Novel inhibitors of trihydroxynaphthalene reductase with antifungal activity identified by ligand-based and structure-based virtual screening.

Abstract:

:Curvularia lunata is a dark pigmented fungus that is the causative agent of several diseases in plants and in both immunodeficient and immunocompetent patients. 1,8-Dihydroxynaphthalene-melanin is found in the cell wall of C. lunata and is believed to be the important virulence factor of dematiaceous fungi. Trihydroxynaphthalene reductase is an enzyme of the 1,8-dihydroxynaphthalene-melanin biosynthetic pathway, and it thus represents an emerging target for the development of novel fungicides and antimycotics. In the present study, we describe novel inhibitors of trihydroxynaphthalene reductase from C. lunata. These inhibitors were identified by ligand-based three-dimensional similarity searching and docking to a homology-built model and by subsequent biochemical and antifungal evaluation. Discovery of competitive inhibitors with K(i) values in low micromolar and even nanomolar concentration range proves the aplicability of homology-built model of 3HNR for hit finding by virtual screening methods.

journal_name

J Chem Inf Model

authors

Brunskole Svegelj M,Turk S,Brus B,Lanisnik Rizner T,Stojan J,Gobec S

doi

10.1021/ci2001499

subject

Has Abstract

pub_date

2011-07-25 00:00:00

pages

1716-24

issue

7

eissn

1549-9596

issn

1549-960X

journal_volume

51

pub_type

杂志文章
  • SERAPhiC: a benchmark for in silico fragment-based drug design.

    abstract::Our main objective was to compile a data set of high-quality protein-fragment complexes and make it publicly available. Once assembled, the data set was challenged using docking procedures to address the following questions: (i) Can molecular docking correctly reproduce the experimentally solved structures? (ii) How t...

    journal_title:Journal of chemical information and modeling

    pub_type: 杂志文章

    doi:10.1021/ci2003363

    authors: Favia AD,Bottegoni G,Nobeli I,Bisignano P,Cavalli A

    更新日期:2011-11-28 00:00:00

  • Benchmark Sets for Binding Hot Spot Identification in Fragment-Based Ligand Discovery.

    abstract::Binding hot spots are regions of proteins that, due to their potentially high contribution to the binding free energy, have high propensity to bind small molecules. We present benchmark sets for testing computational methods for the identification of binding hot spots with emphasis on fragment-based ligand discovery. ...

    journal_title:Journal of chemical information and modeling

    pub_type: 杂志文章

    doi:10.1021/acs.jcim.0c00877

    authors: Wakefield AE,Yueh C,Beglov D,Castilho MS,Kozakov D,Keserű GM,Whitty A,Vajda S

    更新日期:2020-12-28 00:00:00

  • L-arginine binding to human inducible nitric oxide synthase: an antisymmetric funnel route toward isoform-specific inhibitors?

    abstract::Nitric oxide (NO) is an important signaling molecule produced by a family of enzymes called nitric oxide synthases (NOS). Because NO is involved in various pathological conditions, the development of potent and isoform-selective NOS inhibitors is an important challenge. In the present study, the dimer of oxygenase dom...

    journal_title:Journal of chemical information and modeling

    pub_type: 杂志文章

    doi:10.1021/ci100422v

    authors: Floquet N,Hernandez JF,Boucher JL,Martinez J

    更新日期:2011-06-27 00:00:00

  • Bridging molecular docking to membrane molecular dynamics to investigate GPCR-ligand recognition: the human A₂A adenosine receptor as a key study.

    abstract::G protein-coupled receptors (GPCRs) represent the largest family of cell-surface receptors and about one-third of the actual targets of clinically used drugs. Following the progress made in the field of GPCRs structural determination, docking-based screening for novel potent and selective ligands is becoming an increa...

    journal_title:Journal of chemical information and modeling

    pub_type: 杂志文章

    doi:10.1021/ci400532b

    authors: Sabbadin D,Ciancetta A,Moro S

    更新日期:2014-01-27 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

  • What do we know about C28H14 and C30H14 benzenoid hydrocarbons and their evolution to related polymer strips?

    abstract::While critically reviewing the current status of what is known about C28H14 and C30H14 benzenoid isomers, which are ubiquitous pyrolytic constituents, some new insights will be presented. Representative isomers belonging to these benzenoid hydrocarbons are at the crossroads to homologous series that extend to infinite...

    journal_title:Journal of chemical information and modeling

    pub_type: 杂志文章

    doi:10.1021/ci050298i

    authors: Dias JR

    更新日期:2006-03-01 00:00:00

  • Loop Grafting between Similar Local Environments for Fc-Silent Antibodies.

    abstract::Reduction of the affinity of the fragment crystallizable (Fc) region with immune receptors by substitution of one or a few amino acids, known as Fc-silencing, is an established approach to reduce the immune effector functions of monoclonal antibody therapeutics. This approach to Fc-silencing, however, is problematic a...

    journal_title:Journal of chemical information and modeling

    pub_type: 杂志文章

    doi:10.1021/acs.jcim.9b01198

    authors: Lešnik S,Hodošček M,Podobnik B,Konc J

    更新日期:2020-11-23 00:00:00

  • AntiBac-Pred: A Web Application for Predicting Antibacterial Activity of Chemical Compounds.

    abstract::Discovery of new antibacterial agents is a never-ending task of medicinal chemistry. Every new drug brings significant improvement to patients with bacterial infections, but prolonged usage of antibacterials leads to the emergence of resistant strains. Therefore, novel active structures with new modes of action are re...

    journal_title:Journal of chemical information and modeling

    pub_type: 杂志文章

    doi:10.1021/acs.jcim.9b00436

    authors: Pogodin PV,Lagunin AA,Rudik AV,Druzhilovskiy DS,Filimonov DA,Poroikov VV

    更新日期:2019-11-25 00:00:00

  • Effect of structural stress on the flexibility and adaptability of HIV-1 protease.

    abstract::Resistance remains a major issue with regards to HIV-1 protease, despite the availability of numerous HIV-1 protease inhibitors and copious amounts of structural and binding data. In an effort to improve our understanding of how HIV-1 protease is able to "outsmart" new drugs, we have investigated the flexibility of HI...

    journal_title:Journal of chemical information and modeling

    pub_type: 杂志文章

    doi:10.1021/ci2000677

    authors: Oehme DP,Wilson DJ,Brownlee RT

    更新日期:2011-05-23 00:00:00

  • Structure-activity relationships in non-ligand binding pocket (non-LBP) diarylhydrazide antiandrogens.

    abstract::We report the synthesis and a study of the structure-activity relationships of a new series of diarylhydrazides as potential selective non-ligand binding pocket androgen receptor antagonists. Their biological activity as antiandrogens in the context of the development of treatments for castration resistant prostate ca...

    journal_title:Journal of chemical information and modeling

    pub_type: 杂志文章

    doi:10.1021/ci400189m

    authors: Caboni L,Egan B,Kelly B,Blanco F,Fayne D,Meegan MJ,Lloyd DG

    更新日期:2013-08-26 00:00:00

  • Accurate prediction of adsorption energies on graphene, using a dispersion-corrected semiempirical method including solvation.

    abstract::The accurate prediction of the adsorption energies of unsaturated molecules on graphene in the presence of water is essential for the design of molecules that can modify its properties and that can aid its processability. We here show that a semiempirical MO method corrected for dispersive interactions (PM6-DH2) can p...

    journal_title:Journal of chemical information and modeling

    pub_type: 杂志文章

    doi:10.1021/ci5003729

    authors: Vincent MA,Hillier IH

    更新日期:2014-08-25 00:00:00

  • Structural basis for the mutation-induced dysfunction of human CYP2J2: a computational study.

    abstract::Arachidonic acid is an essential fatty acid in cells, acting as a key inflammatory intermediate in inflammatory reactions. In cardiac tissues, CYP2J2 can adopt arachidonic acid as a major substrate to produce epoxyeicosatrienoic acids (EETs), which can protect endothelial cells from ischemic or hypoxic injuries and ha...

    journal_title:Journal of chemical information and modeling

    pub_type: 杂志文章

    doi:10.1021/ci400003p

    authors: Cong S,Ma XT,Li YX,Wang JF

    更新日期:2013-06-24 00:00:00

  • Molecular modeling of DNA cross-linking analogues based on the azinomycin scaffold.

    abstract::In this work, we present molecular modeling studies carried out using six DNA sequences and six azinomycin analogues, including the naturally occurring compound azinomycin B, selected on the basis of known cell cytotoxicity and structural analogies (epoxide and aziridine alkylating moieties). Among several computation...

    journal_title:Journal of chemical information and modeling

    pub_type: 杂志文章

    doi:10.1021/ci0496595

    authors: Alcaro S,Ortuso F,Coleman RS

    更新日期:2005-05-01 00:00:00

  • PyCGTOOL: Automated Generation of Coarse-Grained Molecular Dynamics Models from Atomistic Trajectories.

    abstract::Development of coarse-grained (CG) molecular dynamics models is often a laborious process which commonly relies upon approximations to similar models, rather than systematic parametrization. PyCGTOOL automates much of the construction of CG models via calculation of both equilibrium values and force constants of inter...

    journal_title:Journal of chemical information and modeling

    pub_type: 杂志文章

    doi:10.1021/acs.jcim.7b00096

    authors: Graham JA,Essex JW,Khalid S

    更新日期:2017-04-24 00:00:00

  • Three-dimensional quantitative structure-activity relationship of nucleosides acting at the A3 adenosine receptor: analysis of binding and relative efficacy.

    abstract::The binding affinity and relative maximal efficacy of human A3 adenosine receptor (AR) agonists were each subjected to ligand-based three-dimensional quantitative structure-activity relationship analysis. Comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) used a...

    journal_title:Journal of chemical information and modeling

    pub_type: 杂志文章

    doi:10.1021/ci600501z

    authors: Kimand SK,Jacobson KA

    更新日期:2007-05-01 00:00:00

  • Effect of input differences on the results of docking calculations.

    abstract::The sensitivity of docking calculations to the geometry of the input ligand was studied. It was found that even small changes in the ligand input conformation can lead to large differences in the geometries and scores of the resulting docked poses. The accuracy of docked poses produced from different ligand input stru...

    journal_title:Journal of chemical information and modeling

    pub_type: 杂志文章

    doi:10.1021/ci9000629

    authors: Feher M,Williams CI

    更新日期:2009-07-01 00:00:00

  • ColBioS-FlavRC: a collection of bioselective flavonoids and related compounds filtered from high-throughput screening outcomes.

    abstract::Flavonoids, the vastest class of natural polyphenols, are extensively investigated for their multiple benefits on human health. Due to their physicochemical or biological properties, many representatives are considered to exhibit low selectivity among various protein targets or to plague high-throughput screening (HTS...

    journal_title:Journal of chemical information and modeling

    pub_type: 杂志文章

    doi:10.1021/ci5002668

    authors: Avram SI,Pacureanu LM,Bora A,Crisan L,Avram S,Kurunczi L

    更新日期:2014-08-25 00:00:00

  • Allosteric Response of DNA Recognition Helices of Catabolite Activator Protein to cAMP and DNA Binding.

    abstract::The homodimeric catabolite activator protein (CAP) regulates the transcription of several bacterial genes based on the cellular concentration of cyclic adenosine monophosphate (cAMP). The binding of cAMP to CAP triggers allosteric communication between the cAMP binding domains (CBD) and DNA binding domains (DBD) of CA...

    journal_title:Journal of chemical information and modeling

    pub_type: 杂志文章

    doi:10.1021/acs.jcim.0c00617

    authors: Prabhakant A,Panigrahi A,Krishnan M

    更新日期:2020-12-28 00:00:00

  • Visualization of Solar Cell Library Space by Dimensionality Reduction Methods.

    abstract::Visualizing high-dimensional data by projecting them into a two- or three-dimensional space is a popular approach in many scientific fields, including computer-aided drug design and cheminformatics. In contrast, dimensionality reduction techniques have been far less explored for materials informatics. Nevertheless, si...

    journal_title:Journal of chemical information and modeling

    pub_type: 杂志文章

    doi:10.1021/acs.jcim.8b00552

    authors: Kaspi O,Yosipof A,Senderowitz H

    更新日期:2018-12-24 00:00:00

  • Assessment of the Cruzain Cysteine Protease Reversible and Irreversible Covalent Inhibition Mechanism.

    abstract::Reversible and irreversible covalent ligands are advanced cysteine protease inhibitors in the drug development pipeline. K777 is an irreversible inhibitor of cruzain, a necessary enzyme for the survival of the Trypanosoma cruzi (T. cruzi) parasite, the causative agent of Chagas disease. Despite their importance, irrev...

    journal_title:Journal of chemical information and modeling

    pub_type: 杂志文章

    doi:10.1021/acs.jcim.9b01138

    authors: Silva JRA,Cianni L,Araujo D,Batista PHJ,de Vita D,Rosini F,Leitão A,Lameira J,Montanari CA

    更新日期:2020-03-23 00:00:00

  • FOG: Fragment Optimized Growth algorithm for the de novo generation of molecules occupying druglike chemical space.

    abstract::An essential feature of all practical de novo molecule generating programs is the ability to focus the potential combinatorial explosion of grown molecules on a desired chemical space. It is a daunting task to balance the generation of new molecules with limitations on growth that produce desired features such as stab...

    journal_title:Journal of chemical information and modeling

    pub_type: 杂志文章

    doi:10.1021/ci9000458

    authors: Kutchukian PS,Lou D,Shakhnovich EI

    更新日期:2009-07-01 00:00:00

  • CHARMMing: a new, flexible web portal for CHARMM.

    abstract::A new web portal for the CHARMM macromolecular modeling package, CHARMMing (CHARMM interface and graphics, http://www.charmming.org), is presented. This tool provides a user-friendly interface for the preparation, submission, monitoring, and visualization of molecular simulations (i.e., energy minimization, solvation,...

    journal_title:Journal of chemical information and modeling

    pub_type: 杂志文章

    doi:10.1021/ci800133b

    authors: Miller BT,Singh RP,Klauda JB,Hodoscek M,Brooks BR,Woodcock HL 3rd

    更新日期:2008-09-01 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

  • Advantages of Relative versus Absolute Data for the Development of Quantitative Structure-Activity Relationship Classification Models.

    abstract::The appropriate selection of a chemical space represented by the data set, the selection of its chemical data representation, the development of a correct modeling process using a robust and reproducible algorithm, and the performance of an exhaustive training and external validation determine the usability and reprod...

    journal_title:Journal of chemical information and modeling

    pub_type: 杂志文章

    doi:10.1021/acs.jcim.7b00492

    authors: Ruiz IL,Gómez-Nieto MÁ

    更新日期:2017-11-27 00:00:00

  • Dynamics of noncovalent interactions in all-α and all-β class proteins: implications for the stability of amyloid aggregates.

    abstract::A fully folded functional protein is stabilized by several noncovalent interactions. When a protein undergoes conformational motions, the existing noncovalent interactions may be maintained. They may also break or new interactions may be formed. Knowledge of the dynamical nature of the different types of noncovalent i...

    journal_title:Journal of chemical information and modeling

    pub_type: 杂志文章

    doi:10.1021/ci200302q

    authors: Jain A,Sankararamakrishnan R

    更新日期:2011-12-27 00:00:00

  • 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 thi...

    journal_title:Journal of chemical information and modeling

    pub_type: 杂志文章

    doi:10.1021/acs.jcim.6b00763

    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

    更新日期:2017-06-26 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

  • Exploring inhibitor release pathways in histone deacetylases using random acceleration molecular dynamics simulations.

    abstract::Molecular channel exploration perseveres to be the prominent solution for eliciting structure and accessibility of active site and other internal spaces of macromolecules. The volume and silhouette characterization of these channels provides answers for the issues of substrate access and ligand swapping between the ob...

    journal_title:Journal of chemical information and modeling

    pub_type: 杂志文章

    doi:10.1021/ci200584f

    authors: Kalyaanamoorthy S,Chen YP

    更新日期:2012-02-27 00:00:00

  • Adaptive configuring of radial basis function network by hybrid particle swarm algorithm for QSAR studies of organic compounds.

    abstract::The configuring of a radial basis function network (RBFN) consists of selecting the network parameters (centers and widths in RBF units and weights between the hidden and output layers) and network architecture. The issues of suboptimum and overfitting, however, often occur in RBFN configuring. This paper presented a ...

    journal_title:Journal of chemical information and modeling

    pub_type: 杂志文章

    doi:10.1021/ci600218d

    authors: Zhou YP,Jiang JH,Lin WQ,Zou HY,Wu HL,Shen GL,Yu RQ

    更新日期:2006-11-01 00:00:00

  • BFMP: a method for discretizing and visualizing pyranose conformations.

    abstract::We report a new classification method for pyranose ring conformations called Best-fit, Four-Membered Plane (BFMP), which describes pyranose ring conformations based on reference planes defined by four atoms. The method is able to characterize all asymmetrical and symmetrical shapes of a pyran ring, is readily automate...

    journal_title:Journal of chemical information and modeling

    pub_type: 杂志文章

    doi:10.1021/ci500325b

    authors: Makeneni S,Foley BL,Woods RJ

    更新日期:2014-10-27 00:00:00