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


: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.


J Chem Inf Model


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




Has Abstract


2017-06-26 00:00:00












  • Isomerization and Decomposition of 2-Methylfuran with External Forces.

    abstract::The primary goal of this project was to evaluate the performance of the Standard and Enforced Geometry Optimization (SEGO) method which we have recently developed. The SEGO method has been designed for an automatic location of multiple minima on the molecular Potential Energy Surface (PES), and its usefulness has been...

    journal_title:Journal of chemical information and modeling

    pub_type: 杂志文章


    authors: Brzyska A,Woliński K

    更新日期:2019-08-26 00:00:00

  • Identification of ligand templates using local structure alignment for structure-based drug design.

    abstract::With a rapid increase in the number of high-resolution protein-ligand structures, the known protein-ligand structures can be used to gain insight into ligand-binding modes in a target protein. On the basis of the fact that the structurally similar binding sites share information about their ligands, we have developed ...

    journal_title:Journal of chemical information and modeling

    pub_type: 杂志文章


    authors: Lee HS,Im W

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  • Efficiency of Stratification for Ensemble Docking Using Reduced Ensembles.

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    journal_title:Journal of chemical information and modeling

    pub_type: 杂志文章


    authors: Xie B,Clark JD,Minh DDL

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  • Critical Assessment of the Hildebrand and Hansen Solubility Parameters for Polymers.

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    pub_type: 杂志文章


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  • Interpretation of Quantitative Structure-Activity Relationship Models: Past, Present, and Future.

    abstract::This paper is an overview of the most significant and impactful interpretation approaches of quantitative structure-activity relationship (QSAR) models, their development, and application. The evolution of the interpretation paradigm from "model → descriptors → (structure)" to "model → structure" is indicated. The lat...

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    pub_type: 杂志文章,评审


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    journal_title:Journal of chemical information and modeling

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    journal_title:Journal of chemical information and modeling

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    pub_type: 杂志文章


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    journal_title:Journal of chemical information and modeling

    pub_type: 杂志文章


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  • Coarse-Grained Prediction of Peptide Binding to G-Protein Coupled Receptors.

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    journal_title:Journal of chemical information and modeling

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    authors: Sun Y,Huang J,Duan X,Ding F

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    abstract::Protein farnesyltransferase (FTase) is an important anticancer drug target. In an effort to develop isoprenoid diphosphate-based FTase inhibitors, striking variations have been observed in the ability of conservatively modified analogues to bind to the enzyme. For example, 2Z-GGPP is an alternative substrate with high...

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    journal_title:Journal of chemical information and modeling

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    journal_title:Journal of chemical information and modeling

    pub_type: 信件


    authors: Kang M,Chakraborty K,Loverde SM

    更新日期:2018-06-25 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


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    更新日期:2019-02-25 00:00:00

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    abstract::Grass weed populations resistant to acetyl-CoA carboxylase-inhibiting (ACCase; EC herbicides represent a major problem for the sustainable development of modern agriculture. In the present study, extensive computational simulations, including homology modeling, molecular dynamics (MD) simulations, and molecul...

    journal_title:Journal of chemical information and modeling

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  • Exploration of the accessible chemical space of acyclic alkanes.

    abstract::Saturated acyclic alkanes show steric strain if they are highly branched and, in extreme cases, fall apart rapidly at room temperature. Consequently, attempts to count the number of isomeric forms for a given molecular formula that neglect this physical consideration will inevitably overestimate the size of the availa...

    journal_title:Journal of chemical information and modeling

    pub_type: 杂志文章


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  • Accurate Estimation of pKb Values for Amino Groups from Surface Electrostatic Potential (VS,min) Calculations: The Isoelectric Points of Amino Acids as a Case Study.

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    journal_title:Journal of chemical information and modeling

    pub_type: 杂志文章


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    journal_title:Journal of chemical information and modeling

    pub_type: 杂志文章


    authors: Izairi R,Kamberaj H

    更新日期:2017-10-23 00:00:00

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    journal_title:Journal of chemical information and modeling

    pub_type: 杂志文章


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