Synthesis, characterization and in-silico assessment of novel thiazolidinone derivatives for cyclin-dependent kinases-2 inhibitors

Abdullah, Jasim Ali; Aldahham, Bilal J M; Rabeea, Muwafaq Ayesh; Asmary, Fatmah Ali; Alhajri, Hassna Mohammed; Islam, Ataul

doi:10.1016/j.molstruc.2020.129311

Cited by 18 publications

(20 citation statements)

References 64 publications

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“…In the present study, the binding free energy was calculated using the molecular mechanics-generalized born surface area (MM-GBSA) method [ 55 ] using the last 10000 frames of each system. The same approach was used in our previous published work [ 56 ]. In particular, the following mathematical derivation was followed for MM-GBSA based binding free energy estimation for the protein-ligand complexes.…”

Section: Methodsmentioning

confidence: 99%

Identification of potent food constituents as SARS-CoV-2 papain-like protease modulators through advanced pharmacoinformatics approaches

Bhowmick

Saha

AlFaris

et al. 2022

Journal of Molecular Graphics and Modelling

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The current ongoing pandemic of COVID-19 urges immediate treatment measures for controlling the highly contagious SARS-CoV-2 infections. The papain-like protease (PLpro), which is released from nsp3, is presently being evaluated as a significant anti-viral drug target for COVID-19 therapy development. Particularly, PLpro is implicated in the cleavage of viral polyproteins and antagonizes the host innate immune response through its deubiquitinating and deISGylating actions, thus making it a high-profile antiviral therapeutic target. The present study reports a few specific food compounds that can bind tightly with the SARS-CoV-2 PLpro protein identified through extensive computational screening techniques. Precisely, extensive advanced computational approaches combining target-based virtual screening, particularly employing sub-structure based similarity search, molecular docking, molecular dynamics (MD) simulations, and MM-GBSA based binding free energy calculations have been employed for the identification of the most promising food compounds with substantial functional implications as SARS-CoV-2 PLpro protein inhibitors/modulators. Observations from the present research investigation also provide a deeper understanding of the binding modes of the proposed four food compounds with SARS-CoV-2 PLpro protein. In docking analyses, all compounds have established essential inter-molecular interaction profiles at the active site cavity of the SARS-CoV-2 PLpro protein. Similarly, the long-range 100 ns conventional MD simulation studies also provided an in-depth understanding of probable interactions and dynamic behaviour of the SARS-CoV-2 PLpro protein-food compound complexes. Binding free energies of all molecular systems revealed a strong interaction affinity of food compounds towards the SARS-CoV-2 PLpro protein. Moreover, clear-cut comparative analyses against the known standard inhibitor also suggest that proposed food compounds may act as potential active chemical entities for modulating the action of the SARS-CoV-2 PLpro protein.

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Section: Methodsmentioning

confidence: 99%

Identification of potent food constituents as SARS-CoV-2 papain-like protease modulators through advanced pharmacoinformatics approaches

Bhowmick

Saha

AlFaris

et al. 2022

Journal of Molecular Graphics and Modelling

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“…Both models calculate binding free energies by combining molecular mechanics calculations and continuum solvation models. Both approaches are used in a number of interesting studies [55][56][57][58] included by our research group [59][60][61]. Hou et al [62] considered both the approaches and calculated binding free energy of several ligands.…”

Section: Binding Free Energy Calculation Through Mm-gbsa Approachmentioning

confidence: 99%

Pharmacoinformatics-based identification of transmembrane protease serine-2 inhibitors from Morus Alba as SARS-CoV-2 cell entry inhibitors

et al. 2021

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Transmembrane protease serine-2 (TMPRSS2) is a cell-surface protein expressed by epithelial cells of specific tissues including those in the aerodigestive tract. It helps the entry of novel coronavirus (n-CoV) or Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in the host cell. Successful inhibition of the TMPRSS2 can be one of the crucial strategies to stop the SARS-CoV-2 infection. In the present study, a set of bioactive molecules from Morus alba Linn. were screened against the TMPRSS2 through two widely used molecular docking engines such as Autodock vina and Glide. Molecules having a higher binding affinity toward the TMPRSS2 compared to Camostat and Ambroxol were considered for in-silico pharmacokinetic analyses. Based on acceptable pharmacokinetic parameters and drug-likeness, finally, five molecules were found to be important for the TMPRSS2 inhibition. A number of bonding interactions in terms of hydrogen bond and hydrophobic interactions were observed between the proposed molecules and ligand-interacting amino acids of the TMPRSS2. The dynamic behavior and stability of best-docked complex between TRMPRSS2 and proposed molecules were assessed through molecular dynamics (MD) simulation. Several parameters from MD simulation have suggested the stability between the protein and ligands. Binding free energy of each molecule calculated through MM-GBSA approach from the MD simulation trajectory suggested strong affection toward the TMPRSS2. Hence, proposed molecules might be crucial chemical components for the TMPRSS2 inhibition. Graphic abstract

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“…The solid product filtered, dried and recrystallized from absolute ethanol. The chemical and spectral data of the compounds are given in table (1)(2)(3)(4)(5)(6)(7). To a mixture consist of (0.001 mole) glycine, (3-6 mL) of 30% sodium hydroxide solution, (15 mL) of benzene and (0.1 gm) benzyl tributyl ammonium chloride (BTBAC).…”

Section: General Procedures For Synthesis Of Schiff Bases(comp 1 and 2): 4-(3-hydroxybenzylideneamino)antipyrine (Comp 1) And 4-(4-nitrobmentioning

confidence: 99%

“…physical properties and other characteristics for the synthesis Schiff base derivatives(3,4) SYNTHESIS OF SOME IMIDAZOLIDINONE COMPOUNDS UNDER PHASE TRANSFER CONDITIONS.. ..…”

mentioning

confidence: 99%

Synthesis of some Imidazolidinone compounds under phase transfer conditions and photo cleavages studies of molecular for these compounds

Abdullah

Yhya²,

Toohi³

2021

Egypt. J. Chem.

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In this paper, two of the new antipyrine heterocyclic derivatives have been synthesized via the formation of Schiff bases. The Schiff bases compounds were generated from the reaction of 4-Ameno-antipyrine (4-AAP) with 3-hydroxybenzaldehyde and 4-nitrobenzaldehyde, which was converted to imidazolidinone compounds by reaction with glycine. The reactions were monitored by Thin Layer Chromatography (TLC). The structure of the prepared compounds was confirmed by physical and available spectroscopic data, i.e., FTIR, 1 HNMR, 13 C-NMR, GC-Mass and HRMs.

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Synthesis, characterization and in-silico assessment of novel thiazolidinone derivatives for cyclin-dependent kinases-2 inhibitors

Cited by 18 publications

References 64 publications

Identification of potent food constituents as SARS-CoV-2 papain-like protease modulators through advanced pharmacoinformatics approaches

Identification of potent food constituents as SARS-CoV-2 papain-like protease modulators through advanced pharmacoinformatics approaches

Pharmacoinformatics-based identification of transmembrane protease serine-2 inhibitors from Morus Alba as SARS-CoV-2 cell entry inhibitors

Synthesis of some Imidazolidinone compounds under phase transfer conditions and photo cleavages studies of molecular for these compounds

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