scholarly journals Deciphering the Relationship Between Cycloheximides Structures and Their Different Biological Activities

2021 ◽  
Vol 12 ◽  
Author(s):  
Hang Thi Thu Nguyen ◽  
Jae Deok Kim ◽  
Vinit Raj ◽  
In Min Hwang ◽  
Nan Hee Yu ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Molecular Docking ◽  
Density Functional ◽  
Computational Study ◽  
Fermentation Broth ◽  
Biological Activities ◽  
Pythium Ultimum ◽  
Binding Energies ◽  
Dependent Manner ◽  
Inhibitory Activities

Streptomyces species are the most important sources of antibacterial, antifungal, and phytotoxic metabolites. In this study, cycloheximide (CH) and acetoxycycloheximide (ACH) were isolated from the fermentation broth of Streptomyces sp. JCK-6092. The antifungal and phytotoxic activities of the two compounds (CH and ACH) and a cycloheximide derivative, hydroxycycloheximide (HCH), were compared. CH exhibited the strongest antagonistic activity against all the true fungi tested, followed by ACH and HCH. However, both CH and ACH displayed similar mycelial growth inhibitory activities against several phytopathogenic oomycetes, and both were more active than that of HCH. Disparate to antifungal ability, ACH showed the strongest phytotoxic activity against weeds and crops, followed by HCH and CH. ACH caused chlorophyll content loss, leaf electrolytic leakage, and lipid peroxidation in a dose-dependent manner. Its phytotoxicity was stronger than that of glufosinate-ammonium but weaker than that of paraquat in the in vitro experiments. CH and its derivatives are well-known protein synthesis inhibitors; however, the precise differences between their mechanism of action remain undiscovered. A computational study revealed effects of CHs on the protein synthesis of Pythium ultimum (oomycetes), Magnaporthe oryzae (true fungus), and Capsicum annum (plant) and deciphered the differences in their biological activities on different targets. The binding energies and conformation stabilities of each chemical molecule correlated with their biological activities. Thus, molecular docking study supported the experimental results. This is the first comparative study to suggest the ribosomal protein alteration mechanisms of CHs in plants and fungi and to thus show how the protein inhibitory activities of the different derivatives are altered using molecular docking. The correlation of structures features of CHs in respect to bond formation with desired protein was revealed by density functional theory. Overall collective results suggested that CHs can be used as lead molecules in the development of more potent fungicides and herbicides molecules.

scholarly journals Combinatorial Library Designing and Virtual Screening of Cryptolepine Derivatives against Topoisomerase II by Molecular Docking

2020 ◽  
Author(s):  
Maria ◽  
Zahid Khan
Keyword(s):  
Molecular Docking ◽  
Cell Division ◽  
Binding Energy ◽  
Cancer Cells ◽  
Anticancer Agents ◽  
Combinatorial Library ◽  
Topoisomerase Ii ◽  
Computational Study ◽  
Binding Energies ◽  
Potential Inhibitors

AbstractComputational approaches have emerging role for designing potential inhibitors against topoisomerase 2 for treatment of cancer. TOP2A plays a key role in DNA replication before cell division and thus facilitates the growth of cells. This function of TOP2A can be suppressed by targeting with potential inhibitors in cancer cells to stop the uncontrolled cell division. Among potential inhibitors cryptolepine is more selective and has the ability to intercalate into DNA, effectively block TOP2A and cease cell division in cancer cells. However, cryptolepine is non-specific and have low affinity, therefore, a combinatorial library was designed and virtually screened for identification of its derivatives with greater TOP2A binding affinities.A combinatorial library of 31114 derivatives of cryptolepine was formed and the library was virtually screened by molecular docking to predict the molecular interactions between cryptolepine derivatives and TOP2A taking cryptolepine as standard. The overall screening and docking approach explored all the binding poses of cryptolepine for TOP2A to calculate binding energy. The compounds are given database number 8618, 907, 147, 16755, and 8186 scored lowest binding energies of −9.88kcal/mol, −9.76kcal/mol, −9.75kcal/mol, −9.73kcal/mol, and −9.72kcal/mol respectively and highest binding affinity while cryptolepine binding energy is −6.09kcal/mol. The good binding interactions of the derivatives showed that they can be used as potent TOP2A inhibitors and act as more effective anticancer agents than cryptolepine itself. The interactions of derivatives with different amino acid residues were also observed. A comprehensive understanding of the interactions of proposed derivatives with TOP2A helped for searching more novel and potent drug-like molecules for anticancer therapy. This Computational study suggests useful references to understand inhibition mechanisms that will help in the modification of TOP2A inhibitors.

Computational study of Mg insertion into amorphous silicon: advantageous energetics over crystalline silicon for Mg storage

2013 ◽  
Vol 1540 ◽  
Author(s):  
Fleur Legrain ◽  
Oleksandr I. Malyi ◽  
Teck L. Tan ◽  
Sergei Manzhos
Keyword(s):  
Density Functional ◽  
Nearest Neighbor ◽  
Defect Formation ◽  
Crystalline Silicon ◽  
Computational Study ◽  
Binding Energies ◽  
Functional Theory ◽  
Wide Range ◽  
Insertion Sites ◽  
Formation Energies

ABSTRACTWe show in a theoretical density functional theory study that amorphous Si (a-Si) has more favorable energetics for Mg storage compared to crystalline Si (c-Si). Specifically, Mg and Li insertion is compared in a model a-Si simulation cell. Multiple sites for Mg insertion with a wide range of binding energies are identified. For many sites, Mg defect formation energies are negative, whereas they are positive in c-Si. Moreover, while clustering in c-Si destabilizes the insertion sites (by about 0.1/0.2 eV per atom for nearest-neighbor Li/Mg), it is found to stabilize some of the insertion sites for both Li (by up to 0.27 eV) and Mg (by up to 0.35 eV) in a-Si. This could have significant implications on the performance of Si anodes in Mg batteries.

Computational study on transfer of L-ascorbic acid by UlaA throughEscherichia colimembrane

2017 ◽  
Vol 15 (03) ◽  
pp. 1750007 ◽  
Author(s):  
Ehsan Faghih-Mirzaee ◽  
Maryam Dehestani ◽  
Leila Zeidabadinejad
Keyword(s):  
Ascorbic Acid ◽  
Molecular Docking ◽  
Active Sites ◽  
Density Functional ◽  
Md Simulation ◽  
Computational Study ◽  
Radius Of Gyration ◽  
Internal Cavity ◽  
Chemical Hardness ◽  
E Coli

In this study, the transfer of L-ascorbic acid by UlaA through Escherichia coli (E. coli) membrane was evaluated using density functional theory (DFT), molecular docking, and molecular dynamics (MD) simulation methods. DFT calculations at the B3lyp/6[Formula: see text]311[Formula: see text]G(p,d) level were performed to investigate the interaction properties and molecular descriptors. The physical properties, such as chemical potential, chemical hardness, and chemical electrophilicity of all studied molecules, were investigated. Natural population analysis was employed to describe the state of charge transfer between interactions using the natural bond orbital (NBO). The atoms in molecules (AIM) theory was used to examine the properties of the bond critical points such as their electron densities and Laplacians. Molecular docking studies showed that L-ascorbic acid was bounded to the internal cavity of UlaA. It was found that there were some hydrogen bond interactions between L-ascorbic acid and active sites of UlaA. The results of the MD simulation showed that the root mean square deviation (RMSD) of UlaA and L-ascorbic acid bound-UlaA reached equilibrium after 3.7[Formula: see text]ns. An evaluation of the radius of gyration ([Formula: see text]) revealed that UlaA and L-ascorbic acid bound-UlaA were stabilized around 10,000[Formula: see text]ns. Finally, analysis of the RMS fluctuations suggested that the structure of the L-ascorbic acid binding site remained approximately rigid during simulation. All obtained results shed light on the special manner of L-ascorbic acid transfer through E. coli membrane, and confirmed the results of previous studies on this issue.

scholarly journals Computer-Based Approaches for Determining the Pharmacological Profile of 5-(3-Nitro-Arylidene)-Thiazolidine-2,4-Dione

2021 ◽  
Vol 11 (6) ◽  
pp. 13806-13828
Keyword(s):  
Molecular Docking ◽  
In Silico ◽  
Density Functional ◽  
Biological Activities ◽  
Computational Approach ◽  
Basis Set ◽  
Pharmacological Profile ◽  
Dft Methods ◽  
Starting Point ◽  
In Silico Studies

The development of novel and safe compounds is a challenging task in the drug discovery trajectory. Accordingly, the individuation of promising core molecules with biological activities could pave the way to develop effective drugs to treat a given disease. The use of a computational approach can reduce the time for identifying promising core molecules characterizing their potential pharmacological profile and providing hints for the synthesis of novel derivatives with increased predicted pharmacological activity. Following this strategy, starting from a core molecule thiazolidine-2,4-dione, the derivative of 5-(3-nitro-arylidene)-thiazolidine-2,4-dione was synthesized to investigate the biological and pharmacological potential. An extensive computational investigation was performed employing ab initio calculations by using Density Functional Theory (DFT), and subsequent in silico studies were accomplished by molecular docking calculation. The structures 5-(3-nitro-arylidene)-thiazolidine-2,4-dione were fully optimized using multiparametric DFT methods were calculated at the B3LYP/6-31+G (d, p) level basis set. Besides gaining insights into the potential pharmacological profile of the selected derivative, molecular docking against some selected drug targets, ADME, and PASS prediction were performed. According to charges and molecular electrostatic potential (MESP) calculation, the N-H region could offer promising active site interactions for protein binding. Furthermore, Homo-Lumo and global reactivity values indicate a good profile for the selected compound, and UV-Vis provides further insights about its properties, potentially helpful for further experimental analysis. Notably, the in silico investigation indicated that EGFR and ORF2 enzymes could represent the selected drug-like compound's possible targets. Conclusively, the proposed computational approach demonstrated that it is possible to evaluate a proposed compound's bioactivity profile. We characterized 5-(3-nitro-arylidene)-thiazolidine-2,4-dione derivative, suggesting it as a good starting point for developing interesting hit compounds with a relevant pharmacological profile.

scholarly journals Water Interaction with Fe2NiP Schreibersite (110) Surface: a Quantum Mechanical Atomistic Perspective

2022 ◽  
Author(s):  
Stefano Pantaleone ◽  
Marta Corno ◽  
Albert Rimola ◽  
Nadia Balucani ◽  
Piero Ugliengo
Keyword(s):  
Density Functional ◽  
Biological Activities ◽  
Binding Energies ◽  
Phosphorus Compounds ◽  
Functional Theory ◽  
Water Binding ◽  
Specific Element ◽  
Empirical Correction ◽  
Open Questions ◽  
Wetting Process

Phosphorus is an element of primary importance for all living creatures, being present in many biological activities in the form of phosphate (PO43-). However, there are still open questions about the origin of this specific element and on the transformation which allowed it to be incorporated in biological systems. The most probable source of prebiotic phosphorus is the intense meteoritic bombardment during the Archean era, few million years after the solar system formation, which brought tons of iron-phosphide materials (schreibersite) on the early Earth crust. It was recently demonstrated that by simple wetting/corrosion processes from this material various oxygenated phosphorus compounds are produced. In the present work, the wetting process of schreibersite (Fe2NiP) was studied by computer simulations using density functional theory, with the PBE functional supplemented with dispersive interactions through a posteriori empirical correction. To start disentangling the complexity of the system, only the most stable (110) surface of Fe2NiP was used simulating different water coverages, from which structures, water binding energies and vibrational spectra have been predicted. The computed (ana-)harmonic infrared spectra have been compared with the experimental ones, thus confirming the validity of the adopted methodology and models.

scholarly journals Design, Synthesis, and Evaluation of X-ray Crystal Structure, Biological Activities, DFT Calculations, and Molecular Docking of Phenyl Imidazolidin-2-One Derivatives

Crystals ◽  
2020 ◽  
Vol 10 (8) ◽  
pp. 713
Author(s):  
Xile Deng ◽  
Can Jin ◽  
Yong Xie ◽  
Junbo Gao ◽  
Xiaomao Zhou
Keyword(s):  
Molecular Docking ◽  
Dft Calculations ◽  
Insecticidal Activity ◽  
Plutella Xylostella ◽  
Density Functional ◽  
Biological Activities ◽  
Phytophthora Sojae ◽  
Ring Closure ◽  
Binding Modes ◽  
X Ray

Eight phenyl imidazolinone derivatives were synthesized from N2-(2,4-dimethylphenyl)-N1-methyformamidine (DPMF) via scaffold-hopping method using the ring-closure approach. The prepared compounds were verified using 1H and 13C NMR and HRMS spectroscopies. The structure of compound 3c was confirmed by single-crystal X-ray diffraction analysis. The mean plane of the phenyl and imidazolinone moieties was almost coplanar with an angle of 8.85(4)°. In the crystal, molecules were interlinked with intermolecular hydrogen bonds (N–H···O and C–H···O), generating a network structure. Additionally, compound 3f displayed the highest insecticidal activity (86.7%) against Plutella xylostella at 600 mg/L, which was significantly higher than the insecticidal activity (23.0%) of DPMF. Also, compound 3d displayed good fungicidal activities against Phytophthora capsici, Phytophthora sojae, and Phytophthora infestans. Density functional theory (DFT) calculations were performed to explain the insecticidal and fungicidal activities of phenyl imidazolidin-2-one derivatives, especially potent compounds 3f and 3d. Moreover, the binding modes of compounds 3a–h and DPMF against octopamine receptor of Plutella xylostella were studied by homology modeling and molecular docking. Therefore, a preliminary structure–activity relationship (SAR) was derived and discussed. These results encourage the exploration of novel insecticides and fungicides based on DPMF.

scholarly journals Anion Recognition by Neutral and Cationic Iodotriazole Halogen Bonding Scaffolds

Molecules ◽  
2020 ◽  
Vol 25 (4) ◽  
pp. 798
Author(s):  
Iñigo Iribarren ◽  
Goar Sánchez-Sanz ◽  
Cristina Trujillo
Keyword(s):  
Density Functional ◽  
Computational Study ◽  
Halogen Bond ◽  
Anion Recognition ◽  
Lone Pair ◽  
Halogen Bonding ◽  
Binding Energies ◽  
Bond Critical Point ◽  
Density Values ◽  
Intramolecular Hydrogen

A computational study of the iodide discrimination by different neutral and cationic iodotriazole halogen bonding hosts was carried out by means of Density Functional Theory. The importance of the size of the scaffold was highlighted and its impact observed in the binding energies and intermolecular X⋯I distances. Larger scaffolds were found to reduce the electronic repulsion and increase the overlap between the halide electron lone pair and the corresponding I-C antibonding orbital, increasing the halogen bonding interactions. Additionally, the planarity plays an important role within the interaction, and can be tuned using hydroxyl to perform intramolecular hydrogen bonds (IMHB) between the scaffold and the halogen atoms. Structures with IMHB exhibit stronger halogen bond interactions, as evidenced by the shorter intramolecular distances, larger electron density values at the bond critical point and more negative binding energies.

scholarly journals Chemical Profiles and Pharmacological Properties with in Silico Studies on Elatostema papillosum Wedd

Molecules ◽  
2021 ◽  
Vol 26 (4) ◽  
pp. 809 ◽  
Author(s):  
Md. Zia Uddin ◽  
Arkajyoti Paul ◽  
Ahmed Rakib ◽  
Saad Ahmed Sami ◽  
Shafi Mahmud ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Binding Affinity ◽  
Serotonin Receptor ◽  
Computational Study ◽  
Biological Activities ◽  
Binding Affinities ◽  
In Silico Studies ◽  
Cox 2 ◽  
Cox 1

The current study attempted, for the first time, to qualitatively and quantitatively determine the phytochemical components of Elatostema papillosum methanol extract and their biological activities. The present study represents an effort to correlate our previously reported biological activities with a computational study, including molecular docking, and ADME/T (absorption, distribution, metabolism, and excretion/toxicity) analyses, to identify the phytochemicals that are potentially responsible for the antioxidant, antidepressant, anxiolytic, analgesic, and anti-inflammatory activities of this plant. In the gas chromatography-mass spectroscopy analysis, a total of 24 compounds were identified, seven of which were documented as being bioactive based on their binding affinities. These seven were subjected to molecular docking studies that were correlated with the pharmacological outcomes. Additionally, the ADME/T properties of these compounds were evaluated to determine their drug-like properties and toxicity levels. The seven selected, isolated compounds displayed favorable binding affinities to potassium channels, human serotonin receptor, cyclooxygenase-1 (COX-1), COX-2, nuclear factor (NF)-κB, and human peroxiredoxin 5 receptor proteins. Phytol acetate, and terpene compounds identified in E. papillosum displayed strong predictive binding affinities towards the human serotonin receptor. Furthermore, 3-trifluoroacetoxypentadecane showed a significant binding affinity for the KcsA potassium channel. Eicosanal showed the highest predicted binding affinity towards the human peroxiredoxin 5 receptor. All of these findings support the observed in vivo antidepressant and anxiolytic effects and the in vitro antioxidant effects observed for this extract. The identified compounds from E. papillosum showed the lowest binding affinities towards COX-1, COX-2, and NF-κB receptors, which indicated the inconsequential impacts of this extract against the activities of these three proteins. Overall, E. papillosum appears to be bioactive and could represent a potential source for the development of alternative medicines; however, further analytical experiments remain necessary.

scholarly journals Cruzain Inhibition by Terpenoids: A Molecular Docking Analysis

2008 ◽  
Vol 3 (6) ◽  
pp. 1934578X0800300 ◽  
Author(s):  
Ifedayo V. Ogungbe ◽  
William N. Setzer
Keyword(s):  
Molecular Docking ◽  
Active Site ◽  
Binding Energies ◽  
Hydrophobic Pocket ◽  
Docking Analysis ◽  
Protein Target ◽  
Hydrophobic Compounds ◽  
Sesquiterpene Hydrocarbons ◽  
Inhibitory Activities ◽  
Molecular Docking Analysis

A molecular docking analysis has been carried out using monoterpene and sesquiterpene hydrocarbons and triterpenoids that have shown enzyme inhibitory activity as ligands for the cysteine protease cruzain. The binding energies of the docked ligands roughly correlate with their inhibitory activities. The orientations of the docked ligands are consistent with a mechanism whereby these hydrophobic compounds dock into a hydrophobic pocket near the active site, thereby blocking binding of the protein target to the protease.

DFT Study of Efinaconazole, an Antifungal Drug and Its Molecular Docking against a Holoenzyme (pdb id: 3IDB)

2021 ◽  
Vol 13 (2) ◽  
pp. 679-694
Author(s):  
J. Hossen ◽  
T. K. Pal
Keyword(s):  
Molecular Docking ◽  
Hydrogen Bonds ◽  
Density Functional ◽  
Computational Study ◽  
Antifungal Drug ◽  
Internal Displacement ◽  
Chemical Hardness ◽  
Discovery Studio ◽  
Non Covalent Interactions ◽  
Covalent Interactions

Efinaconazole (ECZ) is an antifungal drug. Various non-covalent interactions between ECZ and a holoenzyme (protein id: 3idb) has been investigated through computational study. The structure of ECZ was optimized using density functional theory (DFT) applying B3LYP/6-311G+(d,p) method. HOMO, LUMO, chemical hardness and softness, several thermochemical parameters, electrostatic potential surface, vibrational spectrum, total energy, and maximum internal force and maximum internal displacement with respect to optimization step number have been determined. The optimized ECZ ligand was subjected to molecular docking against the protein 3idb in Autodock Vina program. The different non-covalent interactions in the ligand-protein complex were visualized in BIOVIA Discovery Studio Visualizer. Various surface plots such as hydrogen bonds, ionizability, SAS, hydrophobicity, aromatic and charge surfaces were excerpted. ECZ molecule forms three strong hydrogen bonds with amino acid residues of the holoenzyme. In addition to this, it is significantly capable to form several other bonds which strengthen the ligand-protein interaction. The result showed that the ECZ molecule posed considerable binding affinity against the macromolecule.

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