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1.
J Mol Model ; 26(12): 341, 2020 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-33200284

RESUMO

HER-2 type breast cancer is one of the most aggressive malignancies found in women. Tucatinib is recently developed and approved as a potential medicine to fight this disease. In this manuscript, we present the gross structural features of this compound and its reactivity and wave function properties using computational simulations. Density functional theory was used to optimise the ground state geometry of the molecule and molecular docking was used to predict biological activity. As the electrons interact with electromagnetic radiations, electronic excitations between different energy levels are analysed in detail using time-dependent density functional theory. Various intermolecular and intermolecular interactions are analysed and reaction sites for attacking electrophiles and nucleophiles identified. Information entropy calculations show that the compound is inherently stable. Docking with COVID-19 proteins show docking score of - 9.42, - 8.93, - 8.45 and - 8.32 kcal/mol respectively indicating high interaction between the drug and proteins. Hence, this is an ideal candidate to study repurposing of existing drugs to combat the pandemic.


Assuntos
Antineoplásicos/química , Antivirais/química , Betacoronavirus/química , Elétrons , Oxazóis/química , Inibidores de Proteases/química , Piridinas/química , Quinazolinas/química , Proteínas não Estruturais Virais/antagonistas & inibidores , Antineoplásicos/metabolismo , Antivirais/metabolismo , Betacoronavirus/enzimologia , Sítios de Ligação , Cisteína Endopeptidases/química , Cisteína Endopeptidases/metabolismo , Reposicionamento de Medicamentos , Humanos , Ligação de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Oxazóis/metabolismo , Inibidores de Proteases/metabolismo , Ligação Proteica , Domínios e Motivos de Interação entre Proteínas , Estrutura Secundária de Proteína , Piridinas/metabolismo , Teoria Quântica , Quinazolinas/metabolismo , Termodinâmica , Proteínas não Estruturais Virais/química , Proteínas não Estruturais Virais/metabolismo
2.
J Mol Liq ; 318: 114082, 2020 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-32863490

RESUMO

Melatonin is a natural hormone from the pineal gland that regulates the sleep-wake cycle. We examined the structure and physico-chemical properties of melatonin using electronic structure methods and molecular-mechanics tools. Density functional theory (DFT) was used to optimise the ground-state geometry of the molecule from frontier molecular orbitals, which were analysed using the B3LYP functional. As its electrons interacted with electromagnetic radiation, electronic excitations between different energy levels were analysed in detail using time-dependent DFT with CAM-B3LYP orbitals. The results provide a wealth of information about melatonin's electronic properties, which will enable the prediction of its bioactivity. Molecular docking studies predict the biological activity of the molecules against the coronavirus2 protein. Excellent docking scores of -7.28, -7.20, and -7.06 kcal/mol indicate that melatonin can help to defend against the viral load in vulnerable populations. Hence it can be investigated as a candidate drug for the management of COVID.

3.
J Mol Model ; 26(9): 256, 2020 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-32885337

RESUMO

Cocrystals are of immense applications in crystal engineering and pharmaceutical chemistry. Hydrochlorothiazide is found to form cocrystals with picolinamide (H1), tetramethylpyrazine (H2) and piperazine (H3). It was characterized using IR spectra, and quantum mechanical calculations for geometry and other properties. Frontier orbital energies are used to predict the energy properties and model the possible charge transfer between the constituents of the cocrystal. The frontier molecular orbital analysis indicates chemical reactivity and bioactivity of the cocrystals. The MEP surface reveals the various reactive surfaces in the cocrystal system, which is very important in deciding various biological activities. The UV-Vis spectra show the possible electronic transitions of the molecules. Simulated electronic spectra using TDDFT method with CAM-B3LYP functional were used to investigate the suitability of the cocrystals to be used in DSSC. Moreover, the molecular docking analysis proves that the cocrystals can act as potential inhibitors and paves the way for developing effective drugs.

4.
J Mol Model ; 26(9): 254, 2020 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-32876867

RESUMO

Spectroscopic analysis and different quantum mechanical studies of four pharmaceutically active compounds phenacetin, p-acetanisidide, 4'-butoxyacetanilide, and 4'-(3-chloropropoxy)acetanilide are reported in this manuscript. Simulated IR spectrum of these compounds was compared with experimentally available data, and essential functional group assignments were made. We also report the frontier orbital properties and other derived local energy descriptors which talks about the relative stability and reactivity. Photovoltaic efficiency of the compounds was studied from the simulated electronic spectra. The compound was found to interact with graphene and fullerene, to form molecular self-assembly. These self-assemblies showed tremendous enhancement in various physicochemical properties when compared with its constituents. The nature of the interactions between studied chemical species was discussed with the help of chemical reactivity principles. Biological activity of the compounds was predicted using molecular docking studies. It is interesting to see that on adsorption with a graphene/fullerene surface, all adsorbed complex shows enhancement in the Raman activity giving surface enhanced Raman spectra (SERS). This can be used for the detection of these drugs in a pharmacological or biological sample. Interestingly the graphene/fullerene drug molecular assembly shows enhanced biological activity when compared with individual drug molecules. Graphical abstract.

5.
J Biomol Struct Dyn ; : 1-7, 2020 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-32657232

RESUMO

Letrozole and metronidazole are two commonly used drugs for the management of breast cancer and parasitic infections, respectively. This manuscript attempts to study their structure, geometry, search for stable conformers using relaxed potential energy scan, spectral properties, quantum mechanical properties like energy and reactivity descriptors, intra molecular electron transfer properties, non-linear properties etc using various computational tools. It is found that these compounds will form a self-assembly with graphene sheets and fullerenes and exhibit a surface-enhanced Raman spectra and enhancement in non-linear optical properties when compared to the single molecule. The electronic absorption behavior of the compounds was studied using TD-DFT method. Global chemical reactivity descriptors and activity sites toward electrophilic and nucleophilic attack have been discussed. Studies of intra molecular electron transfer gave information about the relative stability of the compounds. Molecular docking studies indicate that the pure compounds and their self-assemblies with graphene have excellent biological activities. Communicated by Ramaswamy H. Sarma.

6.
Heliyon ; 6(6): e04106, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32529077

RESUMO

Pyrroles are an exciting class of organic compounds with immense medicinal activities. This manuscript presents the structural and quantum mechanical studies of 1-(2-aminophenyl) pyrrole using X-Ray diffraction and various spectroscopic methods like Infra-Red, Raman, Ultra-violet and Fluorescence spectroscopy and its comparison with theoretical simulations. The single-crystal X-ray diffraction values and optimized geometry parameters also were within the agreeable range. A fully relaxed potential energy scan revealed the stability of the possible conformers of this molecule. We present the density functional theory results and assignment of the vibrational modes in the infrared spectrum. The experimental and scaled simulated vibrations matched when density functional theory simulations (B3LYP functional with 6-311++G∗∗). The electronic spectrum was simulated using time-dependent density functional theory with CAM-B3LYP functional in dimethylsulphoxide solvent. The fluorescence spectrum of the compound was studied at different excitation wavelengths in the dimethylsulphoxide solvent. The stability of the molecule by intramolecular electron transfer by hyperconjugation was studied with the natural bond orbital analysis. Frontier molecular orbitals and molecular electrostatic potentials of the compound gave an idea about the reactive behaviour of the compounds. Prediction of activity spectral studies followed by docking analysis indicated that the molecule is active against arylacetonitrilase inhibitor.

7.
Spectrochim Acta A Mol Biomol Spectrosc ; 236: 118329, 2020 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-32299039

RESUMO

In this work, we report the synthesis of two receptors for fluoride ions based on acyl hydrazone, such as N'-[(1Z)-1-(4-fluorophenyl)ethylidene]benzohydrazide (R1) and N'-[(1Z)-1-(2-hydroxyphenyl)ethylidene]benzohydrazide (R2). The receptors R1 and R2 were synthesized from the corresponding ketones and benzoic acid hydrazide and characterized spectroscopically by UV-visible, IR and 1HNMR techniques. The response of R1 and R2 towards different anions was studied colourimetrically in acetonitrile. The receptors exhibited a specific response towards fluoride ions. Further studies of 1:1 composition of receptors, R1/R2:fluoride ions by different spectroscopic techniques such as UV-Visible, IR and 1HNMR spectroscopy indicated the participation of -NH proton of the receptors in the sensing action through the hydrogen bonding. To understand the mechanism, Time-Dependent Density Functional Theory (TD-DFT) studies were done using the CAM-B3LYP/6311G++ (3df,2p) with Grimme's D3BJ empirical dispersion basis set. The studies supported the role of hydrogen bonding interaction of -NH and-OH protons of the receptors with the fluoride ions.

8.
Spectrochim Acta A Mol Biomol Spectrosc ; 224: 117414, 2020 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-31376725

RESUMO

This article represents the spectroscopic and computational studies of two new pyrazine compounds. In order to establish the structure and functional nature of the compounds, we have employed Fourier transformed infrared (FT-IR) and Raman spectra, nuclear magnetic resonance (NMR) spectra, and ultraviolet (UV) absorptions and have compared them with the simulated computational spectra and found that they are in the agreeable range. Simulated hyperpolarisability values are used to obtain the nonlinear optic (NLO) activity of the compound, to be used in organic electronic materials. The charge transfer and related properties was investigated by the simulation of electronic spectrum with time dependent density functional theory (TD-DFT). Natural transition orbitals (NTO) provides information about which region of the molecules are more involved in the electronic transitions and the charge transfer properties for the lowest energy excitation have been analyzed on the basis of electron density variation. Molecular dynamics simulations provide information about the behavior of the molecule in solutions. Frontier orbital analysis and study of various reactivity descriptors like ALIE and Fukui provided deep knowledge on the reactivity side. Molecular docking has been also performed to investigate the interaction between title molecules and exhibits inhibitory activity against Pseudomonas aeruginosa Enoyl-Acyl carrier protein reductase (Fabl).


Assuntos
Pirazinas , Antibacterianos/análise , Antibacterianos/química , Antibacterianos/metabolismo , Proteínas de Bactérias/química , Proteínas de Bactérias/metabolismo , Descoberta de Drogas , Simulação de Acoplamento Molecular , Pirazinas/análise , Pirazinas/química , Pirazinas/metabolismo , Análise Espectral , Eletricidade Estática
9.
Spectrochim Acta A Mol Biomol Spectrosc ; 228: 117580, 2020 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-31748158

RESUMO

A set of experimental and computational techniques have been applied for the understanding of fundamental spectroscopic and reactive properties of 3-(3,4-dichlorophenyl)-1,1-dimethylurea (diuron) compound. Experimental techniques employed in this study encompassed spectroscopic characterization via IR and Raman approaches, while optical properties were studied by measurements of UV/Vis spectra. The thermogravimetric analysis was also studied in order to analyze the stability of diuron. Aside from the determination of reactive properties, DFT calculations on isolated molecules were also used to thoroughly visualize and analyze spectroscopic properties such as IR and UV/Vis. MD simulations were used in order to understand interactions with water, while periodic DFT calculations were used in order to analyze band structure and density of states of the diuron crystal structure. Since the crystal structure of diuron is known, it was used in order to extract the relevant molecular pairs and investigate interactions between them by DFT and symmetry adapted perturbation theory approaches (SAPT).

10.
Heliyon ; 5(11): e02825, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31763480

RESUMO

The structural, spectroscopic various physico-chemical and biological characteristics of the organic molecule benzil (BZL) and derivatives, 1,2-bis(4-methylphneyl)-1,2-ethanedione (DMB), 4,4'-difluorobenzil (DFB), 4,4'-dichlorobenzil (DCB) and 4,4'-dibromobenzil (DBB) have been studied by various computational methods. The experimental and scaled simulated Raman and IR spectra were compared and found close agreement. Assignments of important peaks are also presented. Detailed information pertaining to the local and global reactivity and other properties like electrophilic and nucleophilic characteristics were analysed. The hyperactive pressure was measured in terms of polarizability and corresponding biological properties were validated to identity reactive sites. Prediction of Activity Spectral Studies (PASS) predicts the biological activity of the compounds and it is found that the candidate molecules can be used as feruloyl esterase inhibitor, bisphosphoglycerate phosphatase inhibitor and Prolylaminopeptidase inhibitor. The crystals structures of those receptors are taken from the protein data bank and docking studies indicates stable complex with the receptors and candidate molecules. Light harvesting efficiency, followed by photovoltaic modelling shows that DMB is the best compound to be used in the DSSC to get the best output.

11.
Heliyon ; 5(7): e02175, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31388594

RESUMO

The organic molecule tenoxicam and similar derivatives, piroxicam and isoxicam have been studied by quantum chemical theory (DFT), FT-Raman and FT-IR. By FMOs energies the charge transfer inside the molecules are obtained. The UV-Vis spectra of the compounds are simulated to study the electronic transition in the target molecules. By using natural bond orbital (NBO), charge delocalization analyzes arising from hyper conjugative interactions and the stability of the molecules are obtained. First order hyperpolarizability of piroxicam is higher than that of isoxicam and tenoxicam. The reactive areas are thoroughly studied by MEP. Prediction of Activity Spectra gives activities, anti-inflammatory, CYP2C9 substrate and gout treatment. Docked ligands form a stable complex with the receptors.

12.
J Fluoresc ; 29(4): 1013-1027, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31309390

RESUMO

A fluoro-based Schiff base (E)-2-fluoro-N'-(1-(4-nitrophenyl)ethylidene)benzohydrazide (FNEB) has been synthesized from condensation of 2-fluorobenzohydrazide and 4'-nitroacetophenone catalyzed by glacial acetic acid with ethanol as the solvent. The dipole moment of FNEB in both the electronic states were found using different solvatochromic approaches such as Lippert-Mataga, Bakhshiev, Kawski-Chamma-Viallet, Reichardt and Bilot-Kawski. The experimental ground state dipole moment of FNEB was calculated using Guggenheim-Debye method and theoretical ground state dipole moment using Bilot-Kawski solvatochromic approach. The solvatochromic behavior of the Schiff base in different solvents was studied using absorption and emission spectra. Catalan and Kamlet-Abboud-Taft parameters were used from the multiple linear regression (MLR) analysis in order to study the solute-solvent interaction. The dipole moments were also calculated using Time Dependent-Density Functional Theory (TD-DFT). The chemical stability of FNEB was determined using computational and Cyclic Voltammetry by the use of obtained energy gap between the frontier orbitals. Using the frontier orbitals energy gap, global reactivity parameters were computed. Further, Light Harvesting efficiency was determined to comprehend the photovoltaic property of the Schiff base.

13.
Heliyon ; 5(6): e01987, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31304416

RESUMO

1,1-Dimethyl-3-phenylurea (known as fenuron) which is a phenyl urea-based widely used herbicide exhibits interesting structural and conformational properties and a notable biological activity. A detailed analysis on the vibrational, molecular and electronic characteristics of fenuron has been carried out. Potential energy scans (PESs) performed at the B3LYP/6-311++G(d,p) level of theory predicted two possible minima corresponding to the optimized anti and synforms resulting from the internal rotation about the N-C bond. The presence of an auxochrome together with the interaction with DMSO solvent exhibited a blue shift corresponding to the C=O orbitals. Delocalization of HOMO and LUMO orbital facilitated the charge transfer effect in the molecule. The calculated HOMO-LUMO energies, chemical potential, energy gap and global hardness suggested a low softness value for the compound while its biological activity was described by the value of electrophilicity. Chlorine substitution in the phenyl ring influenced the orbital delocalization for ortho and para substitutions but that of meta remained unaffected. NLO properties were noticed to increase due to chlorine substitution in the parent molecule. The docking results suggested that the compound exhibits an inhibitory activity against mitochondrial ubiquinol-cytochrome-c reductase and can be developed as a potential anticancer agent.

14.
J Mol Graph Model ; 88: 237-246, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30772654

RESUMO

Quantum chemical calculations at the ωB97XD/6-311++G(d,p) level of theory have been executed to investigate the effect of substituents via hydrogen-bonded and triel-bonded complexes between uracil (U), thymine (T) and 5-fluorouracil (5FU) with HCl for the former complexes, and with BH3 and AlH3 for the latter complexes. These calculations are supported by single-point energy calculations at MP2/6-311++G(d,p) and CCSD/6-31 + G(d,p) levels of theory, Natural Bond Orbital (NBO) and Molecular Electrostatic Potentials (MEPs) analyses, and global/local reactivity descriptors. The results reveal that triel-bonded complexes are strongly bounded than hydrogen-bonded ones, and Al-containing dimers stronger than B-containing ones. In addition, as the central triel atom grows in size, B-containing dimers (B-O triel bond) are accompanied by weak B-H⋯O unconventional H-bonds. According to local reactivity descriptors, the B-O triel bond is hard-hard interaction that indicates that the association is primarily charge controlled, while the Al-O triel bond is soft-soft interaction that is primarily orbital controlled. In both Hydrogen as well as triel-bonded complexes, the α-methylation slightly overestimates the binding strength of U, while the α-fluorination exerts the opposite role by underestimating the binding strength of U. In overall, the effect of substituents on the bond strength and thus on the regioselectivity is very small, suggesting a competition between the two carbonyl groups in terms of structures and binding energies.


Assuntos
Elétrons , Fluoruracila/química , Halogenação , Ácido Clorídrico/química , Metilação , Ligação de Hidrogênio , Modelos Químicos , Modelos Moleculares , Estrutura Molecular , Análise Espectral
15.
Comput Biol Chem ; 78: 153-164, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30530296

RESUMO

A derivative of naphthaquinone, 2-((1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)amino)naphthalene-1,4-dione (DPDHN) was synthesized from lawsone by ultrasound accelerated technique. The compound was characterized by elemental analysis, IR, UV-vis, NMR and mass spectral studies. Single crystal X-ray diffraction studies revealed that the compound crystallized in monoclinic space group P21/c. Density functional calculations of DPDHN was performed using DFT (B3LYP) method with 6-311G (5D, 7F) basis set, geometrical optimization best fit to single crystal XRD values. The charge delocalization has been analyzed using natural orbital (NBO) analysis. Effects of halogenations at ortho, meta and para positions in the title compound is discussed for frontier molecular orbital analysis, molecular electrostatic potential plots and nonlinear optical properties. It exhibited significant antioxidant property. To predict the anticancer activity of the compound, molecular docking studies were done using Schrödinger software. Molecular docking studies for DPDHN was performed on the active site of protein kinase CK2 (PDB ID: 2OXX, 1M2R and 1M2P) and to explore the estrogen receptor binding ability, the target protein with PDB ID: 3ERT and 2YLY were selected. Docking scores of the designed compound was compared with FDA approved drugs, Tamoxifen, Daunorubicin and Doxorubicin. The compound DPDHN exhibited good Glide scores for all the proteins. Glide score of DPDHN (PDB ID: 2YLY) was -9.67 kcal/mol which was as good as the currently used breast cancer drug, Tamoxifen (-10.37 kcal/mol) and found better than the drug Doxorubicin (-7.3 kcal/mol). Lead compound that satisfies predefined minimum criteria further structure and activity optimization. In the present work, hence it was further subjected to in vitro studies towards human breast cancer (MCF-7) and colon cancer (HCT-15) cell lines. The IC50 value of compound DPDHN in MCF-7 cells was 15.21 µM and that of HCT-15 was 39.21 µM which was a lower value and better than that of lawsone. Therefore DPDHN exhibited much higher toxicity towards MCF-7 cell lines. Thus, the results indicate that DPDHN is a potential anti cancer lead molecule especially for breast cancer studies.


Assuntos
Antineoplásicos/farmacologia , Teoria da Densidade Funcional , Antineoplásicos/síntese química , Antineoplásicos/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Cristalografia por Raios X , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Células MCF-7 , Modelos Moleculares , Estrutura Molecular , Relação Estrutura-Atividade
16.
Spectrochim Acta A Mol Biomol Spectrosc ; 204: 328-339, 2018 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-29957411

RESUMO

A new chloranilate compound with 1-(2-fluorophenyl)piperazine has been synthesized and characterized using spectroscopic methods and X-ray diffraction. The atomic arrangement can be described by an H-bonded 3D network, formed by anionic entities, organic cations and H2O molecules linked together via NH…O, OH…Cl, CH…Cl and CH…O hydrogen bonds. The vibrational absorption bands of the various characteristic groups of this compound have been identified by infrared spectroscopy. Moreover, the thermal and dielectric analyses have shown that the title compound has a phase transition at 393 K. The surface mapped over the dnorm property, highlights the A⋯H (AO, C, Cl and F) as the main intermolecular contacts. On the other hand, the geometry, intermolecular bonds and harmonic vibrational frequencies of the title molecule have been investigated using the B3LYP/6-31G (d, p) method. The stability of the structure obtained, as well as the charge transfer within the molecule, have been confirmed by determining the energies of the HOMO and LUMO levels and the theoretical gap energy. Molecular docking studies of the title compound have also been conducted as part of this study.

17.
Biopolymers ; 91(5): 351-60, 2009 May.
Artigo em Inglês | MEDLINE | ID: mdl-19137576

RESUMO

xDNA is a modified DNA, which contains natural as well as expanded bases. Expanded bases are generated by the addition of a benzene spacer to the natural bases. A set of AMBER force-field parameters were derived for the expanded bases and the structural dynamics of the xDNA decamer (xT5' G xT A xC xG C xA xG T3').(xA5' C T xG C G xT A xC A3') was explored using a 22 ns molecular dynamics simulation in explicit solvent. During the simulation, the duplex retained its Watson-Crick base-pairing and double helical structure, with deviations from the starting B-form geometry towards A-form; the deviations are mainly in the backbone torsion angles and in the helical parameters. The sugar pucker of the residues were distributed among a variety of modes; C2' endo, C1' exo, O4' endo, C4' exo, C2' exo, and C3' endo. The enhanced stacking interactions on account of the modification in the bases could help to retain the duplex nature of the helix with minor deviations from the ideal geometry. In our simulation, the xDNA showed a reduced minor groove width and an enlarged major groove width in comparison with the NMR structure. Both the grooves are larger than that of standard B-DNA, but major groove width is larger than that of A-DNA with almost equal minor groove width. The enlarged groove widths and the possibility of additional hydration in the grooves makes xDNA a potential molecule for various applications.


Assuntos
DNA/química , Simulação de Dinâmica Molecular , Sequência de Bases , Carboidratos/química , DNA/genética , DNA/metabolismo , Ligação de Hidrogênio , Dados de Sequência Molecular , Conformação de Ácido Nucleico , Água
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