A single-molecule with multiple investigations: Synthesis, characterization, computational methods, inhibitory activity against Alzheimer's disease, toxicity, and ADME studies.

This study reports a newly synthesized crystalline molecule with azomethine structure, (E)-1-(5-nitro-2-(piperidin-1-yl)phenyl)-N-(p-tolyl)methanimine, and its structural, spectral, topological, and electronic properties calculated by combined experimental and computational techniques. The study also presents the computational approaches to drug-like nature of the molecule. The main objective of this study is to determine the drug-like properties of the title compound and to demonstrate its acetylcholinesterase inhibitory activity for the cholinergic hypothesis of Alzheimer's disease. In this work, we synthesized the title molecule by the condensation reaction between an aromatic amine and an aldehyde and verified its molecular structure by spectroscopic techniques (X-ray, FTIR, and UV-Vis). The computational results of the title compound (MEP, FTIR, UV-Vis, FMOs, Mulliken charges, HOMO-LUMO analysis, structure optimization) were obtained at the DFT/B3LYP level using the Gaussian package program. In silico biological studies such as target identification, ADMET prediction, BBB permeation, gastrointestinal absorption, and molecular docking studies were performed using web tools or software: BindingDB, SwissTargetPrediction, admetSAR, ADMETlab, SwissADME, ProTox- II, BOILED -Egg method, and AutoDock. The ADME profile of the title compound is at the desired level and within the range of applicability. The compound was evaluated as mutagenic and carcinogenic in toxicity analyzes. The title compound can pass the BBB and be absorbed by the human gastrointestinal tract. The calculated docking score of the title compound is not better than the AChE inhibitors known as galantamine and donepezil (positive control group). The binding energies of the complexes, title compound-AChE, donepezil-AChE, and galantamine-AChE, were calculated to be -7.80, -10.41, and -8.16 kcal/mol, respectively.

Synthesis, characterization, computational analyses, in silico ADMET studies, and inhibitory action against SARS-CoV-2 main protease (Mpro) of a Schiff base.

COVID-19 disease caused by the severe acute respiratory syndrome coronavirus (SARS-CoV-2) has struck the whole world and raised severe health, economic, and social problems. Many scientists struggled to find a vaccine or an antiviral drug. Eventually, both vaccines and recommended drugs, repurposed drugs, or drug combinations were found, but new strains of SARS-CoV-2 continue to threaten human life and health. As part of the fight against COVID-19 disease, this study involves an in silico molecular docking analysis on the main protease (Mpro) of SARS-CoV-2. To this aim, a Schiff base compound was synthesized and characterized using spectroscopic techniques, including X-ray, FTIR, and UV-Vis. Surface analysis and electronic properties of this molecule were investigated using the DFT method. The drug-likeness parameters of the title compound were studied according to the rules of Lipinski, Veber, Ghose, Egan, and Muegge and were found in agreement with these rules. In silico toxicity analyses revealed that the new compound is a potentially mutagenic and carcinogenic chemical. The title compound was predicted to be an inhibitor of cytochrome P450 enzymes (5 CYPs). This inhibitory effect indicates a weak metabolism of the molecule in the liver. In addition, this compound was displayed good intestinal absorption and blood-brain barrier penetration. The druggability properties of the title compound were investigated, and SwissTargetPrediction predicted it to be a protease inhibitor. In this context, the SARS-CoV-2 main protease was selected as a biological target in molecular docking studies. Docking results were compared with the known native ligand N3 inhibitor. The value of binding energy between the Schiff base compound and the binding pocket of the main protease is higher than that of the reference ligand N3. The calculated free energies of binding of the Schiff base compound and the reference ligand N3 are -8.10 and -7.11 kcal/mol, respectively.

Effects of negative pressure wound therapy on an axial congested rabbit skin flap model without any bare surface.

One of the most important problems encountered in reconstructive surgery is partial or total flap loss, and venous congestion is the most common reason. It should be solved as early as possible. The purpose of this study is to investigate the effects of Negative pressure wound therapy (NPWT) on an ideal congested rabbit skin flap model without any open wound. The current study included 28 female, adult, New Zealand albino rabbits. Animals were divided into four groups according to the duration of NPWT to be applied. An axial pattern ideal congested skin flap was designed on the posterior surface of the ear. After surgical intervention on the right ears, we applied NPWT treatment for 2, 4, 6 and 8 days. The left ears were followed without any treatment. Samples were taken for edema, congestion and neo-angiogenesis examination. There was no significant difference between the NPWT applied group and control group in the 2nd, 4th, 6th, and 8th days for edema and neo-angiogenesis and no differences in the 2nd, 6th, and 8th days for congestion. NPWT group had a higher flap survival rate than the control group but without a significant difference. This study used an ideal congested rabbit skin flap model imitating venous congestion. Our findings illustrate that NPWT treatment does not have a significant effect on the congested skin flap model we utilized where a closed system was created maintaining a skin barrier without a bare surface of the flap. Level of Evidence: Level I, experimental study.

Adenocarcinoma in a Tailgut Cyst: A Rare Case Report.

Developmental cysts are the most common retrorectal area cysts observed in adults. Tailgut cysts tend to be multicystic, and their lining epithelium may display the characteristics of columnar, musin-secreting columnar, ciliated, transitional or squamous epithelia. While the large majority of cysts tend to be benign, several malignant cases have been reported, with adenocarcinoma and carcinoid tumors constituting the more common types of malignant tailgut cysts. A 55-year-old female patient presented to our hospital with complaints of swelling in the gluteal region. Following morphological, histomorphological and immunohistochemical evaluations, a diagnosis of a moderately differentiated adenocarcinoma arising from a tailgut cyst was made. Tailgut cysts are infrequent diseases but adenocarcinoma arising from a tailgut cyst is extremely rare. In rare cases, developmental cysts may undergo malignant transformation that warrants an accurate morphological and histomorphological assessment, as well as numerous samplings, for an accurate diagnosis.

A3B type unsymmetrical and amphiphilic phthalocyanines: Synthesis, characterization, thermal stability and aggregation studies.

This study reports the preparation, analysis, aggregation statuses and thermal properties of five phthalocyanines. The preparation of all molecules includes two steps: the first step is the preparation of phthalocyanine precursor molecules (A and B coded phthalonitriles); the second step is the synthesis of one metal-free and four metalled phthalocyanines (A3B-Co, A3B-Cu, A3B-H, A3B-Ni, and A3B-Zn coded compounds). Compound A holds a hydrophobic chain (cetyl alcohol); compound B holds a hydrophilic chain (tetraethylene glycol). Phthalocyanines include three hydrophobic chains and one hydrophilic chain (A3B type phthalocyanine). Characterization methods which were used to determine the structure of these compounds are Fourier Transform Infrared (FTIR), Proton Nuclear Magnetic Resonance (1H NMR), Carbon-13 Nuclear Magnetic Resonance (13C NMR), and Ultraviolet Visible (UV Vis) spectroscopies and elemental analysis. The phthalocyanines have high stability up to 260 °C as a minimum value. Aggregation statuses of the phthalocyanines change to the metal from the metal or to the solvent from the solvent.

Programmed Death-Ligand-1 Expression in Non-Small Cell Lung Cancer and Prognosis

Background: Prognostic significance of the programmed death-ligand-1 status in non-small cell lung carcinoma remains controversial. Aims: To show the programmed death-ligand-1 expression status in patients with non-small cell lung carcinoma and its effect on the prognosis and the relationship with clinicopathologic data. Study Design: Retrospective cross-sectional study. Methods: The study included 208 cases who were diagnosed with NSCLC and who underwent surgical resection between 2001 and 2012. Programmed death-ligand-1 (SP142 clone) was applied to the histological sections acquired from the microarray paraffin blocks with immunohistochemistry. Staining intensity was scored as weak (+, 1), moderate (++, 2), and strong (+++, 3). Percentage (0%-100%) was multiplied by staining intensity (1-2-3) to calculate the H score. Four different cut-off values were used; 1: ≥1% (independent of intensity), 2: ≥5% (independent of intensity), 3: ≥5% moderate/strong staining (except for weak staining), 4: H score ≥30 values were considered positive. In this study, staining a single cell at any intensity was considered positive. Results: Thirty-four out 208 cases (16.3%) had PDL-1 positive staining. PDL-1 expression was observed in patients with non-small cell lung carcinoma independent of the histological type or subtype (range; 0-25%). When the cut-off level was set to ≥5% with moderate and strong staining, the median overall survival was 45 months for the PD-L1 positive group and not reached for the PD-L1 negative group (p-value 0.024). PD-L1 positivity was significantly higher in patients over the age of 60 years and in cases with a tumor diameter of more than 5 cm (p=0.023 and 0.025, respectively). Conclusion: PD-L1 expression is positive in 16.3% of patients with non-small cell lung cancer and may have a negative prognostic value.

Crystal structure of 2-{[2-meth-oxy-5-(tri-fluoro-meth-yl)phen-yl]iminomethyl}-4-nitro-phenol.

In the title compound, C15H11F3N2O4, the N=C bond of the central imine group adopts an E conformation. The dihedral angle between two benzene rings is 6.2 (2)°. There is an intra-molecular bifurcated O-H⋯(N,O) hydrogen bond with S(6) and S(9) ring motifs. In the crystal, mol-ecules are linked by C-H⋯O hydrogen bonds into a helical chain along the 31 screw axis parallel to c. The -CF3 group shows rotational disorder over two sites, with occupancies of 0.39 (2) and 0.61 (2).

2-{[3-Chloro-4-(4-chloro-phen-oxy)phen-yl]imino-meth-yl}-4-nitro-phenol.

In the title compound, C19H12Cl2N2O4, the imine bond length of 1.257 (6) Šis typical of a double bond. The dihedral angle between the para-nitro benzene ring and the central benzene ring is 12.06 (3)° and that between the central benzene and the para-chloro benzene ring is 73.81 (2)°. An intra-molecular O-H⋯N hydrogen bond generates an S(6) ring motif. In the crystal, mol-ecules are linked together by two pairs of C-H⋯O interactions (to the same O atom acceptor), forming inversion dimers. A short Cl⋯Cl contact [3.232 (4) Å] is observed.

Oral manifestations may be the first sign of Langerhans cell histiocytosis.

Langerhans cell histiocytosis (LCH) is a rare proliferative disorder of histiocytes characterised by a proliferation of abnormal and clonal Langerhans cells. LCH most commonly occurs as a localised solitary bone lesion and appears predominantly in paediatric patients. This case report presents clinicopathological features of this disorder in a 2-year-old boy. The presenting features of the patient included fever, bleeding gums and seborrheic dermatitis-like rash. Intraoral examination and radiographs revealed deep pockets and severe bone loss around all primary molars. Due to severe periodontal destruction, a gingival biopsy was taken. The biopsy specimen revealed heavy infiltration of Langerhans histiocytes. Chemotherapy was administered. Although no clear cause of LCH has been identified, the disease can be triggered by environmental agents and viruses, in particular Epstein-Barr virus. Oral manifestations may be the first or only signs of LCH.

Ni(II)-tetrahedral complexes: characterization, antimicrobial properties, theoretical studies and a new family of charge-transfer transitions.

A new amine containing selenium and their five imine, (SeSchX)(X: -H, F, Cl, Br, CH3), and Ni (II) complexes, [Ni(SeSchX)(H2O)2]Cl/[Ni(SeSchCl)(H2O)Cl], were synthesized. The compounds were characterized by means of elemental analyses, (13)C and (1)H NMR (for imine), FT-IR, UV-Visible spectroscopy, TGA/DTA and elemental analyses. [Ni(SeSchCl)(H2O)Cl] complex from Ni(II) complexes changes color from yellow to orange in the range pH 5-7. [Ni(SeSchCl)(H2O)Cl] complex has ligand-to-metal charge-transfer (LMCT) transitions in the basic medium. Excitation characteristics and energetic of [Ni(SeSchCl)(H2O)Cl] complex, examined via TD-DFT calculations, reveals transitions of LMCT and π→π(*) character that matches the experimental values. [Ni(SeSchCl)(H2O)Cl] complex showed the highest antibacterial activity when compared to other complexes reported in this work.