Synthesis, structure, molecular docking, and structure-activity relationship analysis of enamines: 3-aryl-4-alkylaminofuran-2(5H)-ones as potential antibacterials.


:Thirty-one 3-aryl-4-alkylaminofuran-2(5H)-ones were designed, prepared and tested for their antibacterial activity. Some of them showed significant antibacterial activity against Gram-positive organisms, especially against Staphylococcus aureus ATCC 25923, but all were inactive against Gram-negative organisms. Out of these compounds, 3-(4-bromophenyl)-4-(2-(4-nitrophenyl)hydrazinyl)furan-2(5H)-one (4a11) showed the most potent antibacterial activity against S. aureus ATCC 25923 with MIC(50) of 0.42 μg/mL. The enzyme assay revealed that the possible antibacterial mechanism of the synthetic compounds might be due to their inhibitory activity against tyrosyl-tRNA synthetase. Molecular dockings of 4a11 into S. aureus tyrosyl-tRNA synthetase active site were also performed. This inhibitor snugly fitting the active site might well explain its excellent inhibitory activity. Meanwhile, this modeling disclosed that a more suitable optimization strategy might be to modify the benzene ring at 3-position of furanone with hydrophilic groups.


Bioorg Med Chem


Xiao ZP,He XB,Peng ZY,Xiong TJ,Peng J,Chen LH,Zhu HL




Has Abstract


2011-03-01 00:00:00














  • Synthesis and biological properties of 2-methylene-19-nor-25-dehydro-1alpha-hydroxyvitamin D(3)-26,23-lactones--weak agonists.

    abstract::In a continuing effort to explore the 2-methylene-1alpha-hydroxy-19-norvitamin D(3) class of pharmacologically important vitamin D compounds, two novel 2-methylene-19-nor-25-dehydro-1alpha-hydroxyvitamin D(3)-26,23-lactones, GC-3 and HLV, were synthesized and biologically tested. Based on reports of similarly structur...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Chiellini G,Grzywacz P,Plum LA,Barycki R,Clagett-Dame M,DeLuca HF

    更新日期:2008-09-15 00:00:00

  • The advantages of describing covalent inhibitor in vitro potencies by IC50 at a fixed time point. IC50 determination of covalent inhibitors provides meaningful data to medicinal chemistry for SAR optimization.

    abstract::Recent years have seen a resurgence in drug discovery efforts aimed at the identification of covalent inhibitors which has led to an explosion of literature reports in this area and most importantly new approved therapies. These reports and breakthroughs highlight the significant investments made across the industry i...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Thorarensen A,Balbo P,Banker ME,Czerwinski RM,Kuhn M,Maurer TS,Telliez JB,Vincent F,Wittwer AJ

    更新日期:2021-01-01 00:00:00

  • Isolation and lipolytic activity of eurycomanone and its epoxy derivative from Eurycoma longifolia.

    abstract::Eurycomanone (1) and 13β,21-epoxyeurycomanone (2) were isolated from Eurycoma longifolia for studies of lipolytic activity. Compound 1 enhanced lipolysis in adipocytes with an EC50 of 14.6μM, while its epoxy derivate, compound 2, had a stronger activity with an EC50 of 8.6μM. Based on molecular mechanistic study using...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Lahrita L,Hirosawa R,Kato E,Kawabata J

    更新日期:2017-09-01 00:00:00

  • A novel series of complexones with bis- or biazole structure as mixed ligands of paramagnetic contrast agents for MRI.

    abstract::We describe the syntheses, physicochemical properties and biological evaluation of a novel series of complexones containing bis- or biazoles moieties and two iminodiacetic acid units as novel ligands for paramagnetic lanthanides. The complexones were prepared by reaction of the corresponding 1,1'-bishaloethylbi- or bi...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Mayoral EP,García-Amo M,López P,Soriano E,Cerdán S,Ballesteros P

    更新日期:2003-12-01 00:00:00

  • Cholinesterase inhibitors: SAR and enzyme inhibitory activity of 3-[omega-(benzylmethylamino)alkoxy]xanthen-9-ones.

    abstract::In this work, we further investigated a previously introduced class of cholinesterase inhibitors. The removal of the carbamic function from the lead compound xanthostigmine led to a reversible cholinesterase inhibitors 3. Some new 3-[omega-(benzylmethylamino)alkoxy]xanthen-9-one analogs were designed, synthesized, and...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Piazzi L,Belluti F,Bisi A,Gobbi S,Rizzo S,Bartolini M,Andrisano V,Recanatini M,Rampa A

    更新日期:2007-01-01 00:00:00

  • Equol, a natural estrogenic metabolite from soy isoflavones: convenient preparation and resolution of R- and S-equols and their differing binding and biological activity through estrogen receptors alpha and beta.

    abstract::Equol is a metabolite produced in vivo from the soy phytoestrogen daidzein by the action of gut microflora. It is known to be estrogenic, so human exposure to equol could have significant biological effects. Equol is a chiral molecule that can exist as the enantiomers R-equol and S-equol. To study the biological activ...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Muthyala RS,Ju YH,Sheng S,Williams LD,Doerge DR,Katzenellenbogen BS,Helferich WG,Katzenellenbogen JA

    更新日期:2004-03-15 00:00:00

  • Antiplasmodial activity of targeted zinc(II)-dipicolylamine complexes.

    abstract::This study measured the antiplasmodial activity of nine zinc-dipicolylamine (ZnDPA) complexes against three strains of Plasmodium falciparum, the causative parasite of malaria. Growth inhibition assays showed significant activity against all tested strains, with 50% inhibitory concentrations between 5 and 600nM and al...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Rice DR,de Lourdes Betancourt Mendiola M,Murillo-Solano C,Checkley LA,Ferdig MT,Pizarro JC,Smith BD

    更新日期:2017-05-15 00:00:00

  • Cyclic MOG35-55 ameliorates clinical and neuropathological features of experimental autoimmune encephalomyelitis.

    abstract::EAE is induced to susceptible mice using linear peptides of myelin proteins of the central nervous system. Specific peptide motifs within the peptide-binding groove of the MHC peptide-complex determines the affinity of the peptide in each animal and the consequent T-cell receptor recognition and activation of the cell...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Lourbopoulos A,Deraos G,Matsoukas MT,Touloumi O,Giannakopoulou A,Kalbacher H,Grigoriadis N,Apostolopoulos V,Matsoukas J

    更新日期:2017-08-01 00:00:00

  • Design, synthesis and biological evaluation of 2-phenylquinoline-4-carboxamide derivatives as a new class of tubulin polymerization inhibitors.

    abstract::A novel series of 2-phenylquinoline-4-carboxamide derivatives was synthesized, characterized and evaluated for its antiproliferative activity against five cancer cell lines, Hela, SK-OV-3, HCT116, A549 and MDA-MB-468, and a normal human fetal lung fibroblastic cell line, MRC-5. Among them, compound 7b displayed potent...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Zhu L,Luo K,Li K,Jin Y,Lin J

    更新日期:2017-11-01 00:00:00

  • Semisynthesis of DB-67 and other silatecans from camptothecin by thiol-promoted addition of silyl radicals.

    abstract::Thiol- or acid-promoted additions of silyl radicals to camptothecin are reported. At 105 degrees C, mixtures of 7-silyl (favored) and 12-silyl camptothecins are formed alongside substantial amounts of recovered camptothecin. At 160 degrees C, 12-silyl isomers are formed preferentially, but the total mass balance is su...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Du W,Kaskar B,Blumbergs P,Subramanian PK,Curran DP

    更新日期:2003-02-06 00:00:00

  • Design, synthesis and QSAR studies on N-aryl heteroarylisopropanolamines, a new class of non-peptidic HIV-1 protease inhibitors.

    abstract::A series of N-aryl heteroarylisopropanolamines in which an indole or a 3-arylpyrrole moiety was linked to an aryl group through an isopropanolamine linker, were designed and synthesized as potential anti-HIV-1-PR agents. Series was tested for their ability in blocking PR activity. As a rule, indole derivatives of clas...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Di Santo R,Costi R,Artico M,Massa S,Ragno R,Marshall GR,La Colla P

    更新日期:2002-08-01 00:00:00

  • Solution-phase parallel synthesis of substituted chalcones and their antiparasitary activity against Giardia lamblia.

    abstract::A library of 25-membered chalcones was prepared by parallel synthesis. Substituted acetophenones and benzaldehydes were condensed using the Claisen-Schmidt base-catalyzed aldol condensation. Several chalcones showed in vitro antiparasitic activity against Giardia lamblia. The highest activity observed for the IC(50) v...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Montes-Avila J,Díaz-Camacho SP,Sicairos-Félix J,Delgado-Vargas F,Rivero IA

    更新日期:2009-09-15 00:00:00

  • Design and synthesis of de novo cytotoxic alkaloids by mimicking the bioactive conformation of paclitaxel.

    abstract::Novel paclitaxel-mimicking alkaloids were designed and synthesized based on a bioactive conformation of paclitaxel, that is, REDOR-Taxol. The alkaloid 2 bearing a 5-7-6 tricyclic scaffold mimics REDOR-Taxol best among the compounds designed and was found to be the most potent compound against several drug-sensitive an...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Sun L,Veith JM,Pera P,Bernacki RJ,Ojima I

    更新日期:2010-10-01 00:00:00

  • N-substituted aminohydroxypyridines as potential non-opioid analgesic agents.

    abstract::A series of new N-substituted aminohydroxypyridines have been synthesized, pharmacologically evaluated and compared with their N-substituted oxazolopyridone analogs. The compound with the maximal combination of safety and analgesic efficacy was 3-[2-[4-(4-fluorophenyl)-1-piperazinyl]ethyl]amino-2-hydroxypyridine (comp...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Viaud MC,Jamoneau P,Bizot-Espiard JG,Pfeiffer B,Renard P,Caignard DH,Adam G,Guillaumet G

    更新日期:1995-07-01 00:00:00

  • Screening, synthesis, crystal structure, and molecular basis of 6-amino-4-phenyl-1,4-dihydropyrano[2,3-c]pyrazole-5-carbonitriles as novel AKR1C3 inhibitors.

    abstract::AKR1C3 is a promising therapeutic target for castration-resistant prostate cancer. Herein, an evaluation of in-house library discovered substituted pyranopyrazole as a novel scaffold for AKR1C3 inhibitors. Preliminary SAR exploration identified its derivative 19d as the most promising compound with an IC50 of 0.160 μM...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Zheng X,Jiang Z,Li X,Zhang C,Li Z,Wu Y,Wang X,Zhang C,Luo HB,Xu J,Wu D

    更新日期:2018-12-01 00:00:00

  • Synthesis and proteasome inhibition of glycyrrhetinic acid derivatives.

    abstract::This study discovered that glycyrrhetinic acid inhibited the human 20S proteasome at 22.3microM. Esterification of the C-3 hydroxyl group on glycyrrhetinic acid with various carboxylic acid reagents yielded a series of analogs with marked improved potency. Among the derivatives, glycyrrhetinic acid 3-O-isophthalate (1...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Huang L,Yu D,Ho P,Qian K,Lee KH,Chen CH

    更新日期:2008-07-15 00:00:00

  • Targeting the Warburg Effect in cancer; relationships for 2-arylpyridazinones as inhibitors of the key glycolytic enzyme 6-phosphofructo-2-kinase/2,6-bisphosphatase 3 (PFKFB3).

    abstract::High-throughput screening of a small-molecule library identified a 5-triazolo-2-arylpyridazinone as a novel inhibitor of the important glycolytic enzyme 6-phosphofructo-2-kinase/2,6-bisphosphatase 3 (PFKFB3). Such inhibitors are of interest due to PFKFB3's control of the important glycolytic pathway used by cancer cel...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Brooke DG,van Dam EM,Watts CK,Khoury A,Dziadek MA,Brooks H,Graham LJ,Flanagan JU,Denny WA

    更新日期:2014-02-01 00:00:00

  • Novel 6-hydroxy-3-morpholinones as cornea permeable calpain inhibitors.

    abstract::A novel series of 6-hydroxy-3-morpholinones, in which the functional aldehyde and the hydroxy group of P(2) site form a cyclic hemiacetal, was identified as calpain inhibitors. The placement of isobutyl group at the 2-position of the 3-morpholinone was the most effective modification for inhibiting micro- and m-calpai...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Nakamura M,Miyashita H,Yamaguchi M,Shirasaki Y,Nakamura Y,Inoue J

    更新日期:2003-12-01 00:00:00

  • Biodistribution of (125)I-labeled polymeric vaccine carriers after subcutaneous injection.

    abstract::Polymeric nanoparticles (NPs) comprised of hydrophilic poly(γ-glutamic acid) in the main chain and hydrophobic phenylalanine in the side chain (γ-PGA-Phe) are a promising vaccine carrier for various kinds of diseases. However, little is known about the fate of subcutaneously administered γ-PGA-Phe NPs. Therefore, we n...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Toita R,Kanai Y,Watabe H,Nakao K,Yamamoto S,Hatazawa J,Akashi M

    更新日期:2013-09-01 00:00:00

  • Isolation and characterization of a monoamine oxidase B selective inhibitor from tobacco smoke.

    abstract::It is well established that tobacco smokers have reduced levels of monoamine oxidase activities both in the brain and peripheral organs. Furthermore, extensive evidence suggests that smokers are less prone to develop Parkinson's disease. These facts, plus the observation that inhibition of monoamine oxidase B protects...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Khalil AA,Davies B,Castagnoli N Jr

    更新日期:2006-05-15 00:00:00

  • Synthesis and antimalarial evaluation of a screening library based on a tetrahydroanthraquinone natural product scaffold.

    abstract::As part of a research program aimed at discovering new antimalarial leads from Australian macrofungi a unique fungi-derived prefractionated library was screened against a chloroquine-sensitive Plasmodium falciparum line (3D7) using a radiometric growth inhibition assay. A library fraction derived from a Cortinarius sp...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Choomuenwai V,Andrews KT,Davis RA

    更新日期:2012-12-15 00:00:00

  • YM-254890 analogues, novel cyclic depsipeptides with Galpha(q/11) inhibitory activity from Chromobacterium sp. QS3666.

    abstract::The structure elucidation and biological activity of novel YM-254890 (1) analogues and semi-synthetic derivatives are described. Three natural analogues, YM-254891 (2), YM-254892 (3), and YM-280193 (4), were isolated from the fermentation broth of Chromobacterium sp. QS3666, and two hydrogenated derivatives, YM-385780...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Taniguchi M,Suzumura K,Nagai K,Kawasaki T,Takasaki J,Sekiguchi M,Moritani Y,Saito T,Hayashi K,Fujita S,Tsukamoto S,Suzuki K

    更新日期:2004-06-15 00:00:00

  • Effects of detergents on the West Nile virus protease activity.

    abstract::Detergents such as Triton X-100 are often used in drug discovery research to weed out small molecule promiscuous and non-specific inhibitors which act by aggregation in solution and undesirable precipitation in aqueous assay buffers. We evaluated the effects of commonly used detergents, Triton X-100, Tween-20, Nonidet...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Ezgimen MD,Mueller NH,Teramoto T,Padmanabhan R

    更新日期:2009-05-01 00:00:00

  • Optimization and bioevaluation of Cdc37-derived peptides: An insight into Hsp90-Cdc37 protein-protein interaction modulators.

    abstract::Targeting Hsp90-Cdc37 protein-protein interaction (PPI) is becoming an alternative approach for future anti-cancer drug development. We previously reported the discovery of an eleven-residue peptide (Pep-1) with micromolar activity for the disruption of Hsp90-Cdc37 PPI. Efforts to improve upon the Pep-1 led to the dis...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Wang L,Li L,Fu WT,Jiang ZY,You QD,Xu XL

    更新日期:2017-01-01 00:00:00

  • Estimation of hERG inhibition of drug candidates using multivariate property and pharmacophore SAR.

    abstract::We describe the development of a computational model for the prediction of the inhibition of K(+) flow through the hERG ion channel. Using a collection of 1075 discovery compounds with hERG inhibition measured in our standard patch-clamp electrophysiology assay, molecular features important for drug-induced inhibition...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Johnson SR,Yue H,Conder ML,Shi H,Doweyko AM,Lloyd J,Levesque P

    更新日期:2007-09-15 00:00:00

  • Synthesis of chlorogenic acid derivatives with promising antifungal activity.

    abstract::Derivatives of chlorogenic acid or its analogues were synthesized by coupling protected chlorogenic acid or its analogues with p-octyloxyaniline and selected amino acids. Most of the compounds exhibited significant potency against Cryptococcus neoformans and Candida species with low toxicity to brine shrimps. The 4,5-...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Ma CM,Kully M,Khan JK,Hattori M,Daneshtalab M

    更新日期:2007-11-01 00:00:00

  • Novel inhibitors targeting PPM1D phosphatase potently suppress cancer cell proliferation.

    abstract::Protein phosphatase magnesium-dependent 1δ (PPM1D, Wip1) is a p53 inducible serine/threonine phosphatase. PPM1D is a promising target protein in cancer therapy since overexpression, missense mutations, truncating mutations, and gene amplification of PPM1D are reported in many tumors, including breast cancer and neurob...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Ogasawara S,Kiyota Y,Chuman Y,Kowata A,Yoshimura F,Tanino K,Kamada R,Sakaguchi K

    更新日期:2015-10-01 00:00:00

  • Chemistry-driven glycoscience.

    abstract::Carbohydrates are the most prominent features of the cell's exterior-they are the cell's "face" and serve as the cell's identification card. The features of cell surface glycans (e.g. glycoproteins, glycolipids, polysaccharides) can be read by proteins, other cells, or organisms. In all of these contexts, glycan-bindi...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 社论


    authors: Kiessling LL

    更新日期:2018-10-15 00:00:00

  • Molecular design of anti-MRSA agents based on the anacardic acid scaffold.

    abstract::A series of anacardic acid analogues possessing different side chains viz. phenolic, branched, and alicyclic were synthesized and their antibacterial activity tested against methicillin-resistant Staphylococcus aureus (MRSA). The maximum activity against this bacterium occurred with the branched side-chain analogue, 6...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Green IR,Tocoli FE,Lee SH,Nihei K,Kubo I

    更新日期:2007-09-15 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


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

    更新日期:2010-01-15 00:00:00