Synthesis, homology modeling, molecular docking, dynamics, and antifungal screening of new 4-hydroxycoumarin derivatives as potential chitinase inhibitors

Batran, Rasha Z.; Khedr, Mohammed A.; Latif, N.; Aty, Abeer A. Abd El; Shehata, Abeer N.

doi:10.1016/j.molstruc.2018.11.099

Cited by 22 publications

(18 citation statements)

References 44 publications

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“…To address the stability of docked ligand into the active site of target protein, next, we carried out the molecular dynamic (MD) simulations for 10 ns using GROMACS 2020.1 [ 40 , 41 ] for the selected hits from results obtained through docking followed by manual analysis. However, MD run of ≤ 10 ns has been regarded as the more suitable and satisfactory for preliminary in silico studies as evident in scientific literatures [42] , [43] , [44] , [45] , [46] , [47] . The time-dependent stability of the ligand in the active site was studied using statistical tools such as root mean square deviation (RMSD), root mean square fluctuation (RMSF), radius of gyration (RoG), solvent accessible surface area (SASA) and hydrogen bonds (HB).…”

Section: Resultsmentioning

confidence: 99%

In search of RdRp and Mpro inhibitors against SARS CoV-2: Molecular docking, molecular dynamic simulations and ADMET analysis

Gajjar

Dhameliya

Shah

2021

Journal of Molecular Structure

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Corona Virus Disease 2019 (COVID-19) caused by Severe Acute Respiratory Syndrome coronavirus (SARS CoV-2) has been declared a worldwide pandemic by WHO recently. The complete understanding of the complex genomic structure of SARS CoV-2 has enabled the use of computational tools in search of SARS CoV-2 inhibitors against the multiple proteins responsible for its entry and multiplication in human cells. With this endeavor, 177 natural, anti-viral chemical entities and their derivatives, selected through the critical analysis of the literatures, were studied using pharmacophore screening followed by molecular docking against RNA dependent RNA polymerase and main protease. The identified hits have been subjected to molecular dynamic simulations to study the stability of ligand-protein complexes followed by ADMET analysis and Lipinski filters to confirm their drug likeliness. It has led to an important start point in the drug discovery and development of therapeutic agents against SARS CoV-2.

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Section: Resultsmentioning

confidence: 99%

In search of RdRp and Mpro inhibitors against SARS CoV-2: Molecular docking, molecular dynamic simulations and ADMET analysis

Gajjar

Dhameliya

Shah

2021

Journal of Molecular Structure

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“…According to these findings, we suggested that the efficacy of grape marc in stimulating cell-cultured chitinolytic activity could be mainly ascribed to the most quantitatively represented classes of flavonoids (i.e., the monomer catechin, dimeric procyanidins B2 + B4, and the flavonols quercetin and syringetin-glucoside and galactoside). Recently, 4-hydroxycoumarin derivatives have been selected for their predicted highly binding affinity for fungal chitinase and considered as new potential antifungal inhibitors [25]. It is conceivable that some, if not all, of these phenolic molecules, could directly exert their stimulation on the chitinase activity measured in grapevine cells, depending on their concentration and affinity to the catalytic site.…”

Section: Discussionmentioning

confidence: 99%

Bioactive Polyphenols Modulate Enzymes Involved in Grapevine Pathogenesis and Chitinase Activity at Increasing Complexity Levels

Filippi

Petrussa

Boscutti

et al. 2019

IJMS

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The reduction of synthetic chemistry use in modern viticulture relies on either the biological control of microorganisms or the induction of pathogenesis-related proteins. In the present study, the effects of hydro-alcoholic plant extracts (PEs) (i.e., by-products of Vitis vinifera L., leaves of Olea europaea L. and Ailanthus altissima (Mill.) Swingle) were tested on purified enzymes activity involved in plant-pathogen interactions. The polyphenolic composition was assayed and analyzed to characterize the extract profiles. In addition, suspension cell cultures of grapevine were treated with PEs to study their modulation of chitinase activity. Application of grape marc’s PE enhanced chitinase activity at 4 g L−1. Additionally, foliar treatment of grape marc’s PE at two doses (4 g L−1 and 800 g L−1) on grapevine cuttings induced a concentration-dependent stimulation of chitinase activity. The obtained results showed that the application of bioactive compounds based on PEs, rich in phenolic compounds, was effective both at in vitro and ex/in vivo level. The overall effects of PEs on plant-pathogen interaction were further discussed by applying a multi-criteria decision analysis, showing that grape marc was the most effective extract.

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“…To study the stability of ligand into the binding site of protein, molecular dynamics (MD) simulations provide the better understanding of ligand through several statistical parameters [ 48 , 49 ]. Several scientific literatures support the reliability and satisfactory stability for the MD run (≤ 10 ns) through in silico endeavor [50] , [51] , [52] , [53] , [54] , [55] . In a similar line of approach, the hit complexes obtained from the evaluation of ADMET and drug-likeliness properties, were subjected for MD simulations using GROMACS 2020.1 to assess the stability of the stability of the ligands ( 2 - 3 ) in the active site of docked complex at various time points up to 10 ns [ 56 , 57 ].…”

Section: Resultsmentioning

confidence: 87%

In search of SARS CoV-2 replication inhibitors: Virtual screening, molecular dynamics simulations and ADMET analysis

Nagar

Gajjar

Dhameliya

2021

Journal of Molecular Structure

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Severe acute respiratory syndrome has relapsed recently as novel coronavirus causing a life threat to the entire world in the absence of an effective therapy. To hamper the replication of the deadly SARS CoV-2 inside the host cells, systematic in silico virtual screening of total 267,324 ligands from Asinex EliteSynergy and BioDesign libraries has been performed using AutoDock Vina against RdRp. The molecular modeling studies revealed the identification of twenty-one macrocyclic hits ( 2 - 22 ) with better binding energy than remdesivir ( 1 ), marketed SARS CoV-2 inhibitor. Further, the analysis using rules for drug-likeness and their ADMET profile revealed the candidature of these hits due to superior oral bioavailability and druggability. Further, the MD simulation studies of top two hits ( 2 and 3 ) performed using GROMACS 2020.1 for 10 ns revealed their stability into the docked complexes. These results provide an important breakthrough in the design of macrocyclic hits as SARS CoV-2 RNA replicase inhibitor.

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Synthesis, homology modeling, molecular docking, dynamics, and antifungal screening of new 4-hydroxycoumarin derivatives as potential chitinase inhibitors

Cited by 22 publications

References 44 publications

In search of RdRp and Mpro inhibitors against SARS CoV-2: Molecular docking, molecular dynamic simulations and ADMET analysis

In search of RdRp and Mpro inhibitors against SARS CoV-2: Molecular docking, molecular dynamic simulations and ADMET analysis

Bioactive Polyphenols Modulate Enzymes Involved in Grapevine Pathogenesis and Chitinase Activity at Increasing Complexity Levels

In search of SARS CoV-2 replication inhibitors: Virtual screening, molecular dynamics simulations and ADMET analysis

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