Activation of antibacterial prodrugs by peptide deformylase.

Abstract:

:5'-Dipeptidyl derivatives of 5-fluorodeoxyuridine (FdU) (1a-d) were synthesized. These compounds are biologically inactive but can be activated by peptide deformylase, which removes the N-terminal formyl group of the dipeptide, to release the active drug FdU via an intramolecular cyclization reaction. Because the deformylase is ubiquitous among bacteria but absent in mammalian cells, 1a-d provide a novel class of potential antibacterial agents.

journal_name

Bioorg Med Chem Lett

authors

Wei Y,Pei D

doi

10.1016/s0960-894x(00)00167-0

subject

Has Abstract

pub_date

2000-05-15 00:00:00

pages

1073-6

issue

10

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(00)00167-0

journal_volume

10

pub_type

杂志文章
  • A chromism-based assay (CHROBA) technique for in situ detection of protein kinase activity.

    abstract::A unique chromism-based assay technique (CHROBA) using photochromic spiropyran-containing peptides has been firstly established for detection of protein kinase A-catalyzed phosphorylation. The alternative method has advantages that avoid isolation and/or immobilization of kinase substrates to remove excess reagents in...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2005.01.035

    authors: Tomizaki KY,Jie X,Mihara H

    更新日期:2005-03-15 00:00:00

  • Synthesis and evaluation of furoxan-based nitric oxide-releasing derivatives of tetrahydroisoquinoline as anticancer and multidrug resistance reversal agents.

    abstract::Multidrug resistance in tumor cells poses a major obstacle to efficient chemotherapy. Several types of agents have been recognized as multidrug resistance inhibitors, among which the tetrahydroisoquinolines is the most studied. In current study 16 furoxan-based nitric oxide-releasing derivatives of tetrahydroisoquinol...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2011.07.077

    authors: Zou ZH,Lan XB,Qian H,Huang WL,Li YM

    更新日期:2011-10-01 00:00:00

  • Discovery of a synthetic dual inhibitor of HIV and HCV infection based on a tetrabutoxy-calix[4]arene scaffold.

    abstract::A potential anti-HIV and HCV drug candidate is highly desirable as coinfection has become a worldwide public health challenge. A potent compound based on a tetrabutoxy-calix[4]arene scaffold that possesses dual inhibition for both HIV and HCV is described. Structural activity relationship studies demonstrate the effec...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2010.02.043

    authors: Tsou LK,Dutschman GE,Gullen EA,Telpoukhovskaia M,Cheng YC,Hamilton AD

    更新日期:2010-04-01 00:00:00

  • Synthesis and antimalarial activity of 2-methoxyprop-2-yl peroxides derivatives.

    abstract::2-Methoxyprop-2-yl peroxides were synthesized and evaluated in vitro against Plasmodium falciparum. These acyclic artemisinin-related peroxides revealed moderate to good activity but were devoid of alkylating property towards the synthetic model of heme Mn(II)-TPP. ...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/s0960-894x(02)00837-5

    authors: Cointeaux L,Berrien JF,Peyrou V,Provot O,Ciceron L,Danis M,Robert A,Meunier B,Mayrargue J

    更新日期:2003-01-06 00:00:00

  • Fluorescence detection of serum albumin with a turnover-based sensor utilizing Kemp elimination reaction.

    abstract::The Kemp elimination reaction is a well-known chemical reaction that is facilitated on a protein surface microenvironment, and in particular is highly accelerated in a unique binding pocket of serum albumin. We have designed and synthesized a fluorescently activatable coumarin derivative with a benzisoxazole scaffold ...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2017.05.076

    authors: Sakamoto S,Komatsu T,Ueno T,Hanaoka K,Urano Y

    更新日期:2017-08-01 00:00:00

  • Triple recognition of B-DNA.

    abstract::A novel conjugate of Hoechst 33258, pyrene and neomycin was synthesized and examined for its binding and stabilization of A-T rich DNA duplexes using spectroscopic and viscometric techniques. The conjugate, containing three well known ligands that bind nucleic acids albeit in different binding modes, was found to sign...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2009.07.079

    authors: Willis B,Arya DP

    更新日期:2009-09-01 00:00:00

  • Radiosynthesis of PET radiotracer as a prodrug for imaging group II metabotropic glutamate receptors in vivo.

    abstract::Group II metabotropic glutamate receptors (mGluRs) have been implicated in a variety of neurological and psychiatric disorders in recent studies. As a noninvasive medical imaging technique and a powerful tool in neurological research, positron emission tomography (PET) offers the possibility to visualize and study gro...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2012.01.039

    authors: Wang JQ,Zhang Z,Kuruppu D,Brownell AL

    更新日期:2012-03-01 00:00:00

  • Structure-based design of isoindoline-1,3-diones and 2,3-dihydrophthalazine-1,4-diones as novel B-Raf inhibitors.

    abstract::Structure-guided design led to the discovery of novel chemical scaffolds for B-Raf inhibitors. Both type I and type II kinase inhibitors have been explored and lead compounds with good potency and excellent selectivity have been identified. ...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2011.10.012

    authors: Wang X,Salaski EJ,Berger DM,Powell D,Hu Y,Wojciechowicz D,Collins K,Frommer E

    更新日期:2011-12-01 00:00:00

  • Synthesis and HIV-1 integrase inhibitory activities of caffeoylglucosides.

    abstract::Caffeoylglucosides, which have a glucose ring as a central linker, were synthesized from methyl D-glucosides, and their anti-HIV-1 activities were tested. Among them, four dicaffeoylglucosides (IC50 = 29.1+/-35.1 microM), 6a, 6b, 9b and 10b, showed HIV-1 integrase inhibitory activity as potent as L-chicoric acid. ...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/s0960-894x(00)00355-3

    authors: Kim SN,Lee JY,Kim HJ,Shin CG,Park H,Lee YS

    更新日期:2000-08-21 00:00:00

  • A new selective fluorescent probe based on tamoxifen.

    abstract::Developing targeted validation probes that can interrogate biology is of interest for both chemists and biologists. The synthesis of suitable compounds provides a means for avoiding the costly labeling of cells with specific antibodies and the bias associated with the interpretation of biological validation experiment...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2016.09.028

    authors: Ho LA,Thomas E,McLaughlin RA,Flematti GR,Fuller RO

    更新日期:2016-10-15 00:00:00

  • Non-electrophilic modulators of the canonical Keap1/Nrf2 pathway.

    abstract::Nrf2 is the major transcription factor that regulates many of the cytoprotective enzymes involved in the adaptive stress response. Modulation of Nrf2 could be therapeutically useful in a number of disease states. Activation can occur through either an electrophilic or non-electrophilic mechanism. To date, most of the ...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章,评审

    doi:10.1016/j.bmcl.2015.04.019

    authors: Richardson BG,Jain AD,Speltz TE,Moore TW

    更新日期:2015-06-01 00:00:00

  • Chiral synthesis and pharmacological evaluation of NPS 1407: a potent, stereoselective NMDA receptor antagonist.

    abstract::The stereoselective synthesis and biological activity of NPS 1407 (4a), (S)-(-)-3-amino-1,1-bis(3-fluorophenyl)butane, a potent, stereoselective antagonist of the NMDA receptor, are described. The racemate (4) was found to be active at the NMDA receptor in an in vitro assay, prompting the synthesis of the individual s...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/s0960-894x(00)00470-4

    authors: Moe ST,Smith DL,DelMar EG,Shimizu SM,Van Wagenen BC,Balandrin MF,Chien YE,Raszkiewicz JL,Artman LD,White HS,Mueller AL

    更新日期:2000-11-06 00:00:00

  • Design, synthesis and in vitro evaluation of benzothiazole-based ureas as potential ABAD/17β-HSD10 modulators for Alzheimer's disease treatment.

    abstract::Amyloid-beta peptide (Aβ) has been recognized to interact with numerous proteins, which may lead to pathological changes in cell metabolism of Alzheimer's disease (AD) patients. One such known metabolic enzyme is mitochondrial amyloid-binding alcohol dehydrogenase (ABAD), also known as 17β-hydroxysteroid dehydrogenase...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2016.05.087

    authors: Hroch L,Benek O,Guest P,Aitken L,Soukup O,Janockova J,Musil K,Dohnal V,Dolezal R,Kuca K,Smith TK,Gunn-Moore F,Musilek K

    更新日期:2016-08-01 00:00:00

  • Design and synthesis of potent, orally-active DGAT-1 inhibitors containing a dioxino[2,3-d]pyrimidine core.

    abstract::A novel series of potent DGAT-1 inhibitors was developed originating from the lactam-based clinical candidate PF-04620110. Incorporation of a dioxino[2,3-d]pyrimidine-based core afforded good alignment of pharmacophore features and resulted in improved passive permeability. Development of an efficient, homochiral synt...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2011.08.028

    authors: Dow RL,Andrews M,Aspnes GE,Balan G,Michael Gibbs E,Guzman-Perez A,Karki K,Laperle JL,Li JC,Litchfield J,Munchhof MJ,Perreault C,Patel L

    更新日期:2011-10-15 00:00:00

  • New C-23 modified of silybin and 2,3-dehydrosilybin: synthesis and preliminary evaluation of antioxidant properties.

    abstract::Silybin is the major flavonolignan of silymarin and it displays a plethora of biological effects, generally ascribed to its antioxidant properties. Herein we shall describe an efficient synthetic strategy to obtain a variety of new and more water-soluble silybin and 2,3-dehydrosilybin (DHS) derivatives in which the 23...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2011.06.049

    authors: Zarrelli A,Sgambato A,Petito V,De Napoli L,Previtera L,Di Fabio G

    更新日期:2011-08-01 00:00:00

  • Discovery and optimization of a biphenylacetic acid series of prostaglandin D2 receptor DP2 antagonists with efficacy in a murine model of allergic rhinitis.

    abstract::Biphenylacetic acid (5) was identified through a library screen as an inhibitor of the prostaglandin D(2) receptor DP2 (CRTH2). Optimization for potency and pharmacokinetic properties led to a series of selective CRTH2 antagonists. Compounds demonstrated potency in a human DP2 binding assay and a human whole blood eos...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2011.01.024

    authors: Scott JM,Baccei C,Bain G,Broadhead A,Evans JF,Fagan P,Hutchinson JH,King C,Lorrain DS,Lee C,Prasit P,Prodanovich P,Santini A,Stearns BA

    更新日期:2011-11-01 00:00:00

  • Discovery and biological evaluation of adamantyl amide 11beta-HSD1 inhibitors.

    abstract::A series of adamantyl amide 11beta-HSD1 inhibitors has been discovered and chemically modified. Selected compounds are selective for 11beta-HSD1 over 11beta-HSD2 and possess excellent cellular potency in human and murine 11beta-HSD1 assays. Good pharmacodynamic characteristics are observed in ex vivo assays. ...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2007.02.057

    authors: Webster SP,Ward P,Binnie M,Craigie E,McConnell KM,Sooy K,Vinter A,Seckl JR,Walker BR

    更新日期:2007-05-15 00:00:00

  • Discovery of a novel melanin concentrating hormone receptor 1 (MCHR1) antagonist with reduced hERG inhibition.

    abstract::An initial SAR study resulted in the identification of the novel, potent MCHR1 antagonist 2. After further profiling, compound 2 was discovered to be a potent inhibitor of the hERG potassium channel, which prevented its further development. Additional optimization of this structure resulted in the discovery of the pot...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2012.04.006

    authors: Mihalic JT,Fan P,Chen X,Chen X,Fu Y,Motani A,Liang L,Lindstrom M,Tang L,Chen JL,Jaen J,Dai K,Li L

    更新日期:2012-06-01 00:00:00

  • Synthesis of novel benzofuran isoxazolines as protein tyrosine phosphatase 1B inhibitors.

    abstract::PTPases are considered to be involved in the etiology of diabetes mellitus and neural diseases, such as Alzheimer's disease and Parkinson's disease. Therefore, PTPase inhibitors should be useful tools to study the role of PTPases in these diseases and other biological phenomena, and which can be developed into chemoth...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2006.01.062

    authors: Ahmad G,Mishra PK,Gupta P,Yadav PP,Tiwari P,Tamrakar AK,Srivastava AK,Maurya R

    更新日期:2006-04-15 00:00:00

  • Efforts towards the optimization of a bi-aryl class of potent IRAK4 inhibitors.

    abstract::IRAK4 has been identified as potential therapeutic target for inflammatory and autoimmune diseases. Herein we report the identification and initial SAR studies of a new class of pyrazole containing IRAK4 inhibitors designed to expand chemical diversity and improve off target activity of a previously identified series....

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2016.07.048

    authors: Hanisak J,Seganish WM,McElroy WT,Tang H,Zhang R,Tsui HC,Fischmann T,Tulshian D,Tata J,Sondey C,Devito K,Fossetta J,Garlisi CG,Lundell D,Niu X

    更新日期:2016-09-01 00:00:00

  • Structure-activity relationships of trans-substituted-propenoic acid derivatives on the nicotinic acid receptor HCA2 (GPR109A).

    abstract::Nicotinic acid (niacin) has been used for decades as an antidyslipidemic drug in man. Its main target is the hydroxy-carboxylic acid receptor HCA2 (GPR109A), a G protein-coupled receptor. Other acids and esters such as methyl fumarate also interact with the receptor, which constituted the basis for the current study. ...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2010.11.091

    authors: van Veldhoven JP,Blad CC,Artsen CM,Klopman C,Wolfram DR,Abdelkadir MJ,Lane JR,Brussee J,Ijzerman AP

    更新日期:2011-05-01 00:00:00

  • 1-Amido-1-phenyl-3-piperidinylbutanes--CCR5 antagonists for the treatment of HIV: part 2.

    abstract::Optimisation of a series of 4-piperidinyltriazoles led to the identification of compound 28a which showed good whole cell antiviral activity, excellent selectivity over the hERG ion channel and complete oral absorption. ...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2009.01.008

    authors: Barber CG,Blakemore DC,Chiva JY,Eastwood RL,Middleton DS,Paradowski KA

    更新日期:2009-03-01 00:00:00

  • Synthesis and biological activity of 4-substituted benzoxazolone derivatives as a new class of sEH inhibitors with high anti-inflammatory activity in vivo.

    abstract::A series of novel 4-substituted benzoxazolone derivatives was synthesized, characterized and evaluated as human soluble epoxide hydrolase (sEH) inhibitors and anti-inflammatory agents. Some compounds showed moderate sEH inhibitory activities in vitro, and two novel compounds, 3g and 4j, exhibited the highest activitie...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2013.02.048

    authors: Tang L,Ma WH,Ma YL,Ban SR,Feng XE,Li QS

    更新日期:2013-04-15 00:00:00

  • Targeting TRAIL.

    abstract::Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), also known as Apo2L, has been investigated in the past decade for its promising anticancer activity due to its ability to selectively induce apoptosis in tumoral cells by binding to TRAIL receptors (TRAIL-R). Macromolecules such as agonistic monoclonal a...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章,评审

    doi:10.1016/j.bmcl.2019.07.053

    authors: Ion GND,Nitulescu GM,Popescu CI

    更新日期:2019-09-15 00:00:00

  • Novel and highly potent histamine H3 receptor ligands. Part 2: exploring the cyclohexylamine-based series.

    abstract::Synthesis and biological evaluation of novel and potent cyclohexylamine-based histamine H3 receptor inverse agonists are described. Compounds in this newly identified series exhibited subnanomolar binding affinities for human receptor and no significant interaction with hERG channel. One derivative (10t) demonstrated ...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2011.06.102

    authors: Labeeuw O,Levoin N,Poupardin-Olivier O,Calmels T,Ligneau X,Berrebi-Bertrand I,Robert P,Lecomte JM,Schwartz JC,Capet M

    更新日期:2011-09-15 00:00:00

  • Synthesis and immunostimulatory activity of sugar-conjugated TLR7 ligands.

    abstract::Toll-like receptors (TLRs) are a type of pattern recognition receptors (PRRs), which are activated by recognizing pathogen-associated molecular patterns (PAMPs). The activation of TLRs initiates innate immune responses and subsequently leads to adaptive immune responses. TLR agonists are effective immuomodulators in v...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2019.126840

    authors: Baba A,Wakao M,Shinchi H,Chan M,Hayashi T,Yao S,Cottam HB,Carson DA,Suda Y

    更新日期:2020-02-01 00:00:00

  • Novel BK channel openers containing dehydroabietic acid skeleton: structure-activity relationship for peripheral substituents on ring C.

    abstract::A series of dehydroabietic acid (DHAA, 2) derivatives was synthesized and evaluated as BK channel openers in an assay system of CHO-K1 cells expressing hBKalpha channels. Systematic modifications of the peripheral functionality of ring C of DHAA showed that the introduction of a nitro or (thio)urea group in ring C gre...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2008.08.078

    authors: Cui YM,Yasutomi E,Otani Y,Yoshinaga T,Ido K,Sawada K,Ohwada T

    更新日期:2008-10-01 00:00:00

  • 3-cyanoindole-based inhibitors of inosine monophosphate dehydrogenase: synthesis and initial structure-activity relationships.

    abstract::A series of novel small molecule inhibitors of inosine monophosphate dehydrogenase (IMPDH), based upon a 3-cyanoindole core, were explored. IMPDH catalyzes the rate determining step in guanine nucleotide biosynthesis and is a target for anticancer, immunosuppressive and antiviral therapy. The synthesis and the structu...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/s0960-894x(03)00757-1

    authors: Dhar TG,Shen Z,Gu HH,Chen P,Norris D,Watterson SH,Ballentine SK,Fleener CA,Rouleau KA,Barrish JC,Townsend R,Hollenbaugh DL,Iwanowicz EJ

    更新日期:2003-10-20 00:00:00

  • Microbial transformation of acetyl-11-keto-β-boswellic acid and their inhibitory activity on LPS-induced NO production.

    abstract::The capabilities of 20 strains of fungi to transform acetyl-11-keto-β-boswellic (AKBA) were screened. And biotransformation of AKBA by Cunninghamella blakesleana AS 3.970 afforded five metabolites (1-5), while two metabolites (6, 7) were isolated from biotransformation of Cunninghamella elegans AS 3.1207. The chemical...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2012.12.086

    authors: Sun Y,Liu D,Xi R,Wang X,Wang Y,Hou J,Zhang B,Wang C,Liu K,Ma X

    更新日期:2013-03-01 00:00:00

  • Enantioselective Henry (nitroaldol) reaction catalyzed by axially chiral guanidines.

    abstract::The enantioselective activation of nitroalkanes was attempted on the basis of the complexation between chiral guanidinium and nitronate through two hydrogen bonds. The proposed enantioselective activation was applied to the diastereo- and enantioselective Henry (nitroaldol) reaction of nitroalkanes with aldehydes usin...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2009.03.097

    authors: Ube H,Terada M

    更新日期:2009-07-15 00:00:00