Hindering the biofilm of microbial pathogens and cancer cell lines development using silver nanoparticles synthesized by epidermal mucus proteins from Clarias gariepinus.

Scientists know very little about the mechanisms underlying fish skin mucus, despite the fact that it is a component of the immune system. Fish skin mucus is an important component of defence against invasive infections. Recently, Fish skin and its mucus are gaining interest among immunologists. Characterization was done on the obtained silver nanoparticles Ag combined with Clarias gariepinus catfish epidermal mucus proteins (EMP-Ag-NPs) through UV-vis, FTIR, XRD, TEM, and SEM. Ag-NPs ranged in size from 4 to 20 nm, spherical in form and the angles were 38.10°, 44.20°, 64.40°, and 77.20°, Where wavelength change after formation of EMP-Ag-NPs as indicate of dark brown, the broad band recorded at wavelength at 391 nm. Additionally, the antimicrobial, antibiofilm and anticancer activities of EMP-Ag-NPs was assessed. The present results demonstrate high activity against unicellular fungi C. albicans, followed by E. faecalis. Antibiofilm results showed strong activity against both S. aureus and P. aeruginosa pathogens in a dose-dependent manner, without affecting planktonic cell growth. Also, cytotoxicity effect was investigated against normal cells (Vero), breast cancer cells (Mcf7) and hepatic carcinoma (HepG2) cell lines at concentrations (200-6.25 µg/mL) and current results showed highly anticancer effect of Ag-NPs at concentrations 100, 5 and 25 µg/mL exhibited rounding, shrinkage, deformation and granulation of Mcf7 and HepG2 with IC50 19.34 and 31.16 µg/mL respectively while Vero cells appeared rounded at concentration 50 µg/mL and normal shape at concentration 25, 12.5 and 6.25 µg/ml with IC50 35.85 µg/mL. This study evidence the potential efficacy of biologically generated Ag-NPs as a substitute medicinal agent against harmful microorganisms. Furthermore, it highlights their inhibitory effect on cancer cell lines.

Gamma radiation-induced grafting of poly(butyl acrylate) onto ethylene vinyl acetate copolymer for improved crude oil flowability.

Ethylene vinyl acetate (EVA) copolymers are widely employed as pour point depressants to enhance the flow properties of crude oil. However, EVA copolymers have limitations that necessitate their development. This work investigated the modification of EVA via gamma radiation-induced grafting of butyl acrylate (BuA) monomers and the evaluation of grafted EVA as a pour point depressant for crude oil. The successful grafting of poly(butyl acrylate) p(BuA) onto EVA was verified through grafting parameters, FTIR spectroscopy, and 1H NMR spectroscopy. Treating crude oil with 3000 ppm of (EVA)0kGy, (EVA)50kGy, and (1EVA:3BuA)50kGy yielded substantial reductions in pour point of 24, 21, and 21 °C, respectively. Also, rheological characterization demonstrated improving evidenced by a viscosity reduction of 76.20%, 67.70%, and 71.94% at 25 °C, and 83.16%, 74.98%, and 81.53% at 12 °C. At low dosages of 1000 ppm, the EVA-g-p(BuA) exhibited superior pour point reductions compared to unmodified EVA, highlighting the benefit of incorporating p(BuA) side chains. The grafted EVA copolymers with p(BuA) side chains showed excellent potential as crude oil flow improvers by promoting more effective adsorption and co-crystallization with paraffin wax molecules.

2-Thioxo-3,4-dihydropyrimidine and thiourea endowed with sulfonamide moieties as dual EGFRT790M and VEGFR-2 inhibitors: Design, synthesis, docking, and anticancer evaluations.

The effectiveness of a new series of thiopyrimidine and thiourea containing sulfonamides moieties was tested on HCT-116, MCF-7, HepG2, and A549. HepG2 cell line was the one that all the new derivatives affected the most. The greatest potent compounds against the four HepG2, HCT116, MCF-7, and A549 cell lines were 8f and 8g with IC50 = 4.13, 6.64, 5.74, 6.85 µM and 4.09, 4.36, 4.22, 7.25 µM correspondingly. Compound 8g exhibited higher activity than sorafenib against HCT116 and MCF-7 but exhibited lower activity against HepG2 and A549. Moreover, compounds 8f and 8g exhibited higher activities than erlotinib on HepG2, HCT116, and MCF-7 but demonstrated lower activity on A549. The most potent cytotoxic derivatives 6f, 6g, 8c, 8d, 8e, 8f, and 8g were examined on normal VERO cell lines. Our derivatives have low toxicity on VERO cells with IC50 values ranging from 32.05 to 53.15 µM. Additionally, all compounds were assessed for dual VEGFR-2 and EGFRT790M inhibition effects. Compounds 8f and 8g were the most potent derivatives inhibited VEGFR-2 at IC50 value of 0.88 and 0.90 µM, correspondingly. As well, derivatives 8f and 8g could inhibit EGFRT790M demonstrating strongest effects with IC50 = 0.32 and 0.33 µM sequentially. Additionally, the greatest active derivatives ADMET profile was evaluated in relationship with sorafenib and erlotinib as reference agents. The data attained from docking were greatly related to that achieved from the biological testing.

Geotechnical and environmental radioactivity investigations at Al Sadis Min Uktober city, Cairo municipality (Egypt), for the high-speed railway construction.

The present study aims to evaluate the possibility of constructing a new high-speed railway (HSR) at Al Sadis Min Uktober city, Cairo (Egypt): geotechnical and environmental radiological hazards are estimated from several collected soil and water samples. A variety of laboratory geotechnical tests such as grain size, free swelling test, liquid and plastic limits, chemical analysis and uniaxial compression strength are applied to sixty-one drill holes. A geotechnical examination of the coarse-grained soil at the foundation level classified it as poorly graded soil. The results of the investigation of fine-grained soil at the foundation level shown that the liquid limit ranges from 22% to 55%, the plastic limit ranges from 12% to 28%, the plasticity index varies from 11% to 33%, free swelling varies from 51% to 71%. Mechanically, the uniaxial compressive strength values on rock samples range from 6.96 MPa to 142.39 MPa. The radioactive study is performed to detect the 226Ra, 232Th, and 40 K activity concentrations of the soil samples: their mean values are 34 ± 10 Bq·kg-1, 14 ± 5 Bq·kg-1 and 552 ± 20 Bq·kg-1, respectively. The values of radiological hazard indexes are not exceeded the permissible limits: e.g. the mean value of absorbed dose rate is 47 ± 6 nGy h-1; the annual gonadal dose equivalent is 0.3 ± 0.04 mSv·y-1; the lifetime cancer risk is 02 ± 0.2·10-3. Thus, the soil in the studied railway area is safe to use in building materials and infrastructure applications: the radiological hazards and the geotechnical studies confirmed the studied area is suitable to construct a new community having a HSR. According to the SWOT-PEST and environmental impact analyses, the construction of the HSR meets the criteria of the Kyoto Protocol, the EU Climate and Energy policy, and other international treaties.

Synthesis, characterization, in silico molecular docking, and antibacterial activities of some new nitrogen-heterocyclic analogues based on a p-phenolic unit.

Nitrogen-containing heterocycles have shown pharmacological properties against various diseases. Herein, in our study, flavoHB enzyme is a highly promising well-validated target for identification of antibacterial inhibitors using in silico and in vitro techniques. To identify a new class of antimicrobial agents, N-(4-hydroxyphenyl)-3-oxobutanamide was utilized as a precursor in the synthesis of several nitrogen-based heterocycles (pyridine, pyrimidine, and pyrazole) attached to p-phenolic substrates 2-8. Treatment of 3-oxobutanimide 1 with malononitrile and/or ethyl cyanoacetate in ethanolic piperidine afforded the pyridinone analogues 2a,b. On the other hand, treatment of 1 with arylidene cyanothioacetamide furnished the pyridinthione derivative 3. The reaction of starting material 1 with salicylaldehyde and/or dimethyl formamide dimethyl acetal (DMF-DMA) yielded the pyridinones 4 and 5, respectively. Reaction of 1 with terephthalaldehyde and urea or thiourea gave bis structures 6a,b. The reaction of compound 1 with ethyl isothiocyanate and hydrazine hydrate afforded pyrimidine and pyrazole derivatives 7 and 8, respectively. The structures of newly prepared compounds 2-8 were elucidated using elemental data and spectral analyses such as IR, 1H NMR, 13C NMR, and MS. In addition, an in-house nitrogen-containing heterocycle analogues library 2-8 was examined and screened in vitro for their antibacterial effects against Gram-negative bacteria, Escherichia coli and Gram-positive bacteria, Staphylococcus haemolyticus, Kocuria kristinae, Enterococcus casseliflavus, and Bacillus cereus. Compounds 6a and 6b have also shown the highest antibacterial activity against all types of bacteria strains tested except Kocuria kristinae. Further, the molecular docking study of the newly prepared compounds with the target enzyme flavohemoglobin (flavoHB) was undertaken to explore their potential inhibitory activities. The results of the docking study indicated that compounds 6a and 6b have exerted the highest docking scores against the active site of flavoHB. As a result, the in vitro and molecular docking study findings suggested that the compounds 6a and 6b (with pyrimidine moiety, amide linkage, and phenolic substrate) might be potent bacterial flavohemoglobin (flavoHB) inhibitors and they could set a promising starting point for future design of antibacterial agents.

Eco-Friendly Synthesis, Biological Evaluation, and In Silico Molecular Docking Approach of Some New Quinoline Derivatives as Potential Antioxidant and Antibacterial Agents.

A new series of quinoline derivatives 5-12 were efficiently synthesized via one-pot multicomponent reaction (MCR) of resorcinol, aromatic aldehydes, ß-ketoesters, and aliphatic/aromatic amines under solvent-free conditions. All products were obtained in excellent yields, pure at low-cost processing, and short time. The structures of all compounds were characterized by means of spectral and elemental analyses. In addition, all the synthesized compounds 5-12 were in vitro screened for their antioxidant and antibacterial activity. Moreover, in silico molecular docking studies of the new quinoline derivatives with the target enzymes, human NAD (P)H dehydrogenase (quinone 1) and DNA gyrase, were achieved to endorse their binding affinities and to understand ligand-enzyme possible intermolecular interactions. Compound 9 displayed promising antioxidant and antibacterial activity, as well as it was found to have the highest negative binding energy of -9.1 and -9.3 kcal/mol for human NAD (P)H dehydrogenase (quinone 1) and DNA gyrase, respectively. Further, it complied with the Lipinski's rule of five, Veber, and Ghose. Therefore, the quinoline analogue 9 could be promising chemical scaffold for the development of future drug candidates as antioxidant and antibacterial agents.

Multifunctional Isosteric Pyridine Analogs-Based 2-Aminothiazole: Design, Synthesis, and Potential Phosphodiesterase-5 Inhibitory Activity.

The elaboration of new small molecules that target phosphodiesterase enzymes (PDEs), especially those of type 5 (PDE5), is an interesting and emerging topic nowadays. A new series of heterocycle-based aminothiazoles were designed and synthesized from the key intermediate, 3-oxo-N-(thiazol-2-yl)butanamide (a PDE5 inhibitor that retains its amidic function), as an essential pharmacophoric moiety. The PDE5 inhibitors prevent the degradation of cyclic guanosine monophosphate, thereby causing severe hypotension as a marked side effect. Hence, an in vivo testing of the target compounds was conducted to verify its relation with arterial blood pressure. Utilizing sildenafil as the reference drug, Compounds 5, 10a, and 11b achieved 100% inhibitions of PDE5 without significantly lowering the mean arterial blood pressures (115.95 ± 2.91, 110.3 ± 2.84, and 78.3 ± 2.57, respectively). The molecular docking study revealed that the tested compounds exhibited docking poses that were similar to that of sildenafil (exploiting the amide functionality that interacted with GLN:817:A). The molecular shape and electrostatic similarity revealed a comparable physically achievable electrostatic potential with the reference drug, sildenafil. Therefore, these concomitant results revealed that the tested compounds exerted sildenafil-like inhibitory effects (although without its known drawbacks) on blood circulation, thus suggesting that the tested compounds might represent a cornerstone of beneficial drug candidates for the safe treatment for erectile dysfunction.

Design, synthesis and biological evaluation of new 2-aminothiazole scaffolds as phosphodiesterase type 5 regulators and COX-1/COX-2 inhibitors.

A new series of 2-aminothiazole derivatives was designed and prepared as phosphodiesterase type 5 (PDE5) regulators and COX-1/COX-2 inhibitors. The screening of the synthesized compounds for PDE5 activity was carried out using sildenafil as a reference drug. Strikingly, compounds 23a and 23c were found to have a complete inhibitory effect on PDE5 (100%) at 10 µM without causing hypotension and the limited side effect of PDE5 inhibitors, suggest a distinctive therapeutic role of these derivatives in erectile dysfunction. On the other hand, compounds 5a, 17, 21 and 23b increased the PDE5 activity (PDE5 enhancers) at 10 µM. In addition, the study includes the screening of the COX-1/COX-2 inhibition induced by the synthesized compounds. All tested compounds have an inhibitory effect against COX-1 activity (IC50 = 1.00-6.34 µM range) and COX-2 activity (IC50 = 0.09-0.71 µM range). Moreover, a molecular docking study was implemented to reveal the binding interactions of potent compounds in the binding sites of PDE5 (PDB ID 2H42), COX-1 and COX-2 (PDB ID 3LN1) enzymes. For the interaction with the PDE5 enzyme, activator compounds had a strong binding mode (HB with Gln817:A) than inhibitory derivatives. Both types of compounds are considered as PDE5 regulators. This novel finding will encourage us to discover a new pharmacological application of small chemical entities as the PDE5 enhancer, or will lower side effects as PDE5 inhibitors. All active compounds adopted the Y-shape along the COX-2 active site.

Multifunctional Magnetic Nanowires: Design, Fabrication, and Future Prospects as Cancer Therapeutics.

Traditional cancer therapeutics are limited by factors such as multi-drug resistance and a plethora of adverse effect. These limitations need to be overcome for the progression of cancer treatment. In order to overcome these limitations, multifunctional nanosystems have recently been introduced into the market. The employment of multifunctional nanosystems provide for the enhancement of treatment efficacy and therapeutic effect as well as a decrease in drug toxicity. However, in addition to these effects, magnetic nanowires bring specific advantages over traditional nanoparticles in multifunctional systems in terms of the formulation and application into a therapeutic system. The most significant of which is its larger surface area, larger net magnetic moment compared to nanoparticles, and interaction under a magnetic field. This results in magnetic nanowires producing a greater drug delivery and therapeutic platform with specific regard to magnetic drug targeting, magnetic hyperthermia, and magnetic actuation. This, in turn, increases the potential of magnetic nanowires for decreasing adverse effects and improving patient therapeutic outcomes. This review focuses on the design, fabrication, and future potential of multifunctional magnetic nanowire systems with the emphasis on improving patient chemotherapeutic outcomes.

Structural consideration of the formation of the activation complex between the staphylokinase-like streptococcal plasminogen activator PadA and bovine plasminogen.

The characteristics of a streptococcal plasminogen activator (PA) displaying specificity for ruminant plasminogen (Plg) were defined using molecular approaches. The 16-kDa secreted protein PadA was found to be prevalent in Streptococcus dysgalactiae subspecies dysgalactiae isolated from cases of bovine mastitis and septic arthritis in lambs. PadA was able to activate bovine, ovine and caprine Plg, but not human Plg. Amino acid sequence analysis identified a limited level of homology to other streptococcal PAs, including streptokinase; however, PadA was found to align well with and match in size the staphylococcal PA, staphylokinase. Recombinant PadA was used to investigate interaction with bovine Plg, leading to formation of an activator complex that was capable of recruiting and converting further substrate Plg into plasmin. Individual non-overlapping peptides of PadA or bovine microplasminogen were found to block the interaction between PadA and bovine Plg, preventing the formation of the activation complex. Homology modelling based upon structures of staphylokinase complexed with human microplasminogen supported these findings by placing critical residues in close proximity to the plasmin component of the activation complex.

Active membrane transport and receptor proteins from bacteria.

A general strategy for the expression of bacterial membrane transport and receptor genes in Escherichia coli is described. Expression is amplified so that the encoded proteins comprise 5-35% of E. coli inner membrane protein. Depending upon their topology, proteins are produced with RGSH6 or a Strep tag at the C-terminus. These enable purification in mg quantities for crystallization and NMR studies. Examples of one nutrient uptake and one multidrug extrusion protein from Helicobacter pylori are described. This strategy is successful for membrane proteins from H. pylori, E. coli, Enterococcus faecalis, Bacillus subtilis, Staphylococcus aureus, Microbacterium liquefaciens, Brucella abortus, Brucella melitensis, Campylobacter jejuni, Neisseria meningitides, Streptomyces coelicolor and Rhodobacter sphaeroides.

Regulation of anaerobic arginine catabolism in Bacillus licheniformis by a protein of the Crp/Fnr family.

Arginine anaerobic catabolism occurs in Bacillus licheniformis through the arginine deiminase pathway, encoded by the gene cluster arcABDC. We report here the involvement of a new protein, ArcR, in the regulation of the pathway. ArcR is a protein of the Crp/Fnr family encoded by a gene located 109 bp downstream from arcC. It binds to a palindromic sequence, very similar to an Escherichia coli Crp binding site, located upstream from arcA. Residues in the C-terminal domain of Crp that form the DNA binding motif, in particular residues Arg-180 and Glu-181 that make specific bonds with DNA, are conserved in ArcR, suggesting that the complexes formed with DNA by Crp and ArcR are similar. Moreover, the pattern of DNase I hypersensitivity sites induced by the binding of ArcR suggests that ArcR bends the DNA in the same way as Crp. From the absence of anaerobic induction following inactivation of arcR and from the existence of a binding site upstream of the arcA transcription start point, it can be inferred that ArcR is an activator of the arginine deiminase pathway.