Spectroscopic, quantum chemical investigation and molecular docking studies on N-(2-benzoylamino) phenyl benzamide: A novel SARS-CoV-2 drug.

The present work describes the structural and spectral properties of N-(2-benzoylamino) phenyl benzamide (NBPB). The geometrical parameters of NBPB molecule such as bond lengths, bond angles and dihedral angles are calculated and compared with experimental values. The assigned vibrational wave numbers are in good agreement with the experimental FTIR and FT Raman spectra. The vibrational frequency of C=O stretching was downshifted to a lower wave number (red shift) due to mesomeric effect. The UV-Vis spectrum of the title compound was simulated and validated experimentally. The energy gap and charge transfer interaction of the title molecule were studied using frontier molecular orbital analysis. The electrophilic and nucleophilic reactivity sites of NBPB were investigated through the analysis of the molecular electrostatic potential surface and the Fukui function. An assessment of the intramolecular stabilization interactions of the molecule was performed using natural bond orbital analysis. The drug-likeness parameter was calculated. To investigate the inhibitory potential of the molecule, molecular docking analysis was conducted against SARS-CoV-2 proteins, revealing its capability to serve as a novel inhibitor against SARS-CoV-2. The high binding affinity of NBPB molecule was due to the presence of hydrogen bonds along with different hydrophobic interactions between the drug and the SARS-CoV-2 protein receptor. Hence, the title molecule is identified to be a potential candidate for SARS-CoV-2.

Spectroscopic investigations, quantum chemical, drug likeness and molecular docking studies of methyl 1-methyl-4-nitro-pyrrole-2-carboxylate: A novel ovarian cancer drug.

Density functional theory (DFT) calculation was used to analyse the structural and vibrational properties of Methyl 1-Methyl-4-nitro-pyrrole-2-carboxylate (MMNPC) using the cc-pVTZ basis set. The potential energy surface scan and the most stable molecular structure were optimized using Gaussian 09 program. A potential energy distribution calculation was used to calculate and assign vibrational frequencies using the VEDA 4.0 program package. The Frontier Molecular Orbitals (FMOs) were analysed to determine their related molecular properties. Ab initio density functional theory (B3LYP/cc-pVTZ) method with basis set was used to calculate 13C NMR chemical shift values of MMNPC in the ground state. Fukui function and molecular electrostatic potential (MEP) analysis confirmed the bioactivity of the MMNPC molecule. The charge delocalization and stability of the title compound were studied using natural bond orbital analysis. All experimental spectral values from FT-IR, FT-Raman, UV-VIS, and 13C NMR are in good agreement with the value calculated by the DFT. Molecular docking analysis was carried out to find the MMNPC compound that can be used as a potential drug development candidate for ovarian cancer.

Density Functional Theory, Molecular Dynamics and AlteQ Studies Approaches of Baimantuoluoamide A and Baimantuoluoamide B to Identify Potential Inhibitors of Mpro Proteins: a Novel Target for the Treatment of SARS COVID-19.

COVID-19 has resulted in epidemi conditions over the world. Despite efforts by scientists from all over the world to develop an effective va ine against this virus, there is presently no recognized cure for COVID-19. The most succeed treatments for various ailments come from natural components found in medicinal plants, which are also rucial for the development of new medications. This study intends to understand the role of the baimantuoluoamide A and baimantuoluoamide B molecules in the treatment of Covid19. Initially, density functional theory (DFT) used to explore their electronic potentials along with the Becke3-Lee-Yang-Parr (B3LYP) 6-311 + G(d, p) basis set. A number of characteristics, including the energy gap, hardness, local softness, electronegativity, and electrophilicity, have also been calculated to discuss the reactivity of mole ules. Using natural bond orbital, the title compound's bioactive nature and stability were investigated. Further, both compounds potential inhibitors with main protease (Mpro) proteins, molecular dynamics simulations and AlteQ investigations also studied. Supplementary Information: The online version contains supplementary material available at 10.1134/S0021364023600039.

Synthesis, spectroscopic (FT-IR, FT-Raman, NMR & UV-Vis), reactive (ELF, LOL, Fukui), drug likeness and molecular docking insights on novel 4-[3-(3-methoxy-phenyl)-3-oxo-propenyl]-benzonitrile by experimental and computational methods.

The spectroscopic analysis such as FT-IR, FT-Raman, UV-Vis and NMR are conducted for the synthesized molecule by both experimental and theoretical approach. The theoretical computations were achieved by DFT method with B3LYP functional and 6-311 ++ G (d, P) basis set. Firstly the geometrical parameters obtained by DFT are compared with the related experimental parameters. Experimental FT-IR and FT-Raman spectra of the title molecule have been acquired. The vibrational analysis is conducted and the assignments concerned to the observed bands are mentioned through the potential energy distribution (PED). The GIAO method was employed for theoretical NMR analysis and the results are compared with experimental chemical shifts. In accumulation to these analyses NLO, NBO, FMO and MEP analysis have been conducted to understand the nature of the molecule. ELF and LOL were performed. The drug likeness and molecular docking studies also conducted. The potency of inhibition of molecule against MPRO and PLPRO receptors has been performed using molecular docking studies.

Spectroscopic characterization, DFT studies, molecular docking and cytotoxic evaluation of 4-nitro-indole-3-carboxaldehyde: A potent lung cancer agent.

The 4-nitro-1H-indole-carboxaldehyde (NICA) molecule was characterized experimentally using FT-IR, FT-Raman and UV-Vis spectra, and it was studied theoretically using DFT calculations. The optimized structure of the NICA molecule was determined by DFT calculations using B3LYP functional with cc-pVTZ basis set. The electron localization function (ELF) and local orbital localizer (LOL) studies were performed to visualize the electron delocalization in the molecule. The experimental and theoretical wavenumbers of the title molecule were assigned using VEDA 4.0 program. The charge delocalization and stability of the title molecule were investigated using natural bond orbital (NBO) analysis. Frontier molecular orbitals (FMOs) and related molecular properties were calculated. UV-Vis spectrum was calculated theoretically and validated experimentally. The reactive sites of the molecule were studied from the MEP surface and Fukui function analysis. The molecular docking analysis reveals that the NICA ligand shows better inhibitory activity against RAS, which causes lung cancer. The in vitro cytotoxic activity of the molecule against human lung cancer cell lines (A549) was determined by MTT assay. Thus, the NICA molecule can be used as a potential candidate for the development of the drug against lung cancer.

Inducing remission of Type 2 diabetes in the Caribbean: findings from a mixed methods feasibility study of a low-calorie liquid diet-based intervention in Barbados.

AIM: In a high proportion of people with recently diagnosed Type 2 diabetes, a short (2-3-month) low-calorie diet is able to restore normal glucose and insulin metabolism. The aim of this study was to determine the feasibility of this approach in Barbados. METHODS: Twenty-five individuals with Type 2 diabetes diagnosed within past 6 years, not on insulin, BMI ≥ 27 kg/m2 were recruited. Hypoglycaemic medication was stopped on commencement of the 8-week liquid (760 calorie) diet. Insulin response was assessed in meal tests at baseline, 8 weeks and 8 months. Semi-structured interviews, analysed thematically, explored participants' experiences. 'Responders' were those with fasting plasma glucose (FPG) < 7 mmol/l at 8 weeks. RESULTS: Ten men and 15 women (mean age 48, range 26-68 years) participated. Mean (sd) BMI was 34.2 kg/m2 (6.0); FPG 9.2 mmol/l (2.2). Mean weight loss at 8 weeks and 8 months was 10.1 kg [95% confidence interval (CI) 8.1, 12.0] and 8.2 kg (95% CI 5.8, 10.6); FPG was lower by 2.2 mmol/l (95% CI 1.2, 3.2) and 1.7 mmol/l (95% CI 0.8, 2.7) respectively. Nine of 11 (82%) of those who lost ≥ 10 kg were 'responders' compared with 6 of 14 (43%) who lost < 10 kg (P = 0.048). The 30-min insulin increment was higher in responders at baseline and follow-up (P ≤ 0.01). A food culture based on starchy foods and pressures to eat large amounts at social events were among the challenges identified by participants. CONCLUSIONS: The feasibility of this approach to weight loss and diabetes remission in a predominantly black population in Barbados was demonstrated.

IFN-γ induction by neutrophil-derived IL-17A homodimer augments pulmonary antibacterial defense.

The role of interleukin-17A (IL-17A) in host defense against Legionella pneumophila remains elusive. To address this issue, we used Il17a(-/-), Il17f(-/-), and Il17a/Il17f(-/-) mice on a C57Bl/6 (non-permissive) background and IL-17 neutralizing Abs in mice on an A/J (permissive) background. Higher bacterial (L. pneumophila) counts in the lung and blood along with reduced neutrophil recruitment were detected in Il17a(-/-), but not Il17f(-/-), mice. We found that neutrophils produce IL-17A homodimer (IL-17A) during L. pneumophila infection, and hematopoietic cell-derived IL-17A is known to be important for bacterial clearance. Thus, intratracheal administration of wild-type neutrophils or recombinant IL-17A restored bacterial clearance and neutrophil recruitment in Il17a(-/-) mice. Furthermore, neutrophil-depleted Rag2(-/-) and Rag2/Il-2rγ(-/-) mice exhibited increased bacterial burden, reduced neutrophil influx and IL-17A production in the lung. Recombinant IFN-γ administration in Il17a(-/-) mice augmented bacterial elimination, whereas IL-17A administration in Ifnγ(-/-) mice did not augment bacterial clearance. IFN-γ is produced by T cells, but not neutrophils or macrophages, suggesting that neutrophil-derived IL-17A induces IFN-γ in a paracrine fashion. Human pneumonic lungs and human neutrophils challenged with L. pneumophila exhibited increased numbers of IL-17A producing cells. These findings display a novel function of neutrophil-derived IL-17A in antibacterial defense via the induction of IFN-γ in a paracrine manner.

NLRP12 modulates host defense through IL-17A-CXCL1 axis.

We used an extracellular pathogen Klebsiella pneumoniae to determine the role of NLRP12 (NOD-like receptor (NLR) family pyrin domain containing 12) as this bacterium is associated with devastating pulmonary infections. We found that human myeloid cells (neutrophils and macrophages) and non-myeloid cells (epithelial cells) show upregulation of NLRP12 in human pneumonic lungs. NLRP12-silenced human macrophages and murine Nlrp12(-/-) macrophages displayed reduced activation of nuclear factor-κB and mitogen-activated protein kinase, as well as expression of histone deacetylases following K. pneumoniae infection. NLRP12 is important for the production of interleukin-1ß (IL-1ß) in human and murine macrophages following K. pneumoniae infection. Furthermore, host survival, bacterial clearance, and neutrophil recruitment are dependent on NLRP12 following K. pneumoniae infection. Using bone marrow chimeras, we showed that hematopoietic cell-driven NLRP12 signaling predominantly contributes to host defense against K. pneumoniae. Intratracheal administration of either IL-17A+ CD4 T cells or chemokine (C-X-C motif) ligand 1 (CXCL1+) macrophages rescues host survival, bacterial clearance, and neutrophil recruitment in Nlrp12(-/-) mice following K. pneumoniae infection. These novel findings reveal the critical role of NLRP12-IL-17A-CXCL1 axis in host defense by modulating neutrophil recruitment against this extracellular pathogen.

Crystal structure of 5-(1-benzo-furan-2-yl)-3-(4-methyl-phen-yl)-4,5-di-hydro-1,2-oxazol-5-ol.

In the title compound, C18H15NO3, the isoxazole moiety adopts a shallow envelope conformation, with the C atom bearing the OH group displaced by 0.148 (1) Šfrom the mean plane through the other four atoms. The mean plane of this ring (all atoms) subtends dihedral angles of 87.19 (6) and 15.51 (7)° with the benzo-furan ring system (r.m.s. deviation = 0.007 Å) and the 4-methylphenyl ring, respectively. In the crystal, mol-ecules are linked by O-H⋯N hydrogen bonds, generating [001] C(5) chains, with adjacent mol-ecules in the chain related by c-glide symmetry. Weak C-H⋯O inter-actions link the chains into a three-dimensional network.

Crystal structure of 1-benzyl-sulfonyl-1,2,3,4-tetra-hydro-quinoline.

In the title compound, C16H17NO2S, the heterocyclic ring adopts a half-chair conformation and the bond-angle sum at the N atom is 354.6°. The dihedral angle between the planes of the aromatic rings is 74.15 (10)°. In the crystal, mol-ecules are linked by weak C-H⋯O hydrogen bonds, generating C(8) and C(4) chains propagating along [100] and [010], respectively, which together generate (001) sheets.

Crystal structure of 1-[(6-chloro-pyridin-3-yl)sulfon-yl]-1,2,3,4-tetra-hydro-quinoline.

The tetra-hydro-pyridine ring of the quinoline system in the title compound, C14H13ClN2O2S, adopts a half-chair conformation with the bond-angle sum at the N atom being 350.0°. The dihedral angle between the least-squares planes of the two aromatic rings is 50.13 (11)°. In the crystal, inversion dimers linked by pairs of C-H⋯O hydrogen bonds generate R 2 (2)(10) loops. Additional inter-molecular C-H⋯O hydrogen bonds generate C(7) chains along [100].

Crystal structure of 1-methane-sulfonyl-1,2,3,4-tetra-hydro-quinoline.

In the title compound, C10H13NO2S, the heterocyclic ring adopts a half-chair conformation and the bond-angle sum at the N atom is 347.9°. In the crystal, inversion dimers linked by pairs of C-H⋯O hydrogen bonds generate R 2 (2)(8) loops.

Crystal structure of 1-tosyl-1,2,3,4-tetra-hydro-quinoline.

In the title compound, C16H17NO2S, the heterocyclic ring adopts a half-chair conformation and the bond-angle sum at the N atom is 350.2°. The dihedral angle between the planes of the aromatic rings is 47.74 (10)°. In the crystal, mol-ecules are linked by C-H⋯O hydrogen bonds to generate [010] chains.

2-(1,3-Benzodioxol-5-yl)-3-phenyl-quinazolin-4(3H)-one.

In the mol-ecule of the title compound, C21H14N2O3, the quinazoline ring system [maximum deviation = 0.076 (1) Å] makes dihedral angles of 40.57 (9) and 42.31 (11)°, respectively, with the phenyl and 1,3-benzodioxole rings. The dihedral angle between the phenyl ring and the 1,3-benzodioxole ring is 4.34 (10)°. In the crystal, C-H⋯O hydrogen bonds link the mol-ecules into infinite zigzag chains extending along [100].

5-{4'-[(5-Benzyl-2H-tetra-zol-2-yl)meth-yl]biphenyl-2-yl}-1H-tetra-zole monohydrate.

In the title compound, C22H18N8·H2O, the dihedral angle between the tetra-zole rings is 69.58 (1)° while the terminal phenyl ring makes dihedral angles of 26.98 (8) and 39.75 (8)° with the other benzene rings. The rings of the biphenyl unit subtend a dihedral angle of 55.23 (8)°. In the crystal, the solvent water mol-ecule is linked to the main mol-ecule via an N-H⋯O hydrogen bond. In addition, C-H⋯N and O-H⋯N hydrogen bonds link the components into chains along [010]. The crystal structure also features C-H⋯π and π-π inter-actions, with centroid-centroid distances of 3.6556 (9) and 3.826 (1) Å.

5-Methyl-3-phenyl-isoxazole-4-carb-oxy-lic acid.

In the title compound, C11H9NO3, the phenyl and isoxazole rings form a dihedral angle of 56.64 (8)°. The carb-oxy group is almost in the same plane as the isoxazole ring with a C-C-C-O torsion angle of -3.3 (2)°. In the crystal, pairs of O-H⋯O hydrogen bonds link the mol-ecules into head-to-head dimers. C-H⋯N hydrogen bonds and π-π stacking inter-actions between phenyl rings [centroid-centroid distance = 3.9614 (17)Å] link the dimers into a three-dimensional network.

Ethyl 5-methyl-3-phenyl-isoxazole-4-carboxyl-ate.

In the title compound, C13H13NO3, the dihedral angle between the phenyl and isoxazole rings is 43.40 (13)°. The eth-oxy-carbonyl group is rotated out of the plane of the isoxazole ring by 16.2 (13)°.

(4-Hy-droxy-3,5-di-methyl-phen-yl)(phen-yl)methanone.

In the mol-ecule of the title compound, C15H14O2, the dihedral angle between the benzene and phenyl rings is 61.27 (8)°. In the crystal, O-H⋯O and weak C-H⋯O hydrogen bonds link the mol-ecules into chains extending along the c-axis direction.

4-[(E)-(4-Fluoro-benzyl-idene)amino]-3-methyl-1H-1,2,4-triazole-5(4H)-thione.

In the asymmetric unit of the title compound, C(10)H(9)FN(4)S, there are two independent mol-ecules in which the dihedral angles between the 1,2,4-triazole and benzene rings are 36.85 (10) and 7.81 (10)°. In the crystal, N-H⋯S inter-actions link pairs of independent mol-ecules into dimers. There are also π-π inter-actions between the triazole and benzene rings of inversion-related pairs of the more planar mol-ecule [centroid-centroid distance = 3.6430 (13) Å].