Molecular Dynamic Simulation Analysis on the Inclusion Complexation of Plumbagin with β-Cyclodextrin Derivatives in Aqueous Solution

Jitapunkul, Kulpavee; Toochinda, Pisanu; Lawtrakul, Luckhana

doi:10.3390/molecules26226784

Cited by 6 publications

(6 citation statements)

References 28 publications

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“…From the molecular-dynamics simulations, the root-mean-square deviation (RMSD), root-mean-square fluctuation (RMSF), radius of gyration (Rg), and the solvent-accessible surface area (SASA) of the BI-2852 and lead flavonoids docked with the KRAS G12D mutant were predicted. The RMSD trajectory provides information about the protein stability upon ligand binding, RMSF provides information about the average mobility of the c-α atoms of amino-acid residues, Rg provides information about the folding and rigidity properties of the protein, while SASA provides information about the protein’s surface area available for water molecules [ 38 , 53 ]. In general, if the RMSD is lower, then the stability will be higher.…”

Section: Discussionmentioning

confidence: 99%

Identification of Dietary Bioflavonoids as Potential Inhibitors against KRAS G12D Mutant—Novel Insights from Computer-Aided Drug Discovery

Ramalingam

Balakrishnan²,

Senthilnathan

et al. 2023

CIMB

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The KRAS G12D mutation is very frequent in many cancers, such as pancreatic, colon and lung, and has remained undruggable for the past three decades, due to its smooth surface and lack of suitable pockets. Recent small pieces of evidence suggest that targeting the switch I/II of KRAS G12D mutant could be an efficient strategy. Therefore, in the present study, we targeted the switch I (residues 25–40) and switch II (residues 57–76) regions of KRAS G12D with dietary bioflavonoids in comparison with the reference KRAS SI/II inhibitor BI-2852. Initially, we screened 925 bioflavonoids based on drug-likeness properties, and ADME properties and selected 514 bioflavonoids for further studies. Molecular docking resulted in four lead bioflavonoids, namely 5-Dehydroxyparatocarpin K (L1), Carpachromene (L2), Sanggenone H (L3), and Kuwanol C (L4) with binding affinities of 8.8 Kcal/mol, 8.64 Kcal/mol, 8.62 Kcal/mol, and 8.58 Kcal/mol, respectively, in comparison with BI-2852 (−8.59 Kcal/mol). Further steered-molecular dynamics, molecular-dynamics simulation, toxicity, and in silico cancer-cell-line cytotoxicity predictions significantly support these four lead bioflavonoids as potential inhibitors of KRAS G12D SI/SII inhibitors. We finally conclude that these four bioflavonoids have potential inhibitory activity against the KRAS G12D mutant, and are further to be studied in vitro and in vivo, to evaluate their therapeutic potential and the utility of these compounds against KRAS G12D mutated cancers.

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Section: Discussionmentioning

confidence: 99%

Identification of Dietary Bioflavonoids as Potential Inhibitors against KRAS G12D Mutant—Novel Insights from Computer-Aided Drug Discovery

Ramalingam

Balakrishnan²,

Senthilnathan

et al. 2023

CIMB

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“…The binding energy (ΔG) and clustering information along with the coordinates for each docked conformation were recorded into the result files. The docked conformations with the lowest energy were selected for full geometry optimization, according to the previous studies [ 37 , 38 , 39 , 40 ].…”

Section: Methodsmentioning

confidence: 99%

Structural Investigation of Beta-Cyclodextrin Complexes with Cannabidiol and Delta-9-Tetrahydrocannabinol in 1:1 and 2:1 Host-Guest Stoichiometry: Molecular Docking and Density Functional Calculations

Triamchaisri

Toochinda

Lawtrakul

2023

IJMS

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The complexation of β-cyclodextrin (β-CD) with cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC) was investigated using molecular docking and M062X/6-31G(d,p) calculations. The calculations suggested two possible complex formations of 1:1 and 2:1 host-guest molecular ratio of β-CD with CBD and THC. The preferred orientation of all complexes in this study exhibited the hydrogen bonding between hydroxy-substituted benzene ring of CBD and THC with the β-CD’s secondary hydroxy groups at the wide rim. The calculated complexation energies indicate that formation of the 2:1 complexes (−83.53 to −135.36 kcal/mol) was more energetically favorable and chemically stable than the 1:1 complexes (−30.00 to −34.92 kcal/mol). However, the deformation energies of the host and the guest components in the 2:1 complexes (37.47–96.91 kcal/mol) are much higher than those in the 1:1 complexes (3.49–8.69 kcal/mol), which means the formation processes of the 2:1 complexes are more difficult due to the rigidity of the dimeric β-CDs. Therefore, the inclusion complexes of β-CD with CBD and THC are more likely to be in 1:1 host-guest ratio than in 2:1 molecular ratio. The results of this study supported the experimental results that the complexation constant of 1:1 β-CD/CBD (Ks = 300 M−1) is greater than that of 2:1 β-CDs/CBD (Kss = 0.833 M−1). Altogether, this study introduced the fitting parameters that could indicate the stability of the molecular fits in complex formation of each stoichiometry host-guest ratio, which are important for the assessment of the inclusion mechanisms as well as the relationships of reactants and products in chemical reactions.

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“…This is justified by its chemical structure, where the oxygens play an important role in stabilizing the positive charges in the PEDOT chains, thereby offering great opportunities for improving the interactions with biological entities [1][2][3][4][5][6]. Molecular encapsulation with the formation of inclusion complexes (ICs), which involves the presence of macrocyclic molecules (hosts) threaded over different monomers/polymers cores (guests) without any covalent bonds between them, has been extensively studied as a significant topic in both chemistry and biology [6][7][8][9][10]. A wide variety of host molecules have the ability to bind various guests into their interior cavity [6][7][8][9][10][11][12][13][14][15][16].…”

Section: Introductionmentioning

confidence: 99%

Inclusion Complexes of 3,4-Ethylenedioxythiophene with Per-Modified β- and γ-Cyclodextrins

Farcas¹,

Resmeriță²,

Balan-Porcăraşu³

et al. 2023

Molecules

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Herein, we report the synthesis of inclusion complexes (ICs) based on 3,4-ethylenedioxythiophene (EDOT) with permethylated β-cyclodextrins (TMe-βCD) and permethylated γ-cyclodextrins (TMe-γCD) host molecules. To prove the synthesis of such ICs, molecular docking simulation, UV-vis titrations in water, 1H-NMR, and H-H ROESY, as well as matrix-assisted laser desorption ionization mass spectroscopy (MALDI TOF MS) and thermogravimetric analysis (TGA) were carried out on each of the EDOT∙TMe-βCD and EDOT∙TMe-γCD samples. The results of computational investigations reveal the occurrence of hydrophobic interactions, which contribute to the insertion of the EDOT guest inside the macrocyclic cavities and a better binding of the neutral EDOT to TMe-βCD. The H-H ROESY spectra show correlation peaks between H-3 and H-5 of hosts and the protons of the guest EDOT, suggesting that the EDOT molecule is included inside the cavities. The MALDI TOF MS analysis of the EDOT∙TMe-βCD solutions clearly reveals the presence of MS peaks corresponding to sodium adducts of the species associated with the complex formation. The IC preparation shows remarkable improvements in the physical properties of EDOT, rendering it a plausible alternative to increasing its aqueous solubility and thermal stability.

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Molecular Dynamic Simulation Analysis on the Inclusion Complexation of Plumbagin with β-Cyclodextrin Derivatives in Aqueous Solution

Cited by 6 publications

References 28 publications

Identification of Dietary Bioflavonoids as Potential Inhibitors against KRAS G12D Mutant—Novel Insights from Computer-Aided Drug Discovery

Identification of Dietary Bioflavonoids as Potential Inhibitors against KRAS G12D Mutant—Novel Insights from Computer-Aided Drug Discovery

Structural Investigation of Beta-Cyclodextrin Complexes with Cannabidiol and Delta-9-Tetrahydrocannabinol in 1:1 and 2:1 Host-Guest Stoichiometry: Molecular Docking and Density Functional Calculations

Inclusion Complexes of 3,4-Ethylenedioxythiophene with Per-Modified β- and γ-Cyclodextrins

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