Novel ibuprofen prodrug: A possible promising agent for the management of complications of Alzheimer's disease.

Background: Alzheimer's disease (AD) is a severe, varied, and complex brain condition that gradually impairs memory and cognitive function. Epidemiological studies have shown that patients who have a history of long-term NSAID use have a decreased risk of developing AD. The objective of this study is to conduct the structural analysis of a novel ibuprofen prodrug and test its anti-Alzheimer's properties. Methods: Computational and docking studies were conducted using AMBER 18 package. The in-vivo studies were performed using aluminum chloride-induced experimental AD in rats. Adult Wistar rats of either sex were used and treated with aluminum chloride (32.5 mg/kg, p.o) and ibuprofen prodrug (50 mg/kg, p.o) daily for 30 days. The hole-board test and elevated plus maze were conducted on 10th, 20th and 30th day. Further, on 31st day, animals were euthanized and the brain tissue was used for histopathology. The results obtained were subjected to statistical analysis by one-way ANOVA and Dunnet's test, p < 0.05 was considered to indicate the significance. Results: The structural configuration of the novel compound indicated the presence of several structures such as aliphatic, aromatic, and asymmetry in the compound. The geometrical analysis indicated that the ibuprofen conjugate has dreiding energy of 51.22 kcal/mol with a van der waals radius of 62.56 A. The Huckel analysis confirmed the presence of aromatic rings in the compound. The molecular docking studies suggested affinity towards beta-secretase and acetylcholinesterase, besides indicating that the compound has ideal characteristics for the oral route (Log P = 2.33), cellular absorption (TPSA = 95.50), and oral bioavailability (number of rotatable bonds = 10). The toxicity profile indicated devoid of major systemic toxicity with mild possibility of cytotoxicity. The in-vivo analysis showed that the Ibu-prodrug significantly (P < 0.001) reversed the changes induced by aluminum chloride and restored histomorphological features in brain tissue. Conclusion: The findings suggested that the ibuprofen conjugate might possess the potential to manage the complications of AD. The action appears to be mediated through inhibition of beta-secretase and acetylcholinesterase activities. More studies might aid in identifying a specific therapeutic intervention that is still lacking in the treatment of AD.

Toxicity, Pharmacokinetic Profile, and Compound-Protein Interaction Study of Polygonum minus Huds Extract.

Several phytochemicals with potential for bioactivity can be found in Polygonum minus (PM). The goal of this investigation was to establish the minimally toxic dose of PM for pharmaceutical use. To explain the stability and reactivity of the compounds under study, the lowest unoccupied molecular orbital (LUMO), the highest occupied molecular orbital (HOMO), and the natural bond orbital were all combined. Additionally, the cytotoxicity of the aqueous and ethanolic extract of PM on the (Hs888Lu) cell line was determined using the MTS Assay Kit (cell proliferation) (colorimetric). The hematological, hepatic, and renal functions were examined during the acute toxicity test on Sprague Dawley rats. SwissADME and ADMET were used to investigate the absorption, distribution, metabolism, excretion, and toxicity (ADMET) of the chemicals isolated from PM, including gallic acid, quercetin, rutin, and coumaric acid (PMCs). Molecular docking was used to examine the inhibitory effect against human H+/K+ ATPase, cyclooxygenase-2, and acetylcholinesterase. The outcomes indicated that neither the aqueous nor the ethanolic extract of PM is harmful. The development of plant-based medicine was made possible by the phenolic chemicals, primarily quercetin and rutin, which exhibit a considerable binding affinity to human H+/K+ ATPase, cyclooxygenase-2, and acetylcholinesterase.

Insights of structure-based pharmacophore studies and inhibitor design against Gal3 receptor through molecular dynamics simulations.

Our present work studies the structure-based pharmacophore modeling and designing inhibitor against Gal3 receptor through molecular dynamics (MD) simulations extensively. Pharmacophore models play a key role in computer-aided drug discovery like in the case of virtual screening of chemical databases, de novo drug design and lead optimization. Structure-based methods for developing pharmacophore models are important, and there have been a number of studies combining such methods with the use of MD simulations to model protein's flexibility. The two potential antagonists SNAP 37889 and SNAP 398299 were docked and simulated for 250 ns and the results are analyzed and carried for the structure-based pharmacophore studies. This helped in identification of the subtype selectivity of the binding sites of the Gal3 receptor. Our work mainly focuses on identifying these binding site residues and to design more potent inhibitors compared to the previously available inhibitors through pharmacophore models. The study provides crucial insight into the binding site residues Ala2, Asp3, Ala4, Gln5, Phe24, Gln79, Ala80, Ile82, Tyr83, Trp88, His99, Ile102, Tyr103, Met106, Tyr157, Tyr161, Pro174, Trp176, Arg181, Ala183, Leu184, Asp185, Thr188, Trp248, His251, His252, Ile255, Leu256, Phe258, Trp259, Tyr270, Arg273, Leu274 and His277, which plays a significant role in the conformational changes of the receptor and helps to understand the inhibition mechanism. Communicated by Ramaswamy H. Sarma.

A theoretical exploration of the intermolecular interactions between resveratrol and water: a DFT and AIM analysis.

The polyphenolic compound resveratrol, classified under stilbenes, offers a broad range of health advantages, including neuroprotection and playing a role in autophagy in the nervous system. However, resveratrol has poor water solubility and is soluble in the gel phase in liposomal membranes. The main aim of this work was to understand the nature of the interactions between resveratrol and water molecules. In the present study, we used the dispersion corrected density functional theory (DFT) method to study hydrogen bonding interactions. Eight different geometries of resveratrol-water complexes were identified by optimizing the geometries by placing water at various locations. We observed the two lowest energy structures to be isoenergetic. In most complexes, water interaction occurs with phenolic hydrogen as all the phenolic hydroxyl groups have identical Vs,max values. Energy decomposition analysis shows that the dispersion contribution was minimal in these complexes, while electrostatic and orbital contributions were larger. Complex formation between water and the resveratrol molecule results in a blue shift in the vibrational frequency, along with an increase in intensity due to the transfer of electron density. The hydrogen bonds in the resveratrol-water complexes have closed-shell interactions with a medium-to-strong bonding nature. Noncovalent index analysis of the complexes shows that, in addition to hydrogen bonding, electrostatic and van der Waal's interactions play a key role in stabilizing the complexes. Graphical abstract Noncovalent index analysis showing that, in addition to hydrogen bonding, electrostatic and van der Waal's interactions play a major role in stabilizing resveratrol-water complexes.

Synthesis of 5-(5-methyl-benzofuran-3-ylmethyl)-3H- [1, 3, 4] oxadiazole-2-thione and investigation of its spectroscopic, reactivity, optoelectronic and drug likeness properties by combined computational and experimental approach.

This paper reports the synthesis of 5-(5-methyl-benzofuran-3-ylmethyl)-3H- [1, 3, 4] oxadiazole-2-thione (5MBOT) and characterization by FT-IR, FT-Raman, 1H NMR, 13C NMR and UV spectral studies. The density functional theory (DFT) calculations have been executed for the 5MBOT using B3LYP/6-31++G (d, p) basis set. The fundamental modes of the vibrations were designated by the potential energy distribution (PED), and the computed and experimental values support each other. The 1H NMR and 13C NMR chemical shifts of 5MBOT were estimated by gauge-including atomic orbitals (GIAO) method and compared with the experimental chemical shifts. The UV-Vis method used to study the visible absorption maxima (λmax) by using Time-Dependent DFT. Further, the Mulliken population analysis (MPA), natural population analysis (NPA) charges, thermodynamic properties at different temperatures were presented. The calculated HOMO and LUMO energies show that charge transfer within the molecule. The natural bonds orbital (NBO) also computed. Optoelectronic properties have been carried out by combination of DFT calculations and molecular dynamics (MD) simulations, in order to assess the potential of this structure for applications in organic electronics. Further, the study encompassed calculations of reorganization energies for holes and electrons and charge transfer rates. DFT calculations have been also used in order to identify locations possibly sensitive towards the autoxidation mechanism, which correlates between bond dissociation energy for hydrogen abstraction and the mechanism. The MD simulations have been used to understand interaction of 5MBOT with water molecules. Molecular docking studies reveals the antifungal activity of 5MBOT may be due to hydrogen bonding and hydrophobic interactions with different antifungal proteins.

Growth, spectral, anisotropic, second and third order nonlinear optical studies on potential nonlinear optical crystal anilinium perchlorate (AP) for NLO device fabrications.

A new semiorganic nonlinear optical material anilinium perchlorate was grown by the slow evaporation technique using water as solvent. The solubility and meta stable zone width were determined. The anilinium perchlorate crystal belongs to orthorhombic system with noncentrosymmetric space group P212121. The presence of various functional groups was identified by FT-IR FT-Raman spectrum. The morphology of the anilinium perchlorate crystal was studied. From this morphology, anilinium perchlorate crystal plate was cut along three prominent planes, such as (001), (010) and (20-1). The thermal stability of the crystal was determined using TG-DTA studies. The hardness, laser damage threshold, transmittance, reflectance, experimental refractive index of the crystal was found. The particle size dependent second harmonic generation efficiency for anilinium perchlorate was evaluated by Kurtz-Perry powder method using Nd:YAG laser, which established the existence of phase matching. The third order nonlinear refractive index and nonlinear absorption coefficient of the grown crystal were measured by Z-scan studies.

Vibrational analysis using FT-IR, FT-Raman spectra and HF-DFT methods and NBO, NLO, NMR, HOMO-LUMO, UV and electronic transitions studies on 2,2,4-trimethyl pentane.

In this work, the vibrational spectral analysis was carried out by using Raman and infrared spectroscopy in the range 100-4000cm(-1)and 50-4000cm(-1), respectively, for 2,2,4-Trimethyl Pentane, TMP (C8H18) molecule. The molecular structure, fundamental vibrational frequencies and intensity of the vibrational bands are interpreted with the aid of structure optimizations and geometrical parameter calculations based on Hartree Fock (HF) and density functional theory (DFT) method with 6-311++G(d,p) basis set. The scaled B3LYP/6-311++G(d,p) results shows the best agreement with the experimental values over the other method. The calculated HOMO and LUMO energies shows that charge transfer within the molecule. The physical reactions of single bond hydrocarbon TMP were investigated. The results of the calculations were applied to simulate spectra of the title compound, which shows the excellent agreement with observed spectra. Besides, Mulliken atomic charges, UV, frontier molecular orbital (FMO), MEP, NLO activity, Natural Bond-Orbital (NBO) analysis, NMR and thermodynamic properties of title molecule were also performed.

NBO, HOMO-LUMO, UV, NLO, NMR and vibrational analysis of veratrole using FT-IR, FT-Raman, FT-NMR spectra and HF-DFT computational methods.

This work deals with FT-IR, FT-Raman and FT-NMR spectral analysis and NBO, NLO, HOMO-LUMO and electronic transitions studies on veratrole. The molecular structure, fundamental vibrational frequencies and intensity of the vibrational bands were interpreted with the aid of structure optimizations and geometrical parameter calculations based on Hartree-Fock (HF) and density functional theory (DFT) method with 6-311++G(d, p) basis set. A study on the electronic properties, such as HOMO and LUMO energies were performed by time independent DFT approach. In addition, molecular electrostatic potential (MEP), Natural Bond-Orbital (NBO) analysis and thermodynamic properties were performed. The (1)H and (13)C nuclear magnetic resonance (NMR) chemical shifts of the molecule were calculated by gauge independent atomic orbital (GIAO) method and compared with experimental chemical shift.

Vibrational frequency analysis, FT-IR, FT-Raman, ab initio, HF and DFT studies, NBO, HOMO-LUMO and electronic structure calculations on pycolinaldehyde oxime.

In this work, the vibrational spectral analysis is carried out by using Raman and infrared spectroscopy in the range 100-4000 cm(-1)and 50-4000 cm(-1), respectively, for pycolinaldehyde oxime (PAO) (C6H6N2O) molecule. The vibrational frequencies have been calculated and scaled values are compared with experimental FT-IR and FT-Raman spectra. The structure optimizations and normal coordinate force field calculations are based on HF and B3LYP methods with 6-311++G(d,p) basis set. The results of the calculation shows excellent agreement between experimental and calculated frequencies in B3LYP/6-311++G(d,p) basis set. The optimized geometric parameters are compared with experimental values of PAO. The non linear optical properties, NBO analysis, thermodynamics properties and mulliken charges of the title molecule are also calculated and interpreted. A study on the electronic properties, such as HOMO and LUMO energies, are performed by time-dependent DFT (TD-DFT) approach. Besides, frontier molecular orbitals (FMO), molecular electrostatic potential (MEP) are performed. The effects due to the substitutions of CH=NOH ring are investigated. The (1)H and (13)C nuclear magnetic resonance (NMR) chemical shifts of the molecule are calculated by the gauge independent atomic orbital (GIAO) method and compared with experimental results.

Growth, spectroscopy properties and DFT based PCM calculations of guanidinium chlorochromate.

Nonlinear optical single crystals of guanidinium chlorochromate [GCC] are grown by slow evaporation solution growth technique using water as the solvent. Purity of crystals is increased by the method of recrystallization. The solubility of the material is measured at various temperatures in de-ionized water. The grown crystals are characterized by single crystal XRD for obtaining unit cell parameters. The presence of functional groups and modes of vibrations are identified by FT-IR spectroscopy. The chemical structure of crystal is established by FT-NMR techniques. The UV-vis-NIR spectrum of GCC shows less absorption and good transmittance in the entire visible region enabling its use in optical application. Also, the Kurtz powder second harmonic generation test shows that the compound is a potential material for optical second harmonic generation. The theoretical vibration frequency of HC(NH2)3 and [C(NH2)3]2 are analyzed in different solvent media.

FT-IR, FT-Raman, ab initio, HF and DFT studies, NBO, HOMO-LUMO and electronic structure calculations on 4-chloro-3-nitrotoluene.

In this work, the vibrational spectral analysis was carried out by using Raman and infrared spectroscopy in the range 100-4000 cm(-1) and 50-4000 cm(-1), respectively, for 4-chloro-3-nitrotoluene (C7H6NO2Cl) molecule. The molecular structure, fundamental vibrational frequencies and intensity of the vibrational bands are interpreted with the aid of structure optimizations and normal coordinate force field calculations based on Hartree Fock (HF) and density functional theory (DFT) method and different basis sets combination. The complete vibrational assignments of wavenumbers were made on the basis of potential energy distribution (PED). The scaled B3LYP/6-311++G(d,p) results show the best agreement with the experimental values over the other methods. The calculated HOMO and LUMO energies shows that charge transfer within the molecule. The effects due to the substitutions of methyl group, nitro group and halogen were investigated. The results of the calculations were applied to simulate spectra of the title compound, which show excellent agreement with observed spectra. Besides, frontier molecular orbitals (FMO), molecular electrostatic potential (MEP) and thermodynamic properties were performed.

Synthesis, growth, structural, spectroscopic and optical studies of a semiorganic NLO crystal: zinc guanidinium phosphate.

The semi-organic nonlinear optical (NLO) crystal, zinc guanidinium phosphate (ZGuP) has been grown through synthesis between zinc sulphate, guanidine carbonate and orthophosphoric acid from its aqueous solution by slow solvent evaporation technique. Solubility of the synthesized material has been determined for various temperatures using water as solvent. The grown crystal has been characterized by powder X-ray diffraction to confirm the crystal structure. Investigation has been carried out to assign the vibrational frequencies of the grown crystals by Fourier transform infrared spectroscopy technique. (1)H and (13)C FT-NMR have been recorded to elucidate the molecular structure. The optical absorption study confirms the suitability of the crystal for device applications. The second harmonic generation (SHG) efficiency of ZGuP is found to be 1.825 times that of potassium dihydrogen phosphate (KDP). Thermal behavior of the grown crystals has been studied by thermogravimetric and differential thermal analysis. The mechanical properties of the grown crystals have been studied using Vickers microhardness tester.

Spectral investigations of preferential solvation and solute-solvent interactions of 1,4-dimethylamino anthraquinone in CH2Cl2/C2H5OH mixtures.

The optical absorption and IR spectra of 1,4-dimethylamino anthraquinone (1,4-DMAAQ) in CH(2)Cl(2)/C(2)H(5)OH mixtures have been investigated. The preferential solvation of 1,4-DMAAQ in CH(2)Cl(2)/C(2)H(5)OH mixed solvents has been studied by monitoring the charge transfer band of 1,4-DMAAQ. The optical absorption spectral study indicates that 1,4-DMAAQ is preferentially solvated by CH(2)Cl(2) in CH(2)Cl(2)/C(2)H(5)OH mixtures. This can be confirmed by the observed index of preferential solvation value (delta(s1)) as well as higher mole fraction of CH(2)Cl(2) in the solvation microsphere (x(1)(L)) than in the bulk solvent (x(1)). The CH(2)Cl(2) molecules become more available to enter the solvation shell of 1,4-DMAAQ because of the hydrogen bonded clusters formed by ethanol molecules. This is also evident from the non-linear behavior of the transition energy (E(12)) as well as the absence of synergistic behavior. IR spectral studies show that the observed shifts in the nu(CO) and nu(NH) of 1,4-DMAAQ are due to the dipole-dipole interaction between the 1,4-DMAAQ and the associated ethanol.