当前位置： SCI文献检索 > BIOORGANIC & MEDICINAL CHEMISTRY期刊下所有文献 > Synthesis and testing of azaglutamine derivatives as inhibitors of hepatitis A virus (HAV) 3C proteinase.

Synthesis and testing of azaglutamine derivatives as inhibitors of hepatitis A virus (HAV) 3C proteinase.

Abstract：

:Hepatitis A virus (HAV) 3C proteinase is a picornaviral cysteine proteinase that is essential for cleavage of the initially synthesized viral polyprotein precursor to mature fragments and is therefore required for viral replication in vivo. Since the enzyme generally recognizes peptide substrates with L-glutamine at the P1 site, four types of analogues having an azaglutamine residue were chemically synthesized: hydrazo-o-nitrophenylsulfenamides A (e.g. 16); frame-shifted hydrazo-o-nitrophenylsulfenamides B (e.g. 25-28); the azaglutamine sulfonamides C (e.g. 7, 8, 11, 12); and haloacetyl azaglutamine analogues 2 and 3. Testing of these compounds for inhibition of the HAV 3C proteinase employed a C24S mutant in which the non-essential surface cysteine was replaced with serine and which displays identical catalytic parameters to the wild-type enzyme. Sulfenamide 16 (type A) showed no significant inhibition. Sulfenamide 27 (type B) had an IC50 of ca 100 microM and gave time-dependent inactivation of the enzyme due to disulfide bond formation with the active site cysteine thiol, as demonstrated by electrospray mass spectrometry. Sulfonamide 8 (type C) was a weak competitive inhibitor with an IC50 of approximately 75 microM. The haloacetyl azaglutamine analogues 2 and 3 were time-dependent irreversible inactivators of HAV 3C proteinase with rate constants k(obs)/[I] of 680 M(-1) s(-1) and 870 M(-1) s(-1), respectively, and were shown to alkylate the active site thiol.

journal_name

Bioorg Med Chem

journal_title

Bioorganic & medicinal chemistry

authors

Huang Y,Malcolm BA,Vederas JC

doi

10.1016/s0968-0896(99)00006-1

subject

Has Abstract

pub_date

1999-04-01 00:00:00

pages

607-19

issue

4

eissn

0968-0896

issn

1464-3391

pii

S0968089699000061

journal_volume

7

pub_type

杂志文章

相关文献

BIOORGANIC & MEDICINAL CHEMISTRY文献大全
  • Synthesis and antihyperglycemic activity of suitably functionalized 3H-quinazolin-4-ones.

    abstract：:A series of 2-sec-amino-3H-quinazolin-4-ones (4a-p) and 4-sec-amino-2-chloroquinazolines (5a-b) have been synthesized by nucleophilic substitution reaction of 2-chloro-4(3H)-quinazolones (3) and 2,4-dichloroquinazolines (2) with amines, respectively. Most of the synthesized compounds were evaluated for antihyperglycem...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/s0968-0896(03)00142-1

    authors： Ram VJ,Farhanullah,Tripathi BK,Srivastava AK

    更新日期：2003-05-29 00:00:00

  • Antitumor activity and COMPARE analysis of bis-indole derivatives.

    abstract：:This paper reports the synthesis of new derivatives (formed by two indole systems separated by a central moiety) analogous of potent antitumor agents previously described. The activity of the bis-indoles bearing a pyridine core confirms the good result described in the previous paper and compound 4c was chosen for the...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2010.03.063

    authors： Andreani A,Burnelli S,Granaiola M,Leoni A,Locatelli A,Morigi R,Rambaldi M,Varoli L,Landi L,Prata C,Dalla Sega FV,Caliceti C,Shoemaker RH

    更新日期：2010-05-01 00:00:00

  • Development of polymeric drug delivery system for recognizing vascular endothelial dysfunction.

    abstract：:The vascular endothelium plays an important role in regulating vascular homeostasis. Damage to the endothelium can lead to cardiovascular diseases such as arteriosclerosis. Therefore, early-stage detection and evaluation of vascular endothelium dysfunction would be very important for effective diagnosis and therapy. W...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2008.01.006

    authors： Ikuta K,Mori T,Yamamoto T,Niidome T,Shimokawa H,Katayama Y

    更新日期：2008-03-15 00:00:00

  • Toward protein-cleaving catalytic drugs: artificial protease selective for myoglobin.

    abstract：:A protein-cleaving catalyst highly selective for a disease-related protein can be used as a catalytic drug. As the first protein-cleaving catalyst selective for a protein substrate, a catalyst for myoglobin (Mb) was designed by attaching the Cu(II) or Co(III) complex of cyclen to a binding site searched by a combinato...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/s0968-0896(03)00216-5

    authors： Jeon JW,Son SJ,Yoo CE,Hong IS,Suh J

    更新日期：2003-07-03 00:00:00

  • Synthesis and evaluation of novel 4-[(3H,3aH,6aH)-3-phenyl)-4,6-dioxo-2-phenyldihydro-2H-pyrrolo[3,4-d]isoxazol-5(3H,6H,6aH)-yl]benzoic acid derivatives as potent acetylcholinesterase inhibitors and anti-amnestic agents.

    abstract：:The present study was designed to synthesize and evaluate pyrrolo-isoxazole benzoic acid derivatives as potential acetylcholinesterase (AChE) inhibitors for the management of Alzheimer's disease. The synthesis of pyrrolo-isoxazole benzoic acid derivatives involved ring opening cyclization of p-aminobenzoic acid with m...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2011.05.027

    authors： Anand P,Singh B

    更新日期：2012-01-01 00:00:00

  • d(G3T4G4) forms unusual dimeric G-quadruplex structure with the same general fold in the presence of K+, Na+ or NH4+ ions.

    abstract：:We have recently communicated that DNA oligonucleotide d(G(3)T(4)G(4)) forms a dimeric G-quadruplex in the presence of K(+) ions [J. Am. Chem. Soc.2003, 125, 7866-7871]. The high-resolution NMR structure of d(G(3)T(4)G(4))(2) G-quadruplex exhibits G-quadruplex core consisting of three stacked G-quartets. The two overh...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2004.08.009

    authors： Sket P,Crnugelj M,Plavec J

    更新日期：2004-11-15 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

  • Discovery of potent and selective PARP-1 and PARP-2 inhibitors: SBDD analysis via a combination of X-ray structural study and homology modeling.

    abstract：:We disclose herein our efforts aimed at discovery of selective PARP-1 and PARP-2 inhibitors. We have recently discovered several novel classes of quinazolinones, quinazolidinones, and quinoxalines as potent PARP-1 inhibitors, which may represent attractive therapeutic candidates. In PARP enzyme assays using recombinan...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2005.09.061

    authors： Ishida J,Yamamoto H,Kido Y,Kamijo K,Murano K,Miyake H,Ohkubo M,Kinoshita T,Warizaya M,Iwashita A,Mihara K,Matsuoka N,Hattori K

    更新日期：2006-03-01 00:00:00

  • Inhibition of thioredoxin reductase by a novel series of bis-1,2-benzisoselenazol-3(2H)-ones: Organoselenium compounds for cancer therapy.

    abstract：:Thioredoxin reductase (TrxR) is critical for cellular redox regulation and is involved in tumor proliferation, apoptosis and metastasis. Its C-terminal redox-active center contains a cysteine (Cys497) and a unique selenocysteine (Sec498), which are exposed to solvent and easily accessible. Thus, it is becoming an impo...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2012.04.033

    authors： He J,Li D,Xiong K,Ge Y,Jin H,Zhang G,Hong M,Tian Y,Yin J,Zeng H

    更新日期：2012-06-15 00:00:00

  • Synthesis of 6-N-(benzothiazol-2-yl)deoxyadenosine and its exciton-coupled circular dichroism.

    abstract：:6-N-(Benzothiazol-2-yl)deoxyadenosine (A(BT)) was synthesized and incorporated into DNAs. Although, the multipoint benzothiazole (BT) modification of oligodeoxynucleotides reduced the stability of duplexes with their complementary strands, it induced the strong exciton coupling between BT moieties. The circular dichro...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2009.12.009

    authors： Masaki Y,Ohkubo A,Seio K,Sekine M

    更新日期：2010-01-15 00:00:00

  • Acetyl analogs of combretastatin A-4: synthesis and biological studies.

    abstract：:The combretastatins have received significant attention because of their simple chemical structures, excellent antitumor efficacy and novel antivascular mechanisms of action. Herein, we report the synthesis of 20 novel acetyl analogs of CA-4 (1), synthesized from 3,4,5-trimethoxyphenylacetone that comprises the A ring...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2011.02.018

    authors： Babu B,Lee M,Lee L,Strobel R,Brockway O,Nickols A,Sjoholm R,Tzou S,Chavda S,Desta D,Fraley G,Siegfried A,Pennington W,Hartley RM,Westbrook C,Mooberry SL,Kiakos K,Hartley JA,Lee M

    更新日期：2011-04-01 00:00:00

  • Synthesis and biological evaluation of a fluorescent analog of phenytoin as a potential inhibitor of neuropathic pain and imaging agent.

    abstract：:Here we report on a novel fluorescent analog of phenytoin as a potential inhibitor of neuropathic pain with potential use as an imaging agent. Compound 2 incorporated a heptyl side chain and dansyl moiety onto the parent compound phenytoin and produced greater displacement of BTX from sodium channels and greater funct...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2012.06.042

    authors： Walls TH,Grindrod SC,Beraud D,Zhang L,Baheti AR,Dakshanamurthy S,Patel MK,Brown ML,MacArthur LH

    更新日期：2012-09-01 00:00:00

  • Active core structure of terfestatin A, a new specific inhibitor of auxin signaling.

    abstract：:The auxins, plant hormones, regulate many aspects of the growth and development of plants. Terfestatin A (TrfA), a novel auxin signaling inhibitor, was identified in a screen of Streptomyces sp. F40 extracts for inhibition of the expression of an auxin-inducible gene. However, the mode of action of TrfA has not been e...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2008.02.085

    authors： Hayashi K,Yamazoe A,Ishibashi Y,Kusaka N,Oono Y,Nozaki H

    更新日期：2008-05-01 00:00:00

  • Heat shock proteins: A dual carrier-adjuvant for an anti-drug vaccine against heroin.

    abstract：:Heroin is a highly abused opioid that has reached epidemic status within the United States. Yet, existing therapies to treat addiction are inadequate and frequently result into rates of high recidivism. Vaccination against heroin offers a promising alternative therapeutic option but requires further development to enh...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2018.11.027

    authors： Hwang CS,Ellis B,Zhou B,Janda KD

    更新日期：2019-01-01 00:00:00

  • Tautomeric and non-tautomeric N-substituted 2-iminobenzimidazolines as new lead compounds for the design of anti-influenza drugs: An in vitro study.

    abstract：:A series of 1,3-disubstituted 2-iminobenzimidazolines as well as a number of their tautomeric analogs were synthesized. The synthesized compounds were tested for their cytotoxicity against MDCK cells and for inhibiting activity against influenza virus A/California/07/09 (H1N1)pdm09. Based on the results obtained, 50% ...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2016.09.036

    authors： Zarubaev VV,Morkovnik AS,Divaeva LN,Karpinskaya LA,Borodkin GS

    更新日期：2016-11-15 00:00:00

  • Synthesis and anticonvulsant activity of new N-Mannich bases derived from 3-(2-fluorophenyl)- and 3-(2-bromophenyl)-pyrrolidine-2,5-diones. Part II.

    abstract：:Synthesis and anticonvulsant activity of new N-Mannich bases of 3-(2-fluorophenyl)- and 3-(2-bromophenyl)-pyrrolidine-2,5-diones have been described. Initial anticonvulsant screening was performed in mice after intraperitoneal administration in the maximal electroshock seizure test (MES) and subcutaneous pentylenetetr...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2012.05.032

    authors： Obniska J,Rzepka S,Kamiński K

    更新日期：2012-08-01 00:00:00

  • Development of a platform for activatable fluorescent substrates of glucose transporters (GLUTs).

    abstract：:We have developed a platform for activatable fluorescent substrates of glucose transporters (GLUTs). We firstly conjugated fluorescein to glucosamine via an amide or methylene linker at the C-2 position of d-glucosamine, but the resulting compounds, FLG1 and FLG2, showed no uptake into MIN6 cells. So, we changed the f...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2019.02.055

    authors： Takasugi T,Hanaoka K,Sasaki A,Ikeno T,Komatsu T,Ueno T,Yamada K,Urano Y

    更新日期：2019-05-15 00:00:00

  • DNA-binding peptides searched from the solid-phase combinatorial library with the use of the magnetic beads attaching the target duplex DNA.

    abstract：:We have exhibited successful and rapid screening of DNA-binding peptide ligands from solid-phase library beads with the use of the target DNA-conjugated magnetic beads. The target duplex DNA (3) has a polyether linker between two complementary sequences (T4A3G-ether linker-CT3A4) and is stable in the duplex form durin...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/s0968-0896(99)00298-9

    authors： Alam MR,Maeda M,Sasaki S

    更新日期：2000-02-01 00:00:00

  • Synthesis and biological evaluation of new camptothecin derivatives obtained by modification of position 20.

    abstract：:The preparation and biological evaluation of a novel series of dimeric camptothecin derivatives are described. All the new compounds showed a significant ability to inhibit human tumor cell growth with IC(50) values ranging from 0.03 to 12.2 μM. The interference with the activity of the nuclear enzymes topoisomerases ...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2010.09.069

    authors： Riva E,Comi D,Borrelli S,Colombo F,Danieli B,Borlak J,Evensen L,Lorens JB,Fontana G,Gia OM,Via LD,Passarella D

    更新日期：2010-12-15 00:00:00

  • Apoptosis-inducing effect of epolactaene derivatives on BALL-1 cells.

    abstract：:Epolactaene, a neuritogenic compound in human neuroblastoma SH-SY5Y, induces apoptosis in a human leukemia B-cell line, BALL-1. The apoptosis-inducing activities of 34 epolactaene derivatives, including those of the newly synthesized alpha-alkyl-alpha,beta-epoxy-gamma-lactam derivative and cyclopropane derivatives, we...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2005.10.057

    authors： Kuramochi K,Matsui R,Matsubara Y,Nakai J,Sunoki T,Arai S,Nagata S,Nagahara Y,Mizushina Y,Ikekita M,Kobayashi S

    更新日期：2006-04-01 00:00:00

  • Structural-activity relationship study of highly-functionalized imidazolines as potent inhibitors of nuclear transcription factor-kappaB mediated IL-6 production.

    abstract：:We herein describe the synthesis and anti-inflammatory properties of a small library of imidazoline-based NF-kappaB inhibitors. The structure-activity relationship of various substituents on an imidazoline core structure was evaluated for the ability to inhibit NF-kappaB mediated IL-6 production. Optimization of the s...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2009.03.002

    authors： Kahlon DK,Lansdell TA,Fisk JS,Tepe JJ

    更新日期：2009-04-15 00:00:00

  • Factors that influence T box riboswitch efficacy and tRNA affinity.

    abstract：:The T box riboswitch is an intriguing potential target for antibacterial drug discovery. Found primarily in Gram-positive bacteria, the riboswitch regulates gene expression by selectively responding to uncharged tRNA to control transcription readthrough. Polyamines and molecular crowding are known to specifically affe...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2015.07.018

    authors： Zeng C,Zhou S,Bergmeier SC,Hines JV

    更新日期：2015-09-01 00:00:00

  • Chalcone inhibitors of the NorA efflux pump in Staphylococcus aureus whole cells and enriched everted membrane vesicles.

    abstract：:A library of 117 chalcones was screened for efflux pump inhibitory (EPI) activity against NorA mediated ethidium bromide efflux. Five of the chalcones (5-7, 9, and 10) were active and two chalcones (9 and 10) were equipotent to reserpine with IC(50)-values of 9.0 and 7.7 μM, respectively. Twenty chalcones were subsequ...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2012.05.025

    authors： Holler JG,Slotved HC,Mølgaard P,Olsen CE,Christensen SB

    更新日期：2012-07-15 00:00:00

  • Acetylesterase from orange peel as biocatalyst for the chemo- and regioselective deprotection of carbohydrates.

    abstract：:The enzyme acetylesterase from the flavedo of oranges (EC 3.1.1.6) can advantageously be applied for the chemo- and regioselective deprotection of different types of carbohydrates. It displays a selectivity which in many cases is complementary to the application of other biocatalysts or classical chemical methods. ...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/0968-0896(94)80017-0

    authors： Waldmann H,Heuser A

    更新日期：1994-06-01 00:00:00

  • Peptide T-araC conjugates: solid-phase synthesis and biological activity of N4-(acylpeptidyl)-araC.

    abstract：:Due to the capability of peptidyl derivatives of araC to behave as prodrugs of this antimetabolite, and because of the well known biological properties of peptide T and its analogues (in particular that of targeting CD4+ cells), new peptide T-araC conjugates were prepared and tested in vitro for antiproliferative acti...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/s0968-0896(99)00317-x

    authors： Manfredini S,Marastoni-M,Tomatis R,Durini E,Spisani S,Pani A,Marceddu T,Musiu C,Marongiu ME,La Colla P

    更新日期：2000-03-01 00:00:00

  • Exploration of benzamidochromenone derivatives with conformational restrictor as interleukin-5 inhibitors.

    abstract：:Novel amidochromen-4-one analogs 8a-k and 9a-f were prepared and studied for their IL-5 inhibitory activity. Among the synthesized compounds, (6-benzamido-2-cyclohexyl-4-oxo-4H-chromen-3-yl)methyl acetate (8a, 95% inhibition at 30 μM, IC50=6.1 μM) exhibited potent IL-5 inhibitory activity. The conformational restricto...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2015.03.045

    authors： Venkateswararao E,Manickam M,Boggu P,Kim Y,Jung SH

    更新日期：2015-05-15 00:00:00

  • Structural insights into binding of inhibitors to soluble epoxide hydrolase gained by fragment screening and X-ray crystallography.

    abstract：:Soluble epoxide hydrolase (sEH) is a component of the arachidonic acid cascade and is a candidate target for therapies for hypertension or inflammation. Although many sEH inhibitors are available, their scaffolds are not structurally diverse, and knowledge of their specific interactions with sEH is limited. To obtain ...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2014.03.001

    authors： Amano Y,Yamaguchi T,Tanabe E

    更新日期：2014-04-15 00:00:00

  • Lead identification and optimization of bacterial glutamate racemase inhibitors.

    abstract：:Mycobacterium tuberculosis glutamate racemase is an essential enzyme involved in peptidoglycan synthesis and conserved in most bacteria. Small molecule inhibitors were reported on other bacterial species whereas in M. tuberculosis it wasn't explored much. In this study we have screened in house compound library using ...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2017.11.031

    authors： Malapati P,Siva Krishna V,Nallangi R,Meda N,Reshma Srilakshmi R,Sriram D

    更新日期：2018-01-01 00:00:00

  • Teixobactin as a scaffold for unlimited new antimicrobial peptides: SAR study.

    abstract：:It looks that a new era of antimicrobial peptides (AMPs) started with the discovery of teixobactin, which is a "head to side-chain" cyclodepsipeptide. It was isolated from a soil gram-negative b-proteobacteria by means of a revolutionary technique. Since there, several groups have developed synthetic strategies for ef...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2017.09.040

    authors： Abdel Monaim SAH,Jad YE,El-Faham A,de la Torre BG,Albericio F

    更新日期：2018-06-01 00:00:00

  • Cembrane diterpenoids from the soft coral Sarcophyton trocheliophorum Marenzeller as a new class of PTP1B inhibitors.

    abstract：:A detailed investigation of the South China Sea soft coral Sarcophyton trocheliophorum Marenzeller yielded, along with six known terpenes (6-11), the new sarcophytonolides N-R (1-5), whose structures have been elucidated by detailed spectroscopic analysis. Sarcophytonolides N-R are mono- or bicyclic cembranoids charac...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2013.06.043

    authors： Liang LF,Gao LX,Li J,Taglialatela-Scafati O,Guo YW

    更新日期：2013-09-01 00:00:00