Structure–activity relationship and binding mode studies for a series of diketo-acids as HIV integrase inhibitors by 3D-QSAR, molecular docking and molecular dynamics simulations

Han, Dan; Su, Min; Tan, Jianjun; Li, Chun Hua; Zhang, Xiao Yi; Wang, Cun Xin

doi:10.1039/c6ra00713a

Cited by 10 publications

(8 citation statements)

References 51 publications

(60 reference statements)

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“…The binding free energy was decomposed into molecular mechanics terms and solvation energies, respectively. The van der Waals forces, electrostatic interactions, polar solvation energies and apolar solvation energies were computed [ 36 , 37 ].…”

Section: Methodsmentioning

confidence: 99%

Anti-HIV Potential of Beesioside I Derivatives as Maturation Inhibitors: Synthesis, 3D-QSAR, Molecular Docking and Molecular Dynamics Simulations

Zhao

et al. 2023

IJMS

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HIV-1 maturation is the final step in the retroviral lifecycle that is regulated by the proteolytic cleavage of the Gag precursor protein. As a first-in-class HIV-1 maturation inhibitor (MI), bevirimat blocks virion maturation by disrupting capsid-spacer peptide 1 (CA-SP1) cleavage, which acts as the target of MIs. Previous alterations of beesioside I (1) produced (20S,24S)-15ꞵ,16ꞵ-diacetoxy-18,24; 20,24-diepoxy-9,19-cyclolanostane-3ꞵ,25-diol 3-O-3′,3′-dimethylsuccinate (3, DSC), showing similar anti-HIV potency compared to bevirimat. To ascertain the binding modes of this derivative, further modification of compound 1 was conducted. Three-dimensional quantitative structure–activity relationship (3D-QSAR) analysis combined with docking simulations and molecular dynamics (MD) were conducted. Five new derivatives were synthesized, among which compound 3b showed significant activity against HIV-1NL4-3 with an EC50 value of 0.28 µM. The developed 3D-QSAR model resulted in great predictive ability with training set (r2 = 0.99, q2 = 0.55). Molecular docking studies were complementary to the 3D-QSAR analysis, showing that DSC was differently bound to CA-SP1 with higher affinity than that of bevirimat. MD studies revealed that the complex of the ligand and the protein was stable, with root mean square deviation (RMSD) values <2.5 Å. The above results provided valuable insights into the potential of DSC as a prototype to develop new antiviral agents.

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Section: Methodsmentioning

confidence: 99%

Anti-HIV Potential of Beesioside I Derivatives as Maturation Inhibitors: Synthesis, 3D-QSAR, Molecular Docking and Molecular Dynamics Simulations

Zhao

et al. 2023

IJMS

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“…Other efforts focused on HIV viruses, including HIV-1 protease (Li D. et al, 2014 ; Tzoupis et al, 2014 ; Chen J. Z. et al, 2015 ; Meher and Wang, 2015 ; Chen, 2016 ; Hu et al, 2016 ; Sroczynski et al, 2016 ; Xanthopoulos et al, 2016 ), gp120 (Wang J. H. et al, 2015 ), gp41 (Song et al, 2014 ), reverse transcriptase (Bernardo and Silva, 2014 ), HIV integrase (Quevedo et al, 2014 ; Han et al, 2016 ), and a comparative analysis of inhibitors for HIV-1 and HIV-2 proteases (Chen et al, 2014a ). Wright et al studied 9 inhibitor-bound HIV-1 proteases and compared the absolute binding free energies computed via MMPBSA and MMGBSA with and without normal mode-derived configurational entropy.…”

Section: Applications Of Mmpbsamentioning

confidence: 99%

Recent Developments and Applications of the MMPBSA Method

Wang

Greene

Xiao

et al. 2018

Front. Mol. Biosci.

443

327

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The Molecular Mechanics Poisson-Boltzmann Surface Area (MMPBSA) approach has been widely applied as an efficient and reliable free energy simulation method to model molecular recognition, such as for protein-ligand binding interactions. In this review, we focus on recent developments and applications of the MMPBSA method. The methodology review covers solvation terms, the entropy term, extensions to membrane proteins and high-speed screening, and new automation toolkits. Recent applications in various important biomedical and chemical fields are also reviewed. We conclude with a few future directions aimed at making MMPBSA a more robust and efficient method.

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“…The structure elucidation of curcumin analogous was performed using thin layer chromatography scanner (CAMAG TLC Scanner), Fourier transform infra-red spectrophotometer (FTIR, Shimadzu Prestige-21), highresolution mass spectrometer (HRMS/MS, Waters Xevo QtoF MS), and nuclear magnetic resonance spectrometer ( 1 H-NMR 500 MHz and 13 C-NMR 125 MHz, JEOL JNMECA, with an internal standard of TMS). Moreover, the melting point was determined using the electrothermal 9100 melting-point apparatus.…”

Section: Instrumentationmentioning

confidence: 99%

Molecular Docking, Synthesis and <i>In Vitro</i> Antiplasmodium Assay of Monoketone Curcumin Analogous from 2-Chlorobenzaldehyde

Mustika,

Astuti,

Marjan

2024

Indones. J. Chem.

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This research aimed to develop new curcumin analogous as antiplasmodium candidates. Six curcumin analogous (1-6) were proposed and docked against three Plasmodium falciparum receptors, namely PfENR, PfLDH, and PfATP6. The docking studies were carried out to predict the interaction among the compounds and receptors as well as their binding affinity. Three curcumin analogous (3, 4, and 6), which displayed specific interactions with the target receptors and possessed the lowest binding affinity were further proceeded to synthesis and in vitro antiplasmodium assay. Synthesis of the analogous 3, 4, and 6 was carried out from 2-chlorobenzadehyde via aldol condensation reaction and the products were obtained in good yields. Their in vitro antiplasmodium activities were then evaluated against P. falciparum FCR3 and 3D7 strains. The results showed that analogous 3, 4, and 6 were active against both strains with low levels of resistance. The in silico evaluation of the physicochemical and pharmacokinetic parameters showed that curcumin analogous displayed a better ADMET profile than curcumin, demonstrating the great potential of the developed curcumin analogous as antiplasmodium candidates.

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Structure–activity relationship and binding mode studies for a series of diketo-acids as HIV integrase inhibitors by 3D-QSAR, molecular docking and molecular dynamics simulations

Abstract: We explored the main factors affecting the activity of compounds by different statistical and computational methods.

Cited by 10 publications

References 51 publications

Anti-HIV Potential of Beesioside I Derivatives as Maturation Inhibitors: Synthesis, 3D-QSAR, Molecular Docking and Molecular Dynamics Simulations

Anti-HIV Potential of Beesioside I Derivatives as Maturation Inhibitors: Synthesis, 3D-QSAR, Molecular Docking and Molecular Dynamics Simulations

Recent Developments and Applications of the MMPBSA Method

Molecular Docking, Synthesis and <i>In Vitro</i> Antiplasmodium Assay of Monoketone Curcumin Analogous from 2-Chlorobenzaldehyde

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