    abstract::The pyrimido[1,2-a][1,4]benzodiazepines (1a-c) and the 8-membered analogues (diazocines 2a and 2b) were separated into their atropisomers with HPLC on a chiral column. High stereochemical stability was observed in the atropisomer of the 8-membered derivatives (2a and 2b), and the 1,4-benzodiazepine (1c) with 2'-chloro...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2008.09.037

    authors: Lee S,Kamide T,Tabata H,Takahashi H,Shiro M,Natsugari H

    更新日期:2008-11-01 00:00:00

  • Pleuromutilins. Part 1. The identification of novel mutilin 14-carbamates.

    abstract::A novel series of mutilin 14-carbamates has been discovered as a result of structure-activity studies on the naturally occurring antibiotic pleuromutilin (1). In particular, the 4-methoxybenzoylcarbamate, SB-222734 (15o) displays potent antibacterial activity against a number of bacterial pathogens which are resistant...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/s0968-0896(00)00338-2

    authors: Brooks G,Burgess W,Colthurst D,Hinks JD,Hunt E,Pearson MJ,Shea B,Takle AK,Wilson JM,Woodnutt G

    更新日期:2001-05-01 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

  • Cytotoxicity mechanisms of pyrazino[1,2-b]isoquinoline-4-ones and SAR studies.

    abstract::The cytotoxicity showed by 1b, an interesting representant of the title compounds, for HT-29 human colon cancer cells (CI(50) value of 1.95 x 10(-7)M) has been related to the induced cell death at the G2 phase and not to DNA damage. This compound promotes the degradation of components of the G2/M checkpoint machinery,...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2009.10.007

    authors: Ortín I,González JF,Cuesta Ede L,Manguan-García C,Perona R,Avendaño C

    更新日期:2009-12-01 00:00:00

  • Inhibitory effects of p-dodecylaminophenol on the invasiveness of human fibrosarcoma cell line HT1080.

    abstract::Cancer is a major cause of death, and the development of new anticancer drugs is urgently needed. Invasion and metastasis are the primary causes of death due to cancer rather than growth of the primary tumor. In the current study, we examined the anti-invasive effects of p-dodecylaminophenol (1), which was developed b...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2013.07.039

    authors: Takahashi N,Takeda K,Imai M

    更新日期:2013-10-01 00:00:00

  • Application of descriptors based on Lipinski's rules in the QSPR study of aqueous solubilities.

    abstract::We complement new physically interpretable descriptors inspired by the Lipinski's rules of drug bioavailability with others obtained from the Dragon 3.0 software, in order to find the best QSPR relationship for aqueous solubilities of 100 structurally heterogeneous organic, drug-like compounds. The simultaneous linear...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2007.03.044

    authors: Duchowicz PR,Talevi A,Bellera C,Bruno-Blanch LE,Castro EA

    更新日期:2007-06-01 00:00:00

  • Synthesis, structural elucidation and in vitro antiparasitic activity against Trypanosoma cruzi and Leishmania chagasi parasites of novel tetrahydro-1-benzazepine derivatives.

    abstract::Forty six new 1,4-epoxy-2-exo-aryl- and cis-2-aryl-4-hydroxytetrahydro-1-benzazepine derivatives were synthesized and fully characterized. All compounds were tested in vitro against both Trypanosoma cruzi and Leishmania chagasi parasites and also for cytotoxicity using Vero and THP-1 mammalian cell lines. Many of the ...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2010.05.018

    authors: Gómez-Ayala S,Castrillón JA,Palma A,Leal SM,Escobar P,Bahsas A

    更新日期:2010-07-01 00:00:00

  • Electronic effects of para-substitution on acetophenones in the reaction of rat liver 3alpha-hydroxysteroid dehydrogenase.

    abstract::Stereoselective reductive metabolism of various p-substituted acetophenone derivatives was studied using isolated rat liver 3alpha-hydroxysteroid dehydrogenase (3alpha-HSD). Kinetic experiments were performed and analyzed by measuring the products by HPLC using a chiral column. The results demonstrated that the presen...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2007.10.096

    authors: Uwai K,Konno N,Yasuta Y,Takeshita M

    更新日期:2008-02-01 00:00:00

  • Design, synthesis and biological evaluation of cycloalkyl arylpyrimidines (CAPYs) as HIV-1 NNRTIs.

    abstract::A series of 18 cycloalkyl arylpyrimidines (CAPYs) were designed from lead compounds diarylpyrimidines (DAPYs), synthesized and evaluated for in vitro anti-HIV activity. Among them, the compound 1p displayed potent anti-HIV-1 activity against WT HIV-1 with an EC(50) value of 0.055 μM and a selectivity index (SI) >7290....

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2011.10.002

    authors: Gu SX,Yang SQ,He QQ,Ma XD,Chen FE,Dai HF,Clercq ED,Balzarini J,Pannecouque C

    更新日期:2011-12-01 00:00:00

  • Avermectin chemistry and action: ester- and ether-type candidate photoaffinity probes.

    abstract::Avermectin B1a (1) is a potent anthelmintic, insecticide, miticide and chloride channel activator on interaction with a specific nerve membrane site analyzed by binding assays with [3H]1. Candidate photoaffinity probes were prepared replacing the dioleandrosyl substituent with potential isosteric esters and ethers app...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/s0968-0896(99)00259-x

    authors: Tsukamoto Y,Cole LM,Casida JE

    更新日期:2000-01-01 00:00:00

  • Novel antioxidant agents deriving from molecular combinations of vitamins C and E analogues: 3,4-dihydroxy-5(R).

    abstract::Molecular combinations of two antioxidants (i.e., ascorbic acid and the pharmacophore of alpha-tocopherol), namely the 2,3-dihydroxy-2,3-enono-1,4-lactone and the chromane residues, have been designed and tested for their radical scavenging activities. When evaluated for their capability to inhibit malondialdehyde (MD...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/s0968-0896(00)00205-4

    authors: Manfredini S,Vertuani S,Manfredi B,Rossoni G,Calviello G,Palozza P

    更新日期:2000-12-01 00:00:00

  • CC-1065 CBI analogs: an example of enhancement of DNA alkylation efficiency through introduction of stabilizing electrostatic interactions.

    abstract::The three trimethylammonium salts 3-5 proved to be 100 times more efficient at alkylating DNA than 2 and exhibited DNA alkylation efficiencies identical to that of (+)-CC-1065 (1). In addition, the agents 3 and 4 exhibited DNA alkylation selectivities identical to that of 2. This may be attributed to spatially well-de...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/0968-0896(95)00048-l

    authors: Boger DL,Yun W,Han N,Johnson DS

    更新日期:1995-06-01 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

  • Analogs of iso-azepinomycin as potential transition-state analog inhibitors of guanase: synthesis, biochemical screening, and structure-activity correlations of various selectively substituted imidazo[4,5-e][1,4]diazepines.

    abstract::Guanase is an important enzyme of the purine salvage pathway of nucleic acid metabolism and its inhibition has beneficial implications in viral, bacterial, and cancer therapy. The work described herein is based on a hypothesis that azepinomycin, a heterocyclic natural product and a purported transition state analog in...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2013.06.069

    authors: Tantravedi S,Chakraborty S,Shah NH,Fishbein JC,Hosmane RS

    更新日期:2013-09-01 00:00:00

  • 2-Amino diphenylsulfides as inhibitors of trypanothione reductase: modification of the side chain.

    abstract::A molecular modeling study meant to detect pharmacophore-like patterns in the active site of trypanothione reductase (TR) offered hints about the opportunity of synthesizing and testing diphenylsulfide derivatives with prolonged or branched polyamino side chains as putative TR inhibitors. The inhibition results within...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/0968-0896(96)00083-1

    authors: Baillet S,Buisine E,Horvath D,Maes L,Bonnet B,Sergheraert C

    更新日期:1996-06-01 00:00:00

  • Design and optimization of aspartate N-acetyltransferase inhibitors for the potential treatment of Canavan disease.

    abstract::Canavan disease is a fatal neurological disorder caused by defects in the metabolism of N-acetyl-l-aspartate (NAA). Recent work has shown that the devastating symptoms of this disorder are correlated with the elevated levels of NAA observed in these patients, caused as a consequence of the inability of mutated forms o...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2016.11.060

    authors: Thangavelu B,Mutthamsetty V,Wang Q,Viola RE

    更新日期:2017-02-01 00:00:00

  • Synthesis and apoptotic activity of new pyrazole derivatives in cancer cell lines.

    abstract::We designed and synthesized new pyrazole thiourea chimeric derivatives and confirmed their structures by NMR and IR spectra. Apoptotic effects were studied in human cancer cells. The N-[(1-methyl-1H-pyrazol-4-yl)carbonyl]-N'-(3-bromophenyl)-thiourea compound (4b) exhibited the highest apoptosis-inducing effect. Compou...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2015.07.010

    authors: Nitulescu GM,Draghici C,Olaru OT,Matei L,Ioana A,Dragu LD,Bleotu C

    更新日期:2015-09-01 00:00:00

  • Evaluation of fosmidomycin analogs as inhibitors of the Synechocystis sp. PCC6803 1-deoxy-D-xylulose 5-phosphate reductoisomerase.

    abstract::Analogs of the antibiotic fosmidomycin, an inhibitor of the methylerythritol phosphate pathway to isoprenoids, were synthesized and evaluated against the recombinant Synechocystis sp. PCC6803 1-deoxy-d-xylulose 5-phosphate reductoisomerase (DXR). Fosfoxacin, the phosphate analog of fosmidomycin, and its acetyl congene...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2005.11.012

    authors: Woo YH,Fernandes RP,Proteau PJ

    更新日期:2006-04-01 00:00:00

  • Mono-/dihydroxybenzoic acid esters and phenol pyridinium derivatives as inhibitors of the mammalian carbonic anhydrase isoforms I, II, VII, IX, XII and XIV.

    abstract::Using hydroxy-/dihydroxybenzoic acids as leads, a series of methyl, ethyl and iso-propyl esters of 4-hydroxy-benzoic acid, 2,4-, 2,5-, 2,6-, 3,4-, and 3,5-dihydroxybenzoic acids and of coumaric acid, were obtained and investigated for the inhibition of six mammalian carbonic anhydrase (CA, EC 4.2.1.1) isoforms, that i...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2012.05.019

    authors: Carta F,Vullo D,Maresca A,Scozzafava A,Supuran CT

    更新日期:2013-03-15 00:00:00

  • Structure-activity studies of sulfate transfer: the hydrolysis and aminolysis of 3'-phosphoadenosine 5'-phosphosulfate (PAPS).

    abstract::The pH-rate profile for the hydrolysis of 3'-phosphoadenosine 5'-phosphosulfate (PAPS) in aqueous solution has been measured. Comparison with other data suggests that hydrolysis occurs by almost complete unimolecular elimination of sulfur trioxide, with weak involvement of a molecule of water in the transition state. ...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/0968-0896(95)00015-9

    authors: Bedford CT,Kirby AJ,Logan CJ,Drummond JN

    更新日期:1995-02-01 00:00:00

  • A class of sulfonamide carbonic anhydrase inhibitors with neuropathic pain modulating effects.

    abstract::A series of benzene sulfonamide carbonic anhydrase (CA, EC 4.2.1.1) inhibitors which incorporate lipophilic 4-alkoxy- and 4-aryloxy moieties, together with several derivatives of ethoxzolamide and sulfanilamide are reported. These derivatives were investigated as inhibitors of the metalloenzyme carbonic anhydrase (CA,...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2015.02.027

    authors: Carta F,Di Cesare Mannelli L,Pinard M,Ghelardini C,Scozzafava A,McKenna R,Supuran CT

    更新日期:2015-04-15 00:00:00

  • Novel 4-acetamide-2-alkylthio-N-acetanilides resembling nimesulide: Synthesis, cell viability evaluation and in silico studies.

    abstract::Since nimesulide, a nonsteroidal anti-inflammatory drug, is known to be a selective inhibitor of cyclooxygenase-2 and shows activity against cancer cells, there has been much interest in developing related molecules with enhanced anticancer properties. Taking in consideration structural features of nimesulide analogue...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2017.06.009

    authors: Catarro M,Serrano J,Cavalheiro E,Ramos S,Santos AO,Silvestre S,Almeida P

    更新日期:2017-08-15 00:00:00

  • Synthesis of both enantiomers of hydroxypipecolic acid derivatives equivalent to 5-azapyranuronic acids and evaluation of their inhibitory activities against glycosidases.

    abstract::We have synthesized 3-hydroxy- and 3,4,5-trihydroxypipecolic acid derivatives corresponding to 5-aza derivatives of uronic acids and evaluated their inhibitory activities against various glycosidases including beta-glucuronidase. Compounds 4 and 5 were chosen as common intermediates for the synthesis of 3,4,5-trihydro...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2008.06.016

    authors: Yoshimura Y,Ohara C,Imahori T,Saito Y,Kato A,Miyauchi S,Adachi I,Takahata H

    更新日期:2008-09-01 00:00:00

  • 3-Hydroxy-1,5-dihydro-pyrrol-2-one derivatives as advanced inhibitors of HIV integrase.

    abstract::The two-metal binding model we previously reported as an inhibition mechanism of HIV integrase (HIV IN) produced a new direction in modification of 2-hydroxy-3-heteroaryl acrylic acid inhibitors (HHAAs). Here we present a novel series of HIV IN inhibitors having a 3-hydroxy-1,5-dihydro-pyrrol-2-one moiety (HDPO) as an...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2007.05.052

    authors: Kawasuji T,Fuji M,Yoshinaga T,Sato A,Fujiwara T,Kiyama R

    更新日期:2007-08-15 00:00:00

  • Synthesis and evaluation of novel modified γ-lactam prostanoids as EP4 subtype-selective agonists.

    abstract::To identify chemically and metabolically stable subtype-selective EP4 agonists, design and synthesis of a series of modified γ-lactam prostanoids has been continued. Prostanoids bearing 2-oxo-1,3-oxazolidine, 2-oxo-1,3-thiazolidine and 5-thioxopyrrolidine as a surrogate for the γ-hydroxycyclopentanone without a troubl...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2011.12.009

    authors: Kambe T,Maruyama T,Nagase T,Ogawa S,Minamoto C,Sakata K,Maruyama T,Nakai H,Toda M

    更新日期:2012-01-15 00:00:00

  • Carbon-carbon-linked (pyrazolylphenyl)oxazolidinones with antibacterial activity against multiple drug resistant gram-positive and fastidious gram-negative bacteria.

    abstract::In an effort to expand the spectrum of activity of the oxazolidinone class of antibacterial agents to include Gram-negative bacteria, a series of new carbon-carbon linked pyrazolylphenyl analogues has been prepared. The alpha-N-substituted methyl pyrazole (10alpha) in the C3-linked series exhibited very good Gram-posi...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/s0968-0896(01)00233-4

    authors: Lee CS,Allwine DA,Barbachyn MR,Grega KC,Dolak LA,Ford CW,Jensen RM,Seest EP,Hamel JC,Schaadt RD,Stapert D,Yagi BH,Zurenko GE,Genin MJ

    更新日期:2001-12-01 00:00:00

  • QSAR of 1,4-benzoxazin-3-one antimicrobials and their drug design perspectives.

    abstract::Synthetic derivatives of 1,4-benzoxazin-3-ones have been shown to possess promising antimicrobial activity, whereas their natural counterparts were found lacking in this respect. In this work, quantitative structure-activity relationships (QSAR) of natural and synthetic 1,4-benzoxazin-3-ones as antimicrobials were est...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2018.11.016

    authors: de Bruijn WJC,Hageman JA,Araya-Cloutier C,Gruppen H,Vincken JP

    更新日期:2018-12-15 00:00:00

  • Developing new chemical tools for DNA methyltransferase 1 (DNMT 1): a small-molecule activity-based probe and novel tetrazole-containing inhibitors.

    abstract::DNA methylation is an important epigenetic modification catalyzed by DNA methyltransferases (DNMTs). Abnormal expression of endogenous DNMTs in human causes alterations in the genome methylation patterns which subsequently lead to the development of cancers. Thus detection of endogenous DNMT activities and efficient i...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2015.03.006

    authors: Zhu B,Ge J,Yao SQ

    更新日期:2015-06-15 00:00:00