当前位置： SCI文献检索 > Journal of Chemical Information and Modeling期刊下所有文献 > Structure-Based Rational Design of Novel Inhibitors Against Fructose-1,6-Bisphosphate Aldolase from Candida albicans.

Structure-Based Rational Design of Novel Inhibitors Against Fructose-1,6-Bisphosphate Aldolase from Candida albicans.

Abstract：

:Class II fructose-1,6-bisphosphate aldolases (FBA-II) are attractive new targets for the discovery of drugs to combat invasive fungal infection, because they are absent in animals and higher plants. Although several FBA-II inhibitors have been reported, none of these inhibitors exhibit antifungal effect so far. In this study, several novel inhibitors of FBA-II from C. albicans (Ca-FBA-II) with potent antifungal effects were rationally designed by jointly using a specific protocols of molecular docking-based virtual screening, accurate binding-conformation evaluation strategy, synthesis and enzymatic assays. The enzymatic assays reveal that the compounds 3c, 3e-g, 3j and 3k exhibit high inhibitory activity against Ca-FBA-II (IC50 < 10 μM), and the most potential inhibitor is 3g, with IC50 value of 2.7 μM. Importantly, the compounds 3f, 3g, and 3l possess not only high inhibitions against Ca-FBA-II, but also moderate antifungal activities against C. glabrata (MIC80 = 4-64 μg/mL). The compounds 3g, 3l, and 3k in combination with fluconazole (8 μg/mL) displayed significantly synergistic antifungal activities (MIC80 < 0.0625 μg/mL) against resistant Candida strains, which are resistant to azoles drugs. The probable binding modes between 3g and the active site of Ca-FBA-II have been proposed by using the DOX (docking, ONIOM, and XO) strategy. To our knowledge, no FBA-II inhibitors with antifungal activities against wild type and resistant strains from Candida were reported previously. The positive results suggest that the strategy adopted in this study are a promising method for the discovery of novel drugs against azole-resistant fungal pathogens in the future.

journal_name

J Chem Inf Model

journal_title

Journal of chemical information and modeling

authors

Han X,Zhu X,Hong Z,Wei L,Ren Y,Wan F,Zhu S,Peng H,Guo L,Rao L,Feng L,Wan J

doi

10.1021/acs.jcim.6b00763

subject

Has Abstract

pub_date

2017-06-26 00:00:00

pages

1426-1438

issue

6

eissn

1549-9596

issn

1549-960X

journal_volume

57

pub_type

杂志文章

相关文献

Journal of Chemical Information and Modeling文献大全
  • Radial clustergrams: visualizing the aggregate properties of hierarchical clusters.

    abstract：:A new radial space-filling method for visualizing cluster hierarchies is presented. The method, referred to as a radial clustergram, arranges the clusters into a series of layers, each representing a different level of the tree. It uses adjacency of nodes instead of links to represent parent-child relationships and al...

    journal_title：Journal of chemical information and modeling

    pub_type： 杂志文章

    doi：10.1021/ci600427x

    authors： Agrafiotis DK,Bandyopadhyay D,Farnum M

    更新日期：2007-01-01 00:00:00

  • Molecular Mechanism underlying PRMT1 Dimerization for SAM Binding and Methylase Activity.

    abstract：:Protein arginine methyltransferases (PRMTs) catalyze the posttranslational methylation of arginine, which is important in a range of biological processes, including epigenetic regulation, signal transduction, and cancer progression. Although previous studies of PRMT1 mutants suggest that the dimerization arm and the N...

    journal_title：Journal of chemical information and modeling

    pub_type： 杂志文章

    doi：10.1021/acs.jcim.5b00454

    authors： Zhou R,Xie Y,Hu H,Hu G,Patel VS,Zhang J,Yu K,Huang Y,Jiang H,Liang Z,Zheng YG,Luo C

    更新日期：2015-12-28 00:00:00

  • Factors affecting d-block metal-ligand bond lengths: toward an automated library of molecular geometry for metal complexes.

    abstract：:Metal-ligand (M-L) bond lengths for a range of ligands (carboxylates, chlorides, pyridines, water, tertiary phosphines, and alkenes) and a variety of metals have been retrieved from the Cambridge Structural Database, CSD. Analysis of the factors which affect M-L bond lengths (for example, ligand coordination mode, oxi...

    journal_title：Journal of chemical information and modeling

    pub_type： 杂志文章

    doi：10.1021/ci0500785

    authors： Harris SE,Orpen AG,Bruno IJ,Taylor R

    更新日期：2005-11-01 00:00:00

  • An Analysis of Different Components of a High-Throughput Screening Library.

    abstract：:Since many projects at pharmaceutical organizations get their start from a high-throughput screening (HTS) campaign, improving the quality of the HTS deck can improve the likelihood of discovering a high-quality lead molecule that can be progressed to a drug candidate. Over the past decade, Janssen has implemented sev...

    journal_title：Journal of chemical information and modeling

    pub_type： 杂志文章

    doi：10.1021/acs.jcim.8b00258

    authors： Saha A,Varghese T,Liu A,Allen SJ,Mirzadegan T,Hack MD

    更新日期：2018-10-22 00:00:00

  • Linear and nonlinear 3D-QSAR approaches in tandem with ligand-based homology modeling as a computational strategy to depict the pyrazolo-triazolo-pyrimidine antagonists binding site of the human adenosine A2A receptor.

    abstract：:The integration of ligand- and structure-based strategies might sensitively increase the success of drug discovery process. We have recently described the application of Molecular Electrostatic Potential autocorrelated vectors (autoMEPs) in generating both linear (Partial Least-Square, PLS) and nonlinear (Response Sur...

    journal_title：Journal of chemical information and modeling

    pub_type： 杂志文章

    doi：10.1021/ci700300w

    authors： Michielan L,Bacilieri M,Schiesaro A,Bolcato C,Pastorin G,Spalluto G,Cacciari B,Klotz KN,Kaseda C,Moro S

    更新日期：2008-02-01 00:00:00

  • ChemSchematicResolver: A Toolkit to Decode 2D Chemical Diagrams with Labels and R-Groups into Annotated Chemical Named Entities.

    abstract：:The number of journal articles in the scientific domain has grown to the point where it has become impossible for researchers to capitalize on all findings in their relevant discipline. Information is stored in these articles in a number of ways, including figures that describe important results. In organic chemistry,...

    journal_title：Journal of chemical information and modeling

    pub_type： 杂志文章

    doi：10.1021/acs.jcim.0c00042

    authors： Beard EJ,Cole JM

    更新日期：2020-04-27 00:00:00

  • Comparison of several molecular docking programs: pose prediction and virtual screening accuracy.

    abstract：:Molecular docking programs are widely used modeling tools for predicting ligand binding modes and structure based virtual screening. In this study, six molecular docking programs (DOCK, FlexX, GLIDE, ICM, PhDOCK, and Surflex) were evaluated using metrics intended to assess docking pose and virtual screening accuracy. ...

    journal_title：Journal of chemical information and modeling

    pub_type： 杂志文章

    doi：10.1021/ci900056c

    authors： Cross JB,Thompson DC,Rai BK,Baber JC,Fan KY,Hu Y,Humblet C

    更新日期：2009-06-01 00:00:00

  • Evaluation and Characterization of Trk Kinase Inhibitors for the Treatment of Pain: Reliable Binding Affinity Predictions from Theory and Computation.

    abstract：:Optimization of ligand binding affinity to the target protein of interest is a primary objective in small-molecule drug discovery. Until now, the prediction of binding affinities by computational methods has not been widely applied in the drug discovery process, mainly because of its lack of accuracy and reproducibili...

    journal_title：Journal of chemical information and modeling

    pub_type： 杂志文章

    doi：10.1021/acs.jcim.6b00780

    authors： Wan S,Bhati AP,Skerratt S,Omoto K,Shanmugasundaram V,Bagal SK,Coveney PV

    更新日期：2017-04-24 00:00:00

  • Mesoscopic simulation of phospholipid membranes, peptides, and proteins with molecular fragment dynamics.

    abstract：:Molecular fragment dynamics (MFD) is a variant of dissipative particle dynamics (DPD), a coarse-grained mesoscopic simulation technique for isothermal complex fuids and soft matter systems with particles that are chosen to be adequate fluid elements. MFD choses its particles to be small molecules which may be connecte...

    journal_title：Journal of chemical information and modeling

    pub_type： 杂志文章

    doi：10.1021/ci5006096

    authors： Truszkowski A,van den Broek K,Kuhn H,Zielesny A,Epple M

    更新日期：2015-05-26 00:00:00

  • Criterion for evaluating the predictive ability of nonlinear regression models without cross-validation.

    abstract：:We propose predictive performance criteria for nonlinear regression models without cross-validation. The proposed criteria are the determination coefficient and the root-mean-square error for the midpoints between k-nearest-neighbor data points. These criteria can be used to evaluate predictive ability after the regre...

    journal_title：Journal of chemical information and modeling

    pub_type： 杂志文章

    doi：10.1021/ci4003766

    authors： Kaneko H,Funatsu K

    更新日期：2013-09-23 00:00:00

  • Rotational Profiler: A Fast, Automated, and Interactive Server to Derive Torsional Dihedral Potentials for Classical Molecular Simulations.

    abstract：:Rotational Profiler provides an analytical algorithm to compute sets of classical torsional dihedral parameters by fitting an empirical energy profile to a reference one that can be obtained experimentally or by quantum-mechanical methods. The resulting profiles are compatible with the functional forms in the most wid...

    journal_title：Journal of chemical information and modeling

    pub_type： 杂志文章

    doi：10.1021/acs.jcim.0c01168

    authors： Rusu VH,Santos DES,Poleto MD,Galheigo MM,Gomes ATA,Verli H,Soares TA,Lins RD

    更新日期：2020-12-28 00:00:00

  • Locating sweet spots for screening hits and evaluating pan-assay interference filters from the performance analysis of two lead-like libraries.

    abstract：:The efficiency of automated compound screening is heavily influenced by the design and the quality of the screening libraries used. We recently reported on the assembly of one diverse and one target-focused lead-like screening library. Using data from 15 enzyme-based screenings conducted using these libraries, their p...

    journal_title：Journal of chemical information and modeling

    pub_type： 杂志文章

    doi：10.1021/ci300382f

    authors： Mok NY,Maxe S,Brenk R

    更新日期：2013-03-25 00:00:00

  • Exploring Tunable Hyperparameters for Deep Neural Networks with Industrial ADME Data Sets.

    abstract：:Deep learning has drawn significant attention in different areas including drug discovery. It has been proposed that it could outperform other machine learning algorithms, especially with big data sets. In the field of pharmaceutical industry, machine learning models are built to understand quantitative structure-acti...

    journal_title：Journal of chemical information and modeling

    pub_type： 杂志文章

    doi：10.1021/acs.jcim.8b00671

    authors： Zhou Y,Cahya S,Combs SA,Nicolaou CA,Wang J,Desai PV,Shen J

    更新日期：2019-03-25 00:00:00

  • CoMFA, CoMSIA, and molecular hologram QSAR studies of novel neuronal nAChRs ligands-open ring analogues of 3-pyridyl ether.

    abstract：:3-Pyridyl ethers are excellent nAChRs ligands, which show high subtype selectivity and binding affinity to alpha4beta2 nAChR. Although the quantitative structure-activity relationship (QSAR) of nAChRs ligands has been widely investigated using various classes of compounds, the open ring analogues of 3-pyridyl ethers h...

    journal_title：Journal of chemical information and modeling

    pub_type： 杂志文章

    doi：10.1021/ci0498113

    authors： Zhang H,Li H,Liu C

    更新日期：2005-03-01 00:00:00

  • In silico analysis of the thermodynamic stability changes of psychrophilic and mesophilic alpha-amylases upon exhaustive single-site mutations.

    abstract：:Identifying sequence modifications that distinguish psychrophilic from mesophilic proteins is important for designing enzymes with different thermodynamic stabilities and to understand the underlying mechanisms. The PoPMuSiC algorithm is used to introduce, in silico, all the single-site mutations in four mesophilic an...

    journal_title：Journal of chemical information and modeling

    pub_type： 杂志文章

    doi：10.1021/ci050473v

    authors： Gilis D

    更新日期：2006-05-01 00:00:00

  • Relationships between Molecular Complexity, Biological Activity, and Structural Diversity.

    abstract：:Following the theoretical model by Hann et al. moderately complex structures are preferable lead compounds since they lead to specific binding events involving the complete ligand molecule. To make this concept usable in practice for library design, we studied several complexity measures on the biological activity of ...

    journal_title：Journal of chemical information and modeling

    pub_type： 杂志文章

    doi：10.1021/ci0503558

    authors： Schuffenhauer A,Brown N,Selzer P,Ertl P,Jacoby E

    更新日期：2006-03-01 00:00:00

  • Combined 3D-QSAR modeling and molecular docking study on indolinone derivatives as inhibitors of 3-phosphoinositide-dependent protein kinase-1.

    abstract：:3-Phosphoinositide-dependent protein kinase-1 (PDK1) is a promising target for developing novel anticancer drugs. In order to understand the structure-activity correlation of indolinone-based PDK1 inhibitors, we have carried out a combined molecular docking and three-dimensional quantitative structure-activity relatio...

    journal_title：Journal of chemical information and modeling

    pub_type： 杂志文章

    doi：10.1021/ci800147v

    authors： AbdulHameed MD,Hamza A,Liu J,Zhan CG

    更新日期：2008-09-01 00:00:00

  • Comparative Assessment of Scoring Functions: The CASF-2016 Update.

    abstract：:In structure-based drug design, scoring functions are often employed to evaluate protein-ligand interactions. A variety of scoring functions have been developed so far, and thus, some objective benchmarks are desired for assessing their strength and weakness. The comparative assessment of scoring functions (CASF) benc...

    journal_title：Journal of chemical information and modeling

    pub_type： 杂志文章

    doi：10.1021/acs.jcim.8b00545

    authors： Su M,Yang Q,Du Y,Feng G,Liu Z,Li Y,Wang R

    更新日期：2019-02-25 00:00:00

  • Substituted 4,5'-Bithiazoles as Catalytic Inhibitors of Human DNA Topoisomerase IIα.

    abstract：:Human type II topoisomerases, molecular motors that alter the DNA topology, are a major target of modern chemotherapy. Groups of catalytic inhibitors represent a new approach to overcome the known limitations of topoisomerase II poisons such as cardiotoxicity and induction of secondary tumors. Here, we present a class...

    journal_title：Journal of chemical information and modeling

    pub_type： 杂志文章

    doi：10.1021/acs.jcim.0c00202

    authors： Bergant Loboda K,Janežič M,Štampar M,Žegura B,Filipič M,Perdih A

    更新日期：2020-07-27 00:00:00

  • Predictive models for cytochrome p450 isozymes based on quantitative high throughput screening data.

    abstract：:The human cytochrome P450 (CYP450) isozymes are the most important enzymes in the body to metabolize many endogenous and exogenous substances including environmental toxins and therapeutic drugs. Any unnecessary interactions between a small molecule and CYP450 isozymes may raise a potential to disarm the integrity of ...

    journal_title：Journal of chemical information and modeling

    pub_type： 杂志文章

    doi：10.1021/ci200311w

    authors： Sun H,Veith H,Xia M,Austin CP,Huang R

    更新日期：2011-10-24 00:00:00

  • Support vector regression scoring of receptor-ligand complexes for rank-ordering and virtual screening of chemical libraries.

    abstract：:The community structure-activity resource (CSAR) data sets are used to develop and test a support vector machine-based scoring function in regression mode (SVR). Two scoring functions (SVR-KB and SVR-EP) are derived with the objective of reproducing the trend of the experimental binding affinities provided within the ...

    journal_title：Journal of chemical information and modeling

    pub_type： 杂志文章

    doi：10.1021/ci200078f

    authors： Li L,Wang B,Meroueh SO

    更新日期：2011-09-26 00:00:00

  • Predicted Biological Activity of Purchasable Chemical Space.

    abstract：:Whereas 400 million distinct compounds are now purchasable within the span of a few weeks, the biological activities of most are unknown. To facilitate access to new chemistry for biology, we have combined the Similarity Ensemble Approach (SEA) with the maximum Tanimoto similarity to the nearest bioactive to predict a...

    journal_title：Journal of chemical information and modeling

    pub_type： 杂志文章

    doi：10.1021/acs.jcim.7b00316

    authors： Irwin JJ,Gaskins G,Sterling T,Mysinger MM,Keiser MJ

    更新日期：2018-01-22 00:00:00

  • Probing the Binding Pathway of BRACO19 to a Parallel-Stranded Human Telomeric G-Quadruplex Using Molecular Dynamics Binding Simulation with AMBER DNA OL15 and Ligand GAFF2 Force Fields.

    abstract：:Human telomeric DNA G-quadruplex has been identified as a good therapeutic target in cancer treatment. G-quadruplex-specific ligands that stabilize the G-quadruplex have great potential to be developed as anticancer agents. Two crystal structures (an apo form of parallel stranded human telomeric G-quadruplex and its h...

    journal_title：Journal of chemical information and modeling

    pub_type： 杂志文章

    doi：10.1021/acs.jcim.7b00287

    authors： Machireddy B,Kalra G,Jonnalagadda S,Ramanujachary K,Wu C

    更新日期：2017-11-27 00:00:00

  • Binding Interactions of Ergotamine and Dihydroergotamine to 5-Hydroxytryptamine Receptor 1B (5-HT1b) Using Molecular Dynamics Simulations and Dynamic Network Analysis.

    abstract：:Ergotamine (ERG) and dihydroergotamine (DHE), common migraine drugs, have small structural differences but lead to clinically important distinctions in their pharmacological profiles. For example, DHE is less potent than ERG by about 10-fold at the 5-hydroxytrptamine receptor 1B (5-HT1B). Although the high-resolution ...

    journal_title：Journal of chemical information and modeling

    pub_type： 杂志文章

    doi：10.1021/acs.jcim.9b01082

    authors： Sullivan HJ,Tursi A,Moore K,Campbell A,Floyd C,Wu C

    更新日期：2020-03-23 00:00:00

  • VMD Store-A VMD Plugin to Browse, Discover, and Install VMD Extensions.

    abstract：:Herein we present the VMD Store, an open-source VMD plugin that simplifies the way that users browse, discover, install, update, and uninstall extensions for the Visual Molecular Dynamics (VMD) software. The VMD Store obtains data about all the indexed VMD extensions hosted on GitHub and presents a one-click mechanism...

    journal_title：Journal of chemical information and modeling

    pub_type： 杂志文章

    doi：10.1021/acs.jcim.9b00739

    authors： Fernandes HS,Sousa SF,Cerqueira NMFSA

    更新日期：2019-11-25 00:00:00

  • Exploring Topological Pharmacophore Graphs for Scaffold Hopping.

    abstract：:The primary goal of ligand-based virtual screening is to identify active compounds consisting of a core scaffold that is not found in the current active compound pool. Scaffold hopping is the term used for this purpose. In the present study, topological representations of pharmacophore features on chemical graphs were...

    journal_title：Journal of chemical information and modeling

    pub_type： 杂志文章

    doi：10.1021/acs.jcim.0c00098

    authors： Nakano H,Miyao T,Funatsu K

    更新日期：2020-04-27 00:00:00

  • In silico deconstruction of ATP-competitive inhibitors of glycogen synthase kinase-3β.

    abstract：:Fragment-based methods have emerged in the last two decades as alternatives to traditional high throughput screenings for the identification of chemical starting points in drug discovery. One arguable yet popular assumption about fragment-based design is that the fragment binding mode remains conserved upon chemical e...

    journal_title：Journal of chemical information and modeling

    pub_type： 杂志文章

    doi：10.1021/ci300355p

    authors： Bisignano P,Lambruschini C,Bicego M,Murino V,Favia AD,Cavalli A

    更新日期：2012-12-21 00:00:00

  • PIIMS Server: A Web Server for Mutation Hotspot Scanning at the Protein-Protein Interface.

    abstract：:Protein-protein interactions (PPIs) play vital roles in regulating biological processes, such as cellular and signaling pathways. Hotspots are certain residues located at protein-protein interfaces that contribute more in protein-protein binding than other residues. Research on the mutational effects of hotspots is im...

    journal_title：Journal of chemical information and modeling

    pub_type： 杂志文章

    doi：10.1021/acs.jcim.0c00966

    authors： Wu FX,Yang JF,Mei LC,Wang F,Hao GF,Yang GF

    更新日期：2021-01-25 00:00:00

  • Pharmacophore-based virtual screening and experimental validation of novel inhibitors against cyanobacterial fructose-1,6-/sedoheptulose-1,7-bisphosphatase.

    abstract：:Cyanobacterial fructose-1,6-/sedoheptulose-1,7-bisphoshatase (cy-FBP/SBPase) is a potential enzymatic target for screening of novel inhibitors that can combat harmful algal blooms. In the present study, we targeted the substrate binding pocket of cy-FBP/SBPase. A series of novel hit compounds from the SPECs database w...

    journal_title：Journal of chemical information and modeling

    pub_type： 杂志文章

    doi：10.1021/ci4007529

    authors： Sun Y,Zhang R,Li D,Feng L,Wu D,Feng L,Huang P,Ren Y,Feng J,Xiao S,Wan J

    更新日期：2014-03-24 00:00:00

  • Metabotropic glutamate receptor-mediated currents at the climbing fiber to Purkinje cell synapse.

    abstract：:Different forms of synaptic plasticity in the cerebellum expressed at the synapses onto Purkinje cells (PCs) are mediated by membrane metabotropic glutamate receptors (mGluRs). There are three main mGluR groups with a total of 8 subtypes. Although mGluRs are also found at the climbing fiber (CF) to PC synapses, the di...

    journal_title：Journal of chemical information and modeling

    pub_type： 杂志文章

    doi：10.1021/ci050161s

    authors： Andjus PR,Bajić A,Zhu L,Strata P

    更新日期：2005-11-01 00:00:00