Quantitative insights towards the design of potent deazaxanthine antagonists of adenosine 2B receptors.

Abstract:

:Adenosine receptors have been considered as potential targets for drug development, but one of the main obstacles to this goal is to selectively inhibit one receptor subtype over the others. This subject is particularly crucial for adenosine A2b receptor antagonists (AdoRA2B). The structure–activity relationships of xanthine derivatives which are AdoRA2B have been comprehensively investigated, but the steric and electronic requirements of deazaxanthine AdoRA2B have not been described from a quantitative standpoint of view. Herein we report our efforts to shorten this knowledge gap through 2D-QSAR (HQSAR) and 3D-QSAR (CoMFA) approaches. The good statistical quality (HQSAR--r(2) = 0.85, q(2)(LOO) = 0.77; CoMFA – r(2) = 0.86, q(2) = 0.70) and predictive ability (r(2) = (pred1) = 0.78, r(2)(pred2) = 0.78 and r(2) = (pred1) = 0.70, r(2) = (pred2) = 0.70,respectively) of the models, along with the information provided by contribution and contour maps hints their usefulness to the design of more potent 9-deazaxanthine derivatives.

authors

Paz OS,Brito CC,Castilho MS

doi

10.3109/14756366.2013.830113

subject

Has Abstract

pub_date

2014-08-01 00:00:00

pages

590-8

issue

4

eissn

1475-6366

issn

1475-6374

journal_volume

29

pub_type

杂志文章
  • Synthesis and cellular bioactivities of novel isoxazole derivatives incorporating an arylpiperazine moiety as anticancer agents.

    abstract::In our endeavour towards the development of effective anticancer therapeutics, a novel series of isoxazole-piperazine hybrids were synthesized and evaluated for their cytotoxic activities against human liver (Huh7 and Mahlavu) and breast (MCF-7) cancer cell lines. Within series, compounds 5l-o showed the most potent c...

    journal_title:Journal of enzyme inhibition and medicinal chemistry

    pub_type: 杂志文章

    doi:10.1080/14756366.2018.1504041

    authors: Çalışkan B,Sinoplu E,İbiş K,Akhan Güzelcan E,Çetin Atalay R,Banoglu E

    更新日期:2018-12-01 00:00:00

  • Using C60 fullerenes for photodynamic inactivation of mosquito iridescent viruses.

    abstract::This article describes the photodynamic inactivation of mosquito iridescent virus (MIV) Aedes flavescens in the presence of water-soluble C(60) fullerenes. It has been observed that the photodynamic inactivation of MIV for about 1 h reduces the infectious titre of the virus in large wax-moth larvae Galleria mellonella...

    journal_title:Journal of enzyme inhibition and medicinal chemistry

    pub_type: 杂志文章

    doi:10.3109/14756366.2011.601303

    authors: Rud Y,Buchatskyy L,Prylutskyy Y,Marchenko O,Senenko A,Schütze Ch,Ritter U

    更新日期:2012-08-01 00:00:00

  • Sulfonamides incorporating fluorine and 1,3,5-triazine moieties are effective inhibitors of three β-class carbonic anhydrases from Mycobacterium tuberculosis.

    abstract::A new series of fluorine containing 1,3,5-triazinyl sulfonamide derivatives obtained from cyanuric fluoride, sulfanilamide/4-aminoethylbenzenesulfonamide followed and incorporating also amin0, amino alcohol and amino acid moieties have been investigated as inhibitors of three β-carbonic anhydrases (CAs, EC 4.2.1.1) fr...

    journal_title:Journal of enzyme inhibition and medicinal chemistry

    pub_type: 杂志文章

    doi:10.3109/14756366.2013.842233

    authors: Ceruso M,Vullo D,Scozzafava A,Supuran CT

    更新日期:2014-10-01 00:00:00

  • Measurement of antioxidant ability of melatonin and serotonin by the DMPD and CUPRAC methods as trolox equivalent.

    abstract::Melatonin (N-acetyl-5-methoxytryptamine) is the chief secretory product of the pineal gland and synthesized enzymatically from serotonin (5-hydroxytryptamine). These indoleamine derivatives play an important role in the prevention of oxidative damage. In the present study, DMPD radical scavenging and cupric ion (Cu(2+...

    journal_title:Journal of enzyme inhibition and medicinal chemistry

    pub_type: 杂志文章

    doi:10.1080/14756360701626223

    authors: Gulçin I

    更新日期:2008-12-01 00:00:00

  • In vivo experimental approach to treatment against tabun poisoning.

    abstract::Organophosphorus compounds pose a potential threat to both military and civilian populations. Since post-exposure therapy has its limitations, our research was focused on the possibility of improving pretreatment in order to limit the toxic effects of tabun. We determined the protective index of various combinations o...

    journal_title:Journal of enzyme inhibition and medicinal chemistry

    pub_type: 杂志文章

    doi:10.3109/14756360903357593

    authors: Berend S,Katalinić M,Vrdoljak AL,Kovarik Z,Kuca K,Radić B

    更新日期:2010-08-01 00:00:00

  • Novel sulphonamides incorporating triazene moieties show powerful carbonic anhydrase I and II inhibitory properties.

    abstract::A series of compounds incorporating 3-(3-(2/3/4-substituted phenyl)triaz-1-en-1-yl) benzenesulfonamide moieties were synthesised and their chemical structure was confirmed by physico-chemical methods. Carbonic anhydrase (CA, EC 4.2.1.1) inhibitory effects of the compounds were evaluated against human isoforms hCA I an...

    journal_title:Journal of enzyme inhibition and medicinal chemistry

    pub_type: 杂志文章

    doi:10.1080/14756366.2019.1700240

    authors: Bilginer S,Gonder B,Gul HI,Kaya R,Gulcin I,Anil B,Supuran CT

    更新日期:2020-12-01 00:00:00

  • Design, synthesis, and in vitro antiproliferative and kinase inhibitory effects of pyrimidinylpyrazole derivatives terminating with arylsulfonamido or cyclic sulfamide substituents.

    abstract::A novel series of substituted pyrimidine compounds bearing N-phenylpyrazole and terminating with aryl and cyclic sulfonamido moiety were designed, synthesized, and evaluated in vitro as antiproliferative agents against a panel of 53 cell lines of different tissues at the NCI. Among them, compound 1d with p-chlorobenze...

    journal_title:Journal of enzyme inhibition and medicinal chemistry

    pub_type: 杂志文章

    doi:10.1080/14756366.2016.1190715

    authors: Gamal El-Din MM,El-Gamal MI,Abdel-Maksoud MS,Yoo KH,Baek D,Choi J,Lee H,Oh CH

    更新日期:2016-01-01 00:00:00

  • Donepezil + chromone + melatonin hybrids as promising agents for Alzheimer's disease therapy.

    abstract::We describe herein the design, multicomponent synthesis and biological studies of new donepezil + chromone + melatonin hybrids as potential agents for Alzheimer's disease (AD) therapy. We have identified compound 14n as promising multitarget small molecule showing strong BuChE inhibition (IC50 = 11.90 ± 0.05 nM), mode...

    journal_title:Journal of enzyme inhibition and medicinal chemistry

    pub_type: 杂志文章

    doi:10.1080/14756366.2018.1545766

    authors: Pachón-Angona I,Refouvelet B,Andrýs R,Martin H,Luzet V,Iriepa I,Moraleda I,Diez-Iriepa D,Oset-Gasque MJ,Marco-Contelles J,Musilek K,Ismaili L

    更新日期:2019-12-01 00:00:00

  • Carbonic anhydrase inhibitors: guaiacol and catechol derivatives effectively inhibit certain human carbonic anhydrase isoenzymes (hCA I, II, IX and XII).

    abstract::Carbonic anhydrases (CAs) are widespread metalloenzymes in higher vertebrates including humans. A series of phenolic compounds, including guaiacol, 4-methylguaiacol, 4-propylguaiacol, eugenol, isoeugenol, vanillin, syringaldehyde, catechol, 3-methyl catechol, 4-methyl catechol and 3-methoxy catechol were investigated ...

    journal_title:Journal of enzyme inhibition and medicinal chemistry

    pub_type: 杂志文章

    doi:10.3109/14756366.2014.956310

    authors: Scozzafava A,Passaponti M,Supuran CT,Gülçin İ

    更新日期:2015-01-01 00:00:00

  • Synthesis, spectral characterization and microbiological studies of Co(II), Ni(II) and Cu(II) complexes with some novel 20-membered macrocyclic hydrazino-1,2,4-triazole Schiff bases.

    abstract::A series of Co(II), Ni(II) and Cu(II) complexes have been synthesized by template condensation of 2,6-diformyl-4-methylphenol and 3-substituted-4-amino-5-hydrazino-1,2,4-triazole with CoCl(2).6H(2)O, NiCl(2).6H(2)O and CuCl(2).2H(2)O chlorides in 2 + 2+2 molar ratio in ethanol. These complexes were characterized by el...

    journal_title:Journal of enzyme inhibition and medicinal chemistry

    pub_type: 杂志文章

    doi:10.1080/14756360801945473

    authors: Avaji PG,Patil SA

    更新日期:2009-02-01 00:00:00

  • Synthesis and preliminary in vivo evaluation of new 2-Aryl-6-methyl-1,2-dihydro-1H-pyridin-4-ones and 2-Aryl-6-methylpiperidin-4-ols, as potential anti-amnesiant agents.

    abstract::A revisited synthesis of 2-aryl-6-methyl-1,2-dihydro-1H-pyridin-4-ones and their saturated analogues 2-aryl-6-methylpiperidin-4-ols is described. A five steps procedure, using the sulfinimine chemistry, to prepare a key intermediate beta-(6-chloronicotinic)-beta-amino ester is also reported. In vivo spontaneous workin...

    journal_title:Journal of enzyme inhibition and medicinal chemistry

    pub_type: 杂志文章

    doi:10.1080/14756360500212266

    authors: Leflemme N,Freret T,Boulouard M,Dallemagne P,Rault S

    更新日期:2005-12-01 00:00:00

  • Microwave-assisted synthesis of novel thiazolocarbazoles and evaluation as potential anticancer agents. Part III.

    abstract::Novel 6-substituted thiazolocarbazole derivatives have been synthesized under microwave irradiation via the corresponding imino-1,2,3-dithiazoles. In vitro antitumor potential of these polyheterocyclic compounds was evaluated. Among all the tested thiazolocarbazoles, compound 10 is the most effective in inhibiting cel...

    journal_title:Journal of enzyme inhibition and medicinal chemistry

    pub_type: 杂志文章

    doi:10.1080/14756360412331280491

    authors: Testard A,Picot L,Fruitier-Arnaudin I,Piot JM,Chabane H,Domon L,Thiery V,Besson T

    更新日期:2004-12-01 00:00:00

  • In-vitro biological evaluation of some ONS and NS donor Schiff's bases and their metal complexes.

    abstract::Complexes of Mn(II), Co(II), Ni(II), Cu(II), Zn(II) and Cd(II) with the Schiff bases salicylidene-o-aminothiophenol (H2L) and thiophene-o-carboxaldeneaniline (SB) have been synthesized and characterized by elemental analyses, magnetic measurements, thermogravimetric analyses as well as infrared spectra and reflectance...

    journal_title:Journal of enzyme inhibition and medicinal chemistry

    pub_type: 杂志文章

    doi:10.1080/14756360600628551

    authors: Panchal PK,Pansuriya PB,Patel MN

    更新日期:2006-08-01 00:00:00

  • Structure and biological properties of first row d-transition metal complexes with N-substituted sulfonamides.

    abstract::Cobalt (II), copper (II), nickel (II) and zinc (II) complexes with 2-hydroxy-1-naphthaldehyde derived N-substituted sulfonamides have been synthesized and the nature of bonding and structure of compounds have been deduced from physical, analytical and spectral (IR, (1)H NMR, (13)C NMR, Mass and electronic) data. An oc...

    journal_title:Journal of enzyme inhibition and medicinal chemistry

    pub_type: 杂志文章

    doi:10.1080/14756360701474913

    authors: Chohan ZH,Supuran CT

    更新日期:2008-04-01 00:00:00

  • Quinoline-based imidazole-fused heterocycles as new inhibitors of 15-lipoxygenase.

    abstract::A series of 2-chloro-quinoline-based imidazopyridines 6a-l and imidazothiazoles 6m-o bearing a bulky alkylamine side chain were synthesized as soybean 15-LOX inhibitors. The target compounds 6a-o were prepared via one-pot reaction of 2-chloroquinoline-3-carbaldehyde (3), heteroaromatic amidine 4, and alkyl isocyanides...

    journal_title:Journal of enzyme inhibition and medicinal chemistry

    pub_type: 杂志文章

    doi:10.1080/14756366.2016.1206087

    authors: Dianat S,Moghimi S,Mahdavi M,Nadri H,Moradi A,Firoozpour L,Emami S,Mouradzadegun A,Shafiee A,Foroumadi A

    更新日期:2016-01-01 00:00:00

  • Soyasaponins from Zolfino bean as aldose reductase differential inhibitors.

    abstract::Seven triterpenoid saponins were identified in methanolic extracts of seeds of the Zolfino bean landrace (Phaseolus vulgaris L.) by HPLC fractionation, revealing their ability to inhibit highly purified human recombinant aldose reductase (hAKR1B1). Six of these compounds were associated by MS analysis with the followi...

    journal_title:Journal of enzyme inhibition and medicinal chemistry

    pub_type: 杂志文章

    doi:10.1080/14756366.2018.1553166

    authors: Balestri F,De Leo M,Sorce C,Cappiello M,Quattrini L,Moschini R,Pineschi C,Braca A,La Motta C,Da Settimo F,Del-Corso A,Mura U

    更新日期:2019-12-01 00:00:00

  • New spiroindolinones bearing 5-chlorobenzothiazole moiety.

    abstract::In this study, 5-chloro-3H-spiro-[1,3-benzothiazole-2,3'-indole]-2'(1'H)-one derivatives 3a-l were synthesized by the reaction of 1H-indole-2,3-diones 1a-l with 2-amino-4-chlorothiophenol 2 in ethanol. 3a-l were tested for their abilities to inhibit lipid peroxidation (LP), scavenge DPPH(•) and ABTS(•+) radicals, and ...

    journal_title:Journal of enzyme inhibition and medicinal chemistry

    pub_type: 杂志文章

    doi:10.3109/14756366.2013.800058

    authors: Ermut G,Karalı N,Özsoy N,Can A

    更新日期:2014-08-01 00:00:00

  • Inhibitory effect of cisplatin and [Pt(dach)Cl2] on the activity of phospholipase A2.

    abstract::This work has been focused on testing the influence of two selected Pt(II) complexes cisplatin, Pt(NH₃)₂Cl₂, and [Pt(dach)Cl₂] on the activity of porcine pancreatic phospholipase A₂ (PLA₂). It has been assumed that this enzyme plays a role in carcinogenesis and that it could be a target in the tumour therapy. The resu...

    journal_title:Journal of enzyme inhibition and medicinal chemistry

    pub_type: 杂志文章

    doi:10.3109/14756366.2012.666539

    authors: Radisavljević M,Kamčeva T,Bugarčić ŽD,Petković M

    更新日期:2013-08-01 00:00:00

  • Synthesis of novel benzoxanthone analogues as non-Camptothecin topoisomerase I inhibitors.

    abstract::Structure modification of the side chain of the lead compound benzoxanthone provided a series of benzoxanthone analogues and 12 of them were first reported. The results showed that most of these compounds had moderate cytotoxicity against tumour cells with the 50% inhibition concentration in the micromolar range. Furt...

    journal_title:Journal of enzyme inhibition and medicinal chemistry

    pub_type: 杂志文章

    doi:10.3109/14756366.2011.595712

    authors: Cheng P,Zhu L,Guo W,Liu W,Yao J,Dong G,Zhang Y,Zhuang C,Sheng C,Miao Z,Zhang W

    更新日期:2012-06-01 00:00:00

  • Synthesis and biological evaluation of new 3(2H)-pyridazinone derivatives as non-toxic anti-proliferative compounds against human colon carcinoma HCT116 cells.

    abstract::Novel 3(2H)-pyridazinone derivatives were designed, synthesised in satisfactory yields and evaluated in different experimental assays to assess their preliminary toxicity in vivo and anti-proliferative effects against HCT116 cell lines in vitro. Artemia salina lethality test provided LC50 values >100 µg/mL for all com...

    journal_title:Journal of enzyme inhibition and medicinal chemistry

    pub_type: 杂志文章

    doi:10.1080/14756366.2020.1755670

    authors: Özdemir Z,Utku S,Mathew B,Carradori S,Orlando G,Di Simone S,Alagöz MA,Özçelik AB,Uysal M,Ferrante C

    更新日期:2020-12-01 00:00:00

  • Structure-activity relationships of human urotensin II and related analogues on rat aortic ring contraction.

    abstract::The sequence of human urotensin II (UII) has been recently established as H-Glu-Thr-Pro-Asp-Cys-Phe-Trp-Lys-Tyr-Cys-Val-OH, and it has been reported that UII is the most potent mammalian vasoconstrictor peptide identified so far. A series of UII analogues was synthesized, and the contractile activity of each compound ...

    journal_title:Journal of enzyme inhibition and medicinal chemistry

    pub_type: 杂志文章

    doi:10.1080/1475636031000093507

    authors: Labarrère P,Chatenet D,Leprince J,Marionneau C,Loirand G,Tonon MC,Dubessy C,Scalbert E,Pfeiffer B,Renard P,Calas B,Pacaud P,Vaudry H

    更新日期:2003-04-01 00:00:00

  • Multicomponent synthesis of some new (1S,4S)-2,5-diazabicyclo[2.2.1]heptane-dithiocarbamates and their in vitro anti-proliferative activity against CaSki, MDA-MB-231 and SK-Lu-1 tumour cells as apoptosis inducing agents without necrosis.

    abstract::Identification of a new class of antitumor agent capable to induce apoptosis without triggering necrotic cell death event is challenging. The present communication describes the multicomponent synthesis of seven new (1S,4S)-2,5-diazabicyclo[2.2.1]heptane-dithiocarbamates and their in vitro antiproliferative activity o...

    journal_title:Journal of enzyme inhibition and medicinal chemistry

    pub_type: 杂志文章

    doi:10.1080/14756366.2017.1363197

    authors: Laskar S,Sánchez-Sánchez L,López-Ortiz M,López-Muñoz H,Escobar-Sánchez ML,Sánchez AT,Regla I

    更新日期:2017-12-01 00:00:00

  • Antioxidant properties of benzylchroman derivatives from Caesalpinia sappan L. against oxidative stress evaluated in vitro.

    abstract::The antioxidant activity of extracts from Caesalpinia sappan L. (CSL) was studied in vitro by evaluating the total phenolics, measuring the antioxidant activity by TEAC, measuring the scavenging effects on reactive oxygen species (ROS) and on reactive nitrogen species (RNS), and measuring the inhibitory effect on Cu(2...

    journal_title:Journal of enzyme inhibition and medicinal chemistry

    pub_type: 杂志文章,收录出版

    doi:10.3109/14756360903373376

    authors: Lee MJ,Lee HS,Kim H,Yi HS,Park SD,Moon HI,Park WH

    更新日期:2010-10-01 00:00:00

  • Synthesis, characterization, and antimicrobial evaluation of some new hydrazinecarbothioamide, 1,2,4-triazole and 1,3,4-thiadiazole derivatives.

    abstract::In this work, we reported the synthesis and evaluation of antibacterial and antifungal activities of three new compound series obtained from 6-(phenyl/4-chlorophenyl)imidazo[2,1-b]thiazole-3-acetic acid hydrazide: 2-{[6-(phenyl/4-chlorophenyl)imidazo[2,1-b]thiazol-3-yl]acetyl}-N-alkyl/arylhydrazinecarbothioamides (2a-...

    journal_title:Journal of enzyme inhibition and medicinal chemistry

    pub_type: 杂志文章

    doi:10.3109/14756366.2012.700926

    authors: Güzeldemirci NU,Satana D,Küçükbasmacı O

    更新日期:2013-10-01 00:00:00

  • Synthesis and antimalarial activity of some new 1,2-dioxolane derivatives.

    abstract::The synthesis of 1,2-dioxolane derivatives in two different acetophenone series, as simplified models of natural coumarins is described. 2-Acetyl-3-acetoxy-4-(3-hydroperoxy-3-methylbut-1-enyl)phenyl acetate and 2-acetyl-5-acetoxy4-(3-hydroperoxy-3-methylbut-1-enyl) phenyl acetate synthons are used as precursors to the...

    journal_title:Journal of enzyme inhibition and medicinal chemistry

    pub_type: 杂志文章

    doi:10.1080/1475636021000005677

    authors: Helesbeux JJ,Peyronnet D,Labaïed M,Grellier P,Frappier F,Seraphin D,Richomme P,Duval O

    更新日期:2002-12-01 00:00:00

  • Synthesis of 5-aryl-6-cinnamoyl-7-methyl-flavanones as novel antioxidants and antihyperlipidemics.

    abstract::An economical and efficient one-pot synthesis of a series of novel 5-aryl-6-cinnamoyl-7-methyl-flavanones has been developed by simple refluxing of cinnamoyl chalcones with NaOAc in aqueous ethanol in quantitative yields. These flavanones were screened for their in vitro antioxidant and in vivo antidyslipidemic activi...

    journal_title:Journal of enzyme inhibition and medicinal chemistry

    pub_type: 杂志文章

    doi:10.3109/14756366.2011.585134

    authors: Sharma A,Anand N,Sharma R,Chaturvedi U,Khanna AK,Bhatia G,Tripathi RP

    更新日期:2012-04-01 00:00:00

  • Effect of calcium on rat intestinal alkaline phosphatase activity and molecular aggregation.

    abstract::Two fractions of rat intestinal alkaline phosphatase (IAP) were detected by Western blot: 168 +/- 6 and 475 +/- 45 kDa. The low molecular weight fraction constitutes 43% of the isolated proteins exhibiting 82% of the enzymatic activity, and a heavier fraction constitutes 57% of the isolated proteins and has 18% of the...

    journal_title:Journal of enzyme inhibition and medicinal chemistry

    pub_type: 杂志文章

    doi:10.1080/14756360600810647

    authors: Brun LR,Brance ML,Rigalli A,Puche RC

    更新日期:2006-12-01 00:00:00

  • Equations of substrate-inhibition kinetics applied to pig kidney diamine oxidase (DAO, E.C. 1.4.3.6).

    abstract::Pig kidney diamine oxidase (DAO) and other semicarbazide-sensitive amine oxidases (SSAO) show clear substrate-inhibition kinetics and a reaction-scheme mechanism based on two substrate binding sites. We evaluated several reaction scheme mechanisms with a non-linear regression program (NCSS), estimating R2, the constan...

    journal_title:Journal of enzyme inhibition and medicinal chemistry

    pub_type: 杂志文章

    doi:10.1080/14756360310001605543

    authors: Ignesti G

    更新日期:2003-12-01 00:00:00

  • In vivo antiaging effects of alkaline water supplementation.

    abstract::Telomeres length and telomerase activity are currently considered aging molecular stigmata. Water is a major requirement for our body and water should be alkaline. Recent reports have shown that aging is related to a reduced water intake. We wanted to investigate the effect of the daily intake of alkaline water on the...

    journal_title:Journal of enzyme inhibition and medicinal chemistry

    pub_type: 杂志文章

    doi:10.1080/14756366.2020.1733547

    authors: Logozzi M,Mizzoni D,Di Raimo R,Andreotti M,Macchia D,Spada M,Fais S

    更新日期:2020-12-01 00:00:00

  • Stabilization of Aspergillus parasiticus cytosine deaminase by immobilization on calcium alginate beads improved enzyme operational stability.

    abstract::Cytosine deaminase (CD) from Aspergillus parasiticus, which has half-life of 1.10 h at 37°C, was stabilized by immobilization on calcium alginate beads. The immobilized CD had pH and temperature optimum of 5 and 50°C respectively. The immobilized enzyme also stoichiometrically deaminated Cytosine and 5-fluorocytosine ...

    journal_title:Journal of enzyme inhibition and medicinal chemistry

    pub_type: 杂志文章

    doi:10.3109/14756366.2012.724406

    authors: Zanna H,Nok AJ,Ibrahim S,Inuwa HM

    更新日期:2013-12-01 00:00:00