Encapsulation mechanism of α-mangostin by β-cyclodextrin: Methods of molecular docking and molecular dynamics.
Ontology highlight
ABSTRACT:
SUBMITTER: Triwahyuningtyas D
PROVIDER: S-EPMC8300334 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Eugenol is a natural compound with well-known repellent activity. However, its pharmaceutical and cosmetic applications are limited, since this compound is highly volatile and thermolabile. Nanoencapsulation provides protection, stability, conservation, and controlled release for several compounds. Here, eugenol was included in β-cyclodextrin, and the complex was characterized through X-ray diffraction analysis (XRD) and Fourier-transform infrared spectroscopy (FTIR). Additionally, we used molecular dynamics simulations to explore the eugenol-β-cyclodextrin complex stability with temperature increases. Our computational result demonstrates details of the molecular interactions and conformational changes of the eugenol-β-cyclodextrin complex and explains its stability between temperatures 27°C and 48°C, allowing its use in formulations that are subjected to varied temperatures.
| S-EPMC9868465 | biostudies-literature
Project description:α-Mangostin (α-M), one of the active compounds in Garcinia mangostana peel, has been effectively used in wound healing. However, its poor solubility in aqueous solution causes low bioavailability for skin ulcers, hindering its application in wound healing. The aim of this study was to improve the solubility of α-M through complex formation with 2-hydroxypropyl-β-cyclodextrin (α-M/HP-β-CD CX) and to evaluate the healing activity of the complex. The α-M/HP-β-CD CX was incorporated in a sodium carboxymethylcellulose hydrogel (α-M/HP-β-CD CX HG), and the in vivo healing activity was examined in mice. Evaluation of α-M/HP-β-CD CX HG, including organoleptic evaluation, homogeneity, pH, spreadability, swelling ratio, consistency, scanning electron microscopy (SEM), and in vitro drug release, was carried out. The complex formation of α-M/HP-β-CD CX was confirmed by FTIR and PXRD analysis. The solubility of the α-M/HP-β-CD CX in water linearly increased about 11.7-fold compared to α-M alone, and by 3.5-fold compared to the α-M/HP-β-CD physical mixture (α-M/HP-β-CD CX PM). The α-M/HP-β-CD CX HG was homogenous, the pH was found to be in the neutral range, the spread area was 5 cm, and the consistency was stable until 14 days. SEM analysis showed that α-M/HP-β-CD CX HG surged due to the porous structure of the HG. In addition, in vitro release of α-M from α-M/HP-β-CD CX HG was considerably increased compared to α-M/HP-β-CD PM HG and α-M HG. Notably, in vivo evaluation in mice showed that α-M/HP-β-CD CX HG significantly accelerated the wound healing ability compared to other HGs. Thus, α-M/HP-β-CD CX HG has potential as a new formulation of α-M for wound healing therapy.
| S-EPMC7600479 | biostudies-literature
Project description:In this study, the encapsulation mechanism of oxyresveratrol and ?-cyclodextrin (?-CD) and hydroxypropyl-?-cyclodextrin (HP-?-CD) was studied. As this research shows, oxyresveratrol and two cyclodextrins (CDs) were able to form inclusion complexes in a 1:1 stoichiometry. However, the interaction with HP-?-CD was more efficient, showing up as higher encapsulation constant (KF) (35,864.72 ± 3415.89 M-1). The KF values exhibited a strong dependence on temperature and pH, which decreased as they increased. From the thermodynamic parameters (?H?, ?S?, and ?G?) of the oxyresveratrol loaded ?-CD (oxyresveratrol-?-CD) and HP-?-CD (oxyresveratrol-HP-?-CD), it could be seen that the complexation process was spontaneous and exothermic, and the main driving forces between oxyrsveratrol and CDs were hydrogen bonding and van der waals force. Besides, molecular docking combined with ¹H-NMR were used to explain the most possible mode of interactions between oxyresveratrol and CDs.
| S-EPMC6150350 | biostudies-literature
Project description:?-Mangostin (MGS) exhibits various pharmacological activities, including antioxidant, anticancer, antibacterial, and anti-inflammatory properties. However, its low water solubility is the major obstacle for its use in pharmaceutical applications. To increase the water solubility of MGS, complex formation with beta-cyclodextrins (?CDs), particularly with the native ?CD and/or its derivative 2,6-dimethyl-?-CD (DM?CD) is a promising technique. Although there have been several reports on the adsorption of ?CDs on the lipid bilayer, the release of the MGS/?CDs inclusion complex through the biological membrane remains unclear. In this present study, the release the MGS from the two different ?CDs (?CD and DM?CD) across the lipid bilayer was investigated. Firstly, the adsorption of the free MGS, free ?CDs, and inclusion complex formation was studied by conventional molecular dynamics simulation. The MGS in complex with those two ?CDs was able to spontaneously release free MGS into the inner membrane. However, both MGS and DM?CD molecules potentially permeated into the deeper region of the interior membrane, whereas ?CD only adsorbed at the outer membrane surface. The interaction between secondary rim of ?CD and the 1-palmitoeyl-2-oleoyl-glycero-3-phosphocholine (POPC) phosphate groups showed the highest number of hydrogen bonds (up to 14) corresponding to the favorable location of ?CD on the POPC membrane. Additionally, the findings suggested that electrostatic energy was the main driving force for ?CD adsorption on the POPC membrane, while van der Waals interactions played a predominant role in DM?CD adsorption. The release profile of MGS from the ?CDs pocket across the lipid bilayer exhibited two energy minima along the reaction coordinate associated with the permeation of the MGS molecule into the deeper region of the POPC membrane.
| S-EPMC7321106 | biostudies-literature
Project description:Acanthamoeba species are capable of causing amoebic keratitis (AK). As a monotherapy, alpha-mangostin is effective for the treatment of AK; however, its bioavailability is quite poor. Moreover, the efficacy of therapy is contingent on the parasite and virulent strains. To improve readiness against AK, it is necessary to find other derivatives with accurate target identification. Beta-tubulin (BT) has been used as a target for anti-Acanthamoeba (A. keratitis). In this work, therefore, a model of the BT protein of A. keratitis was constructed by homology modeling utilizing the amino acid sequence from NCBI (GenBank: JQ417907.1). Ramachandran Plot was responsible for validating the protein PDB. The verified BT PDB was used for docking with the specified ligand. Based on an improved docking score compared to alpha-mangostin (AM), two modified compounds were identified: 1,6-dihydroxy-7-methoxy-2,8-bis(3-methylbut-2-en-1-yl)-9H-xanthen-9-one (C1) and 1,6-dihydroxy-2,8-bis(3-methylbut-2-en-1-yl)-9H-xanthen-9-one (C2). In addition, molecular dynamics simulations were conducted to analyze the interaction characteristics of the two bound BT-new compound complexes. During simulations, the TRP9, ARG50, VAL52, and GLN122 residues of BT-C1 that align to the identical residues in BT-AM generate consistent hydrogen bond interactions with 0-3 and 0-2. However, the BT-C2 complex has a different binding site, TYR 258, ILE 281, and SER 302, and can form more hydrogen bonds in the range 0-4. Therefore, this study reveals that C1 and C2 inhibit BT as an additive or synergistic effect; however, further in vitro and in vivo studies are needed.
| S-EPMC9572066 | biostudies-literature
Project description:The safe and effective delivery of therapeutic genes into target cell interiors is of great importance in gene therapy. Chitosan has been extensively studied as a gene delivery carrier due to its good biocompatibility and biodegradability. Understanding the atomic interaction mechanism between chitosan and DNA is important in the design and application of chitosan-based drug and gene delivery systems. In this work, the interactions between single-stranded polynucleotides and different types of chitosan were systematically investigated by using molecular dynamics (MD) simulation. Our results demonstrate that the functional groups of chitosan, the types of base and length of polynucleotides regulate the interaction behavior between chitosan and polynucleotides. The encapsulation capacity of polynucleotide by chitosan is mainly balanced by two factors: the strength of polynucleotide binding to chitosan and the tendency of self-aggregation of polynucleotide in the solution. For -NH3+ chitosan, due to the strong electrostatic interaction, especially the H-bond between -NH3+ groups in chitosan and phosphate groups in polynucleotide, the aggregation effect could be partially eliminated. The good dispersal capacity of polynucleotides may improve the encapsulation of polynucleotides by chitosan, and hence increase the delivery and transfection efficiency of chitosan-based gene carrier.
| S-EPMC5506017 | biostudies-literature
Project description:The interaction between myofibrillar proteins (MPs) and capsaicin (CAP) was investigated using multispectral, molecular docking, and molecular dynamics simulation methods. The resulting complex increased the hydrophobicity of the tryptophan and tyrosine microenvironment as revealed by fluorescence spectral analysis. The fluorescence burst mechanism study indicated that the fluorescence burst of CAP on the MPs was a static one (Kq = 1.386 × 1012 m-1s-1) and that CAP could bind with MPs well (Ka = 3.31 × 104 L/mol, n = 1.09). The analysis of circular dichroism demonstrated that the interaction between CAP and MPs caused a decrease in the α-helical structure of MPs. The complexes formed exhibited lower particle size and higher absolute ζ potential. Furthermore, hydrogen bonding, van der Waals forces, and hydrophobic interactions were found to be the primary factors facilitating the interaction between CAP and MPs, as suggested by molecular docking models and molecular dynamics simulations.
| S-EPMC10314199 | biostudies-literature
Project description:Cyclodextrins (CDs) are widely used in drug delivery, catalysis, food and separation processes. In this work, a comprehensive simulation study on the diffusion of the native α-, β- and γ-CDs in aqueous solutions is carried out using Molecular Dynamics simulations. The effect of the system size on the computed self-diffusivity is investigated and it is found that the required correction can be as much as 75% of the final value. The effect of the water force field is examined and it is shown that the q4md-CD/TIP4P/2005 force field combination predicts the experimentally measured self-diffusion coefficients of CDs very accurately. The self-diffusion coefficients of the three native CDs were also computed in aqueous-NaCl solutions using the Joung and Cheatham (JC) and the Madrid-2019 force fields. It is found that Na + ions have higher affinity towards the CDs when the JC force field is used and for this reason the predicted diffusivity of CDs is lower compared to simulations using the Madrid-2019 force field. As a model system for drug delivery and waste-water treatment applications, the diffusion of the β-CD:Ibuprofen inclusion complex in water is studied. In agreement with experiments for similar components, it is shown that the inclusion complex and the free β-CD have almost equal self-diffusion coefficients. Our analysis revealed that this is most likely caused by the almost full inclusion of the ibuprofen in the cavity of the β-CD. Our findings show that Molecular Dynamics simulation can be used to provide reasonable diffusivity predictions, and to obtain molecular-level understanding useful for industrial applications of CDs.
| S-EPMC7529625 | biostudies-literature
Project description:2-Hydroxypropyl-β-cyclodextrin (HPβCD) has unique properties to enhance the stability and the solubility of low water-soluble compounds by inclusion complexation. An understanding of the structural properties of HPβCD and its derivatives, based on the number of 2-hydroxypropyl (HP) substituents at the α-d-glucopyranose subunits is rather important. In this work, replica exchange molecular dynamics simulations were performed to investigate the conformational changes of single- and double-sided HP-substitution, called 6-HPβCDs and 2,6-HPβCDs, respectively. The results show that the glucose subunits in both 6-HPβCDs and 2,6-HPβCDs have a lower chance of flipping than in βCD. Also, HP groups occasionally block the hydrophobic cavity of HPβCDs, thus hindering drug inclusion. We found that HPβCDs with a high number of HP-substitutions are more likely to be blocked, while HPβCDs with double-sided HP-substitutions have an even higher probability of being blocked. Overall, 6-HPβCDs with three and four HP-substitutions are highlighted as the most suitable structures for guest encapsulation, based on our conformational analyses, such as structural distortion, the radius of gyration, circularity, and cavity self-closure of the HPβCDs.
| S-EPMC6401915 | biostudies-literature
Project description:In the presented work, the stability of the formation of inclusion complexes of dodecanoic acid (lauric acid) with three cyclodextrins, α-cyclodextrin, β-cyclodextrin and 2-HP-β-cyclodextrin, was analyzed from the point of view of the size of the cavity in cyclodextrins, their molar mass and the structure of the studied fatty acid. The measurements were made in a wide temperature range of 283.15-318.15K. The conductometric method was used for these studies. The results obtained allowed us to determine the value of the theoretical limiting molar conductivity (Λm0) of the studied complexes, the values of the inclusion complex formation constants (Kf) and the values of thermodynamic functions (ΔG0, ΔH0 and ΔS0) describing the complexation process in the studied temperature range.
| S-EPMC10095696 | biostudies-literature