Spectroscopic,quantum computational and molecular docking studies on 1-phenylcyclopentane carboxylic acid

The vibrational wavenumbers of optimized molecular structure of 1-phenylcyclopentane carboxylic acid (1PCPCA) molecule have been calculated by quantum chemical theory and compared with experimental results. The density functional theory (DFT) approach is followed using the method B3LYP and 6-311++G(d,p) basis set. Using potential energy distribution, all the assignments of the basic vibrational modes were calculated. Natural bond orbital (NBO) and atoms in molecules (AIM) topological studies applied to get the intermolecular interactions of the compound. ¹H and ¹³C chemical shift of NMR was estimated on the molecule and also compared with the experimental spectra. In order to find the band gap, the time-dependent (TD-DFT) method is used to get the higher order energy levels properties and also compared with experimental data of UV–vis spectrum. From the analysis of various spectroscopic studies, there is a good relationship between the experimental and theoretical values obtained. Quantum characters, bio-active nature and reactive areas of the molecule are revealed by Fukui function, molecular electrostatic potential (MEP) and Hirshfeld surface studies. The human enzyme steroidogenic types and their protein targets were tested with this molecule by molecular docking.     

Synthesis,characterization, computational,excited state properties,wave function and molecular docking studies of (E)-1-(perfluorophenyl)-N-(p-tolyl) methanimine

The compound (E)-1-(perfluorophenyl)-N-(p-tolyl)methanimine (PFPT) was synthesized and characterized by the Infrared, UV–Visible, and NMR analysis. Using density functional theory, the current work is a set of theoretical studies on PFPT. The compound molecular structure and geometry were defined using DFT. Topological studies, like electron localized function, localized orbital locator, average localized ionization energy, and reduced density gradient studies, were done with the Multiwfn-3.8 to find the main binding areas and weak interactions in the molecule. Using the IEFPCM solvation model used to study the calculated UV–Visible spectrum, we used two different solvents. The HOMO-LUMO, MEP, and NLO properties were carried out by DFT/B3LYP/cc-pVDZ in the gas phase. The NBO calculations are used to study how charges move between and within the molecule and the stability of this molecule. A pharmacological analysis is done using an online tool like Swiss-ADME, to see if the molecule could be a potential drug candidate; this evaluation looks at the drug-likeness, ADME, and eco-friendly toxicity properties of the PFPT molecule. Auto-dock suite and Discovery studio Visualizer are used to do molecular docking against 2QFA protein.     

3D-QSAR,docking, molecular dynamics simulation and free energy calculation studies of some pyrimidine derivatives as novel JAK3 inhibitors

Janus kinase 3 (JAK3) is a promising drug target for the treatment of inflammatory diseases, autoimmune disorders, organ transplant rejection and various cancers. In the present study, 3D-QSAR, docking, MD simulation and MM/PBSA studies were performed on a series of pyrimidine-based JAK3 inhibitors. A reliable COMSIA (q² = 0.717 and r² = 0.986) model was developed and validated using external validation test set, bootstrapping, progressive scrambling and r_m² metrics analyses. Structural requirements identified through contour maps of the model were strategically utilized to computationally design 170 novel JAK3 inhibitors with improved potency. Docking studies were performed on the selected data set and newly designed compounds to show their binding mode and to identify important interacting residues inside the active site of JAK3. In addition, docking results of the selected designed compounds inside the active sites of JAK1, JAK2 and TYK2 indicated their JAK3 selectivity. MD simulation (100 ns) on the docked complex of compound 28 (one of highly active compounds of the data set) assisted in the further exploration of the binding interactions. Some crucial residues like Lys830 (glycine-rich loop), Val836, Ala853, Leu905 (hinge region), Cys909, Asn954, Leu956 and Ala966 were identified. Hydrogen bond interactions with hinge residue Leu905 were critical for the binding of JAK3 inhibitors. Additionally, MM/PBSA calculation provided the binding free energy of the compound 28. Newly designed molecules showed promising results in the preliminary in silico ADMET evaluations. Outcomes of the study can further be exploited to develop potent JAK3 inhibitors.     

Quantum computational,spectroscopic and molecular docking studies on 6-amino-3-bromo-2-methylpyridine

In order to confirm the vibrational assignments, the density functional hypothesis has been used for 6-amino-3-bromo-2-methylpyridine (6A3B2MP). The entire energy distribution is used to materialize the several vibrational modes of 6A3B2MP (TED). The DFT/B3LYP approach is used to examine the molecular optimum limits and electronic characteristics of 6A3B2MP. Investigations have been made into the molecular orbital, Fukui function analysis, natural bond orbital (NBO), and molecular electrostatic potential (MEP) characteristics of 6A3B2MP. Theoretical studies have focused on the UV–vis spectra with different solvents. According to the outcomes of the molecular docking technique, the 6A3B2MP is docked with two target proteins, which is crucial for the emergence of cancer. Therefore, this research paves the door for the development of medicines that are specially formulated.     

Synthesis,computational, molecular docking studies and photophysical properties of (Z)-N-(pyrimidin-2-yl)-4-(thiophen-2-ylmethylene)amino) benzenesulfonamide

The (Z)-N-(pyrimidin-2-yl)-4-(thiophen-2-ylmethylene)amino) benzenesulfonamide (TH2DA) were synthesized and characterized by the Infrared, UV–Visible, and NMR analysis. Using density functional theory, the current work is a set of theoretical studies on TH2DA. The compound molecular structure and geometry were defined using DFT. Topological studies, like ELF, LOL, ALIE, and RDG studies, were done with the Multiwfn-3.8 to find the main binding areas and weak interactions in the molecule. Using the IEFPCM solvation model were used to study the calculated UV–Visible spectrum. The HOMO-LUMO, MEP, and NLO properties were carried out in the gas phase. The NBO calculations are used to study how charges move between and within the molecule and stability of this molecule. A pharmacological analysis is done using online tool like Swiss-ADME, to see if the molecule could be potential drug candidate; this evaluation looks at the drug-likeness, ADME and eco-friendly toxicity properties of the TH2DA molecule. Auto-dock suite and Discovery studio Visualizer are used to do molecular docking studies.     

Isolation,vibrational analysis,quantum chemical studies,nature of bonding,and molecular docking studies of triterpenoid isolates from Ganoderma lucidum as potent typhoid fever agent

The bacteria Salmonella Typhi is the source of the dangerous and perhaps fatal disease known as typhoid fever. Typhoid fever treatment is difficult despite the availability of potent medications due to the rise of multi-drug resistance strains. Herein, the extraction, LC-MS and FT-IR spectral characterization, density functional theory (DFT) and molecular docking investigation of 3,15-dihydroxy-11-toxolanost-8,24-dien-26-oic acid (C₃₀H₄₅O₅) [MDC_1], Ganoderic acid F (C₃₂H₄₁O₉) [MDC_2], and Ganolucidic acid E (C₃₀H₄₃O₅) [MDC_3] isolated compounds from G. lucium against Salmonella Typhi enzyme, DNA gyrase B is presented along with the influence of solvation in polar and non-polar solvents. The FT-IR spectral results show that the triterpenoid extract of G. lucidum contains oxygen atoms, which mainly exist in functional groups (such as CO, O–H, C–O) and are consistent with the general molecular structures of triterpenoids. The reactivity parameters in the gas phase show that MDC_1 and MDC_3 have higher energy gaps whereas MD_2 has the lowest energy gap, indicating that it is more reactive than the other complexes. The energy gap of the compounds in solvent also shows a little shift, compared to the energy gap in Ethanol and Heptane, respectively. The results of the molecular docking study revealed several small molecules with strong binding affinities for the protein targets, suggesting that they could be used as potential therapeutics for typhoid fever. Therefore, this study suggests that molecular docking is a powerful tool for identifying novel therapeutics against tropical diseases such as typhoid fever.     

Design,molecular docking analysis of an anti-inflammatory drug,computational analysis and intermolecular interactions energy studies of 1-benzothiophene-2-carboxylic acid

In this paper, theoretical study on molecular geometry, vibrational, pharmaceutical and electronic properties of the monomeric and dimeric structures of 1-benzothiophene-2-carboxylic acid (2BT) were carried out using B3LYP hybrid functional with 6-311++G(d,p) as basis set. The structural study show that the stability of 2BT crystalline structure arising from O-H…O, C-H…O as well as S-H…O hydrogen bonding interactions. Vibrational analysis, for monomer and dimer species, show a good compatibility between experimental and theoretical frequencies. Then, the 1H and 13C NMR chemical shifts were calculated using Gauge Independent Atomic Orbital (GIAO) technical. In addition, the UV-Vis spectrum was simulated in gas phase and in water throughout TD-DFT calculation. The electronic transitions were identified based on HOM-LUMO energies. However, donor-acceptor interactions and charge delocalization has been studied via natural bond orbital (NBO). The nucleophilic and electrophilic site localization is identified by molecular electrostatic potential. Hirshfeld surface analysis has been discussed based on color code demonstrating the various non covalent interactions. Besides, molecular docking analysis was reported to evince the pharmaceutical properties of the studied molecule.     

Conformers,properties, and docking mechanism of the anticancer drug docetaxel: DFT and molecular dynamics studies

The conformational structures and properties of the anticancer drug docetaxel (DTX) are studied theoretically. A total of 3888 trial structures were initially generated by all combinations of internal single‐bond rotamers and screened with the B3LYP/3‐21G* method. A total of 31 unique conformers were further optimized at the B3LYP/6‐311G* method. Their relative energies, dipole moments, rotational constants, and harmonic vibrational frequencies were predicted. Single‐point relative energies were then determined at the M06‐L/6‐311G(2df,p) level. The UV spectrum of the lowest‐lying DTX conformer in methanol was investigated with the TD‐CAM‐B3LYP/6‐311 + G(2df,p) method. The 31 unique DTX structures are mainly docked at three different sites within β‐tubulin. Based on the results of molecular docking and double‐float MD simulations, the lowest‐lying DTX conformer consistently exhibits good docking performance with β‐tubulin. We identified the residues LYS299, ARG215, GLN294, LEU275, THR216, GLU290, PRO274, and THR276 on β‐tubulin as active sites forming a binding pocket responsible for locking DTX within β‐tubulin to make the combination more stable. The RMSD values show that the predicted complexes are favorable, and the SASA analysis shows that the hydrophilic properties of DTX are better than paclitaxel. © 2018 Wiley Periodicals, Inc.     

Recent studies of docking and molecular dynamics simulation for liquid‐phase enantioseparations

Liquid‐phase enantioseparations have been fruitfully applied in several fields of science. Various applications along with technical and theoretical advancements contributed to increase significantly the knowledge in this area. Nowadays, chromatographic techniques, in particular HPLC on chiral stationary phase, are considered as mature technologies. In the last thirty years, CE has been also recognized as one of the most versatile technique for analytical scale separation of enantiomers. Despite the huge number of papers published in these fields, understanding mechanistic details of the stereoselective interaction between selector and selectand is still an open issue, in particular for high‐molecular weight chiral selectors like polysaccharide derivatives. With the ever growing improvement of computer facilities, hardware and software, computational techniques have become a basic tool in enantioseparation science. In this field, molecular docking and dynamics simulations proved to be extremely adaptable to model and visualize at molecular level the spatial proximity of interacting molecules in order to predict retention, selectivity, enantiomer elution order, and profile noncovalent interaction patterns underlying the recognition process. On this basis, topics and trends in using docking and molecular dynamics as theoretical complement of experimental LC and CE chiral separations are described herein. The basic concepts of these computational strategies and seminal studies performed over time are presented, with a specific focus on literature published between 2015 and November 2018. A systematic compilation of all published literature has not been attempted.     

Computational study of new 1,2,3-triazole derivative of lithocholic acid: Structural aspects,non-linear optical properties and molecular docking studies as potential PTP 1B enzyme inhibitor

We have reported synthesis of a novel 1,2,3-triazole conjugate of lithocholic acid by 1,3-dipolar cycloaddition reaction. The molecular properties such as geometry, conformations, bond lengths and dihedral angles were investigated theoretically. The bond order analysis was performed using Wiberg bond order (WBO), Fuzzy bond order (FBO) and Laplacian bond order (MBO) method. Electronic properties of molecule such as electrostatic surface potential analysis, frontier molecular orbital analysis, reduced density gradient, total density of states, and global chemical reactivity indices have been investigated. The nonlinear optical properties were also investigated. Total dipole moment, mean polarizability and hyperpolarizability were found to be much higher than standard urea molecule which suggests that it could act as potential NLO material. The molecular docking calculations are also performed to investigate its potential as PTP 1B enzyme inhibitor.     

Spectroscopic,quantum chemical,ADMET and molecular docking studies of echinatin: a prospective tuberculosis drug

Research on Chemical Intermediates - Tuberculosis (TB) is a potentially fatal infectious illness affecting mostly the lungs. Tuberculosis bacteria are communicated from person to person via minute...     

Synthesis,cytotoxicity, apoptosis and molecular docking studies of novel phenylbutyrate derivatives as potential anticancer agents

Phenylbutyrate (PB), a small aromatic fatty acid, has been known as an interesting compound with the ability of anti-proliferation and cell growth inhibition in cancer cells. In the present study, a series of PB derivatives were synthesized by Passerini multicomponent reaction and their cytotoxic activities against various human cancer cell lines including A549 (non-small cell lung cancer), MDA-MB-231 (breast cancer), and SW1116 (colon cancer) were evaluated. The results revealed that B9, displayed significantly higher in vitro cytotoxicity with IC₅₀ of 6.65, 8.44 and 24.71 μM, against A549, MDA-MB-231 and, SW1116, respectively, in comparison to PB. The effects of these compounds on the proliferation of MCF-10A as non-tumoral breast cell line, showed good selectivity of the compounds between tumorigenic and non-tumorigenic cell lines. Moreover, B9 has indicated apoptosis-inducing activities to MDA-MB-231 cancer cell line in a dose-dependent manner. The molecular docking studies of the synthesized compounds on pyruvate dehydrogenase kinase 2 (PDK2; PDB ID: 2BU8) and histone deacetylase complex (HDAC; PDB ID: 1C3R), as the main targets of PB were applied to predict the binding sites and binding orientation of the compounds to these targets.     

Molecular structural investigations of quinoxaline derivatives through 3D-QSAR,molecular docking,ADME prediction and pharmacophore modeling studies for the search of novel antimalarial agent

In the present article, a dataset of 63 quinoxaline derivatives were taken for antimalarial activity and pharmacophore were developed. Atom based method was used to develop a three dimensional quantitative structure activity relationship (3D-QSAR) model. On comparison of all statistical parameters, model AHRRR23 was found to be the most effective and predictive QSAR model as it satisfied all statistical parameters of a good model. The model AHRRR23 showed an adequate R² value for the training set 0.9446, good predictive power with Q² of 0.6409, good F- value, low SD 0.1218 value and outstanding Pearson-R values and low RMSE 0.2779 values of the model. The docking studies also gives very good results with good RMSD values. 3D QSAR, docking and ADME studies exhibits that the developed model could be employed as a potential lead for further study as antimalarial drug.     

Computational study of 3-thiophene acetic acid: Molecular docking,electronic and intermolecular interactions investigations

The present work undertakes the structural and electronic properties of 3-thiophene acetic acid (abbreviated as 3-TAA) monomer and dimer. DFT calculations were performed using B3LYP functional in combination with the aug-cc-pVTZ basis set. The optimized structural parameters were found to be in a good agreement with experimental molecular geometry. The stability of the crystal packing was ensured by OH⋯O, C-H⋯O and CH⋯S intermolecular interactions. All the Non covalent interactions were deeply studied in terms of their topological parameters, Hirshfeld surface (HS) analysis and reduced density gradient (RDG) analysis. The electronic properties of the investigated compound have been performed using time dependent density functional theory (TD-DFT) and discussed through its correspondant HOMO, LUMO and excitation energy values. Likewise, the reactivity of 3-TAA was discussed in terms of several thermodynamic parameters. In addition, the molecular electrostatic potential (MEP) surface has been performed and discussed in terms of color distribution. In addition, the natural bond orbital (NBO) analysis was used to investigate the electronic charge transfer into the molecule. Harmine, Clorgyline, Isatin, zonisamide and our title compound including are known with their competitive inhibitory activity on Human monoamine oxidase, commonly named MAO A and B. This enzyme is a critical enzyme in the degradative deamination of biogenic amines throughout the body. Thus, molecular docking behaviors of 3-TAA are computed and compared to the results found for Harmine, Clorgyline, Isatin, zonisamide ligands.     

Homology modelling and molecular docking studies of human placental cadherin protein for its role in teratogenic effects of anti-epileptic drugs

Anti-epileptic drugs (AEDs) have high risk of teratogenic side effects, including neural tube defects while mother is on AEDs for her own prevention of convulsions during pregnancy. The present study investigated the interaction of major marketed AEDs and human placental (hp)-cadherin protein, in-silico, to establish the role of hp-cadherin protein in teratogenicity and also to evaluate the importance of Ca²⁺ ion in functioning of the protein. A set of 21 major marketed AEDs were selected for the study and 3D-structure of hp-cadherin was constructed using homology modelling and energy minimized using MD simulations. Molecular docking studies were carried out using selected AEDs as ligand with hp-cadherin (free and bound Ca²⁺ ion) to study the behavioural changes in hp-cadherin due to presence of Ca²⁺ ion. The study reflected that four AEDs (Gabapentin, Pregabalin, Remacimide and Vigabatrine) had very high affinity towards hp-cadherin and thus the later may have prominent role in the teratogenic effects of these AEDs. From docking simulation analysis it was observed that Ca²⁺ ion is required to make hp-cadherin energetically favourable and sterically functional.