Crystal structure to 2.45 A resolution of a monoclonal Fab specific for the Brucella A cell wall polysaccharide antigen.

The atomic structure of an antibody antigen-binding fragment (Fab) at 2.45 A resolution shows that polysaccharide antigen conformation and Fab structure dictated by combinatorial diversity and domain association are responsible for the fine specificity of the Brucella-specific antibody, YsT9.1. It discriminates the Brucella abortus A antigen from the nearly identical Brucella melitensis M antigen by forming a groove-type binding site, lined with tyrosine residues, that accommodates the rodlike A antigen but excludes the kinked structure of the M antigen, as envisioned by a model of the antigen built into the combining site. The variable-heavy (VH) and variable-light (VL) domains are derived from genes closely related to two used in previously solved structures, M603 and R19.9, respectively. These genes combine in YsT9.1 to form an antibody of totally different specificity. Comparison of this X-ray structure with a previously built model of the YsT9.1 combining site based on these homologies highlights the importance of VL:VH association as a determinant of specificity and suggests that small changes at the VL:VH interface, unanticipated in modeling, may cause significant modulation of binding-site properties.     

Comparative bioinformatics analysis and abiotic stress responses of expansin proteins in Cucurbitaceae members: watermelon and melon

Protoplasma - Watermelon and melon are members of the Cucurbitaceae family including economically significant crops in the world. The expansin protein family, which is one of the members of the...     

Effect of Axial Ligand Length on Biological and Anticancer Properties of Axially Disubstituted Silicon Phthalocyanines

In this study, three new axially disubstituted silicon phthalocyanines ( SiPc1–3 ) and their quaternized phthalocyanine derivatives ( QSiPc1–3 ) were prepared and characterized. The biological properties (antioxidant, antimicrobial, antibiofilm, and microbial cell viability activities) of the water-soluble silicon phthalocyanines were examined, as well. A 1 % DMSO diluted with pure water was used as a solvent in biological activity studies. All the compounds exhibited high antioxidant activity. They displayed efficient antimicrobial and antimicrobial photodynamic therapeutic properties against various microorganisms, especially Gram (+) bacteria. Additionally, they demonstrated high antibiofilm activities against S. aureus and P. aeruginosa. In addition, 100 % bacterial reduction was obtained for all the studied phthalocyanines against E. coli viable cells. Besides, the DNA cleavage and binding features of compounds ( QSiPc1–3 ) were studied using pBR322 DNA and CT-DNA, respectively. Furthermore, the human topoisomerase I enzyme inhibition activities of compounds QSiPc1 – 3 were studied. Anticancer properties of the water-soluble compounds were investigated using cell proliferation MTT assay. They exhibited anticarcinogenic activity against the human colon cancer cell line (DLD-1). Compounds QSiPc1 and QSiPc3 displayed a high anticarcinogenic effect on the DLD-1 cell line. The obtained results indicated that all the studied compounds may be effective biological agents and anticancer drugs after further investigations.     

Structure-Activity Relationship of Methyl 4-Aminobenzoate Derivatives as Being Drug Candidate Targeting Glutathione Related Enzymes: in Vitro and in Silico Approaches

A thiol compound, glutathione, is essential for healthy cell defence against xenobiotics and oxidative stress. Glutathione reductase (GR) and glutathione S-transferase (GST) are two glutathione-related enzymes that function in the antioxidant and the detoxification systems. In this study, potential inhibitory effects of methyl 4-aminobenzoate derivatives on GR and GST were examined in vitro. GR and GST were isolated from human erythrocytes with 7.63 EU/mg protein and 5.66 EU/mg protein specific activity, respectively. It was found that compound 1 (methyl 4-amino-3-bromo-5-fluorobenzoate with K_i value of 0.325±0.012 μM) and compound 5 (methyl 4-amino-2-nitrobenzoate with K_i value of 92.41±22.26 μM) inhibited GR and GST stronger than other derivatives. Furthermore, a computer-aided method was used to predict the binding affinities of derivatives, ADME characteristics, and toxicities. Derivatives 4 (methyl 4-amino-2-bromobenzoate) and 6 (methyl 4-amino-2-chlorobenzoate) were estimated to have the lowest binding energies into GR and GST receptors, respectively according to results of in silico studies.     

Fluorinated Phthalocyanine/Silver Nanoconjugates for Multifunctional Biological Applications

In this study, a new phthalonitrile derivative namely 4-[(2,4-difluorophenyl)ethynyl]phthalonitrile ( 1 ) and its metal phthalocyanines ( 2 and 3 ) were synthesized. The resultant compounds were conjugated to silver nanoparticles and characterized using transmission electron microscopy (TEM) images. The biological properties of compounds ( 1 – 3 ), their nanoconjugates ( 4 – 6 ), and silver nanoparticles ( 7 ) were examined for the first time in this study. The antioxidant activities of biological candidates ( 1 – 7 ) were studied by applying the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay. The highest antioxidant activity was obtained 97.47 % for 200 mg/L manganese phthalocyanine-silver nanoconjugates ( 6 ). The antimicrobial and antimicrobial photodynamic therapy (APDT) activities of biological candidates ( 1 – 7 ) were examined using a micro-dilution assay. The highest MIC value was obtained 8 mg/L for nanoconjugate 6 against E. hirae. The studied compounds and their silver nanoconjugates exhibited high APDT activities against all the studied microorganisms. The most effective APDT activities were obtained 4 mg/L for nanoconjugates ( 5 and 6 ) against L. pneumophila and E. hirae, respectively. All the studied biological candidates displayed high cell viability inhibition activities against E. coli cell growth. The biofilm inhibition activities of the tested biological candidates were also investigated against S. aureus and P. Aeruginosa. Biological candidates ( 1 – 6 ) can be considered efficient metal nanoparticle-based materials for multi-disciplinary biological applications.     

HPLC-DAD Analysis and Versatile Bioactivities of Turkish Sunflower Honeys Using Chemometric Approaches

Sunflower honey (SH) is bright yellow, fragrant, pollen-flavoured, slightly herbaceous and has a unique taste. The present research aims to examine the enzyme inhibitory, antioxidant, anti-inflammatory, antimicrobial and anti-quorum sensing activities and phenolic compositions of 30 sunflower honeys (SHs) produced from several regions of Turkey with chemometric study. SAH from Samsun exhibited the best antioxidant activity in β-carotene linoleic acid (IC₅₀: 7.33±0.17 mg/mL) and CUPRAC (A_0.50: 4.94±0.13 mg/mL) assays, anti-urease activity (60.63±0.87 %) and anti-inflammatory activity against COX-1 (73.94±1.08 %) and COX-2 (44.96±0.85 %). SHs exhibited mild antimicrobial activity against the test microorganisms while they showed high quorum sensing inhibition zones measured in the range of 42–52 mm against the CV026 strain. The phenolic composition was determined by high performance liquid chromatography with diode array detection (HPLC-DAD) system and levulinic, gallic, p-hydroxybenzoic, vanillic and p-coumaric acids were identified in all studied SHs. The classification of SHs was performed the using PCA and HCA. This study revealed that phenolic compounds and biological properties are effective in classification of SHs according to their geographical origin. The results suggest that studied SHs could be valued as potential agents with versatile bioactivities in oxidative stress-related disease, microbial infections, inflammation, melanoma, and peptic ulcer.     

Evaluation of Acetic Acid-Induced Chronic Gastric Ulcer Healing by Propionyl-L-Carnitine Administration

The aim of our study was to investigate the healing effect of propionyl-L-carnitine (PLC) on chronic gastric ulcers and its underlying mechanisms. This study included rats with gastric ulcers induced by applying serosal glacial acetic acid. These rats were then given either saline (vehicle) or PLC at doses of 60 and 120 mg/kg, administered orally 3 days after ulcer induction for 14 consecutive days. Our study found that treatment with PLC resulted in a reduction of the gastric ulcer area, a faster rate of ulcer healing, and stimulated mucosal restoration. Additionally, the treatment with PLC reduced the number of Iba-1+ M1 macrophages while increasing the number of galectin-3+ M2 macrophages, as well as desmin+ microvessels, and α-SMA+ myofibroblasts in the gastric ulcer bed. The mRNA expression of COX-2, eNOS, TGF-β1, VEGFA, and EGF in the ulcerated gastric mucosa was greater in the PLC-treated groups compared with the vehicle-treated rats. In conclusion, these findings suggest that PLC treatment may accelerate gastric ulcer healing by stimulating mucosal reconstruction, macrophage polarization, angiogenesis, and fibroblast proliferation, as well as fibroblast-myofibroblast transition. This process is associated with the upregulation of TGF-β1, VEGFA, and EGF, as well as modulation of the cyclooxygenase/nitric oxide synthase systems.     

High-Resolution Performance of Polycaprolactone Functionalized with Guanidinium Ionic Liquid for Gas Chromatography

This work firstly reported a new polycaprolactone based material functionalized with guanidinium ionic liquid (PCL-GIL) as the stationary phase with high resolution performance for capillary gas chromatography (GC). It is composed of polycaprolactone (PCL) and guanidinium ionic liquid (GIL) with amphiphilic conformation. The PCL-GIL capillary column coated by static method exhibited high column efficiency of 3942 plates/m and moderate polarity. As a result, the PCL-GIL column exhibited high-resolution capability. For a mixture of 27 analytes with a wide ranging polarity and outperformed the PCL-2OH and HP-35 columns, showing its advantageous separation capability for analytes of diverse types. Moreover, the PCL-GIL column showed high resolving capability for various positional isomers and cis-/trans-isomers, including alkylbenzenes, chlorobenzenes, naphthalenes, bromonitrobenzenes, chloronitrobenzenes, benzaldehydes, phenols, alcohols, respectively. In a word, PCL derivatized by GIL units as a new type of stationary phase has a promising future in GC separations.     

Design,in Silico Studies and Biological Evaluation of New Chiral Thiourea and 1,3-Thiazolidine-4,5-dione Derivatives

In this study, new chiral thiourea and 1,3-thiazolidine-4,5-dione derivatives were synthesized, it was aimed to evaluate the various biological activities and molecular docking of these compounds. Firstly, the new thioureas ( 1 – 16 ) were obtained by reacting 1-naphthylisothiocyanate with different chiral amines. Then, the chiral thioureas were cyclized with oxalyl chloride to obtain 1,3-thiazolidine-4,5-dione derivatives ( 17 – 32 ). All compounds were evaluated with several in vitro antioxidant and enzyme inhibition activities. Compound 30 was the most active compound against AChE, with a value of IC₅₀=8.09±0.58 μM. On the other hand, all compounds were tested in silico absorption, distribution, metabolism, and excretion (ADME) assays to better understand their bioavailability. These physicochemical properties, pharmacokinetics, and drug-likeness of all compounds were calculated using SwissADME. Furthermore, according to molecular docking analyses compound 30 exhibited significant binding affinities for all enzymes. Based on our overall observations, compound 30 could be recommended as a potential lead for the therapuetic of Alzheimer's.     

Synthesis of Schiff Bases and Secondary Amines with Indane Skeleton; Evaluation of Their Antioxidant,Antibiotic, and Antifungal Activities

In this study, Schiff bases were synthesized by utilizing the reaction of 4- and 5-aminoindane with substituted benzaldehydes. After the reduction of isolated Schiff bases with NaBH₄, the corresponding secondary amine derivatives were obtained. The structures of all synthesized molecules were confirmed by ¹H-NMR, ¹³C-NMR, FT-IR, and ESI-MS. Antioxidant activities of all synthesized molecules were investigated by DPPH method, and IC₅₀ values were calculated. In addition, antibacterial activities of targets were investigated by the well diffusion method, and then MIC99 values were calculated. While only four of the sixteen synthesized molecules showed a high level of antioxidant activity, all of the molecules exhibited biological activity against Gram-positive and Gram-negative bacteria to varying degrees. In addition, all the synthesized molecules showed high antifungal activity. In antioxidant capacity studies, the IC₅₀ values of 2-(((2,3-dihydro-1H-inden-5-yl)amino)methyl)-6-methoxyphenol ( 4 d ) and 2-(((2,3-dihydro-1H-inden-4-yl)amino)methyl)-6-methoxyphenol ( 7 d ) were determined to be 18.1 μg and 35.1 μg, respectively, and these values are much stronger than BHT (butylated hydroxytoluene) and BHA (butylated hydroxyanisole) used as positive controls. The fact that targets have the same core structure with different substituents has revealed a good structure-activity relationship.