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Colistin (polymyxin E) is a bactericidal antibiotic used to treat severe infections caused by multidrug-resistant Gram-negative bacteria. The product of theTwenty-seven bacterial isolates were collected from patients who were admitted to the National Cancer Institute, Cairo, Egypt, and processed using standard microbiological methods. Essential oils were purchased from AB Chem Company, Egypt, screened for antibacterial, cytotoxic activity, and (GC-MS) analysis.A total of 5 bacterial isolates were resistant to colistin with minimum inhibitory concentration (MIC) ranging from 6.25-200 µg/ml. Cinnamon oil exhibited the highest activity against colistin-resistant strains followed by thyme and eucalyptus oil. The (MIC) of cinnamon oils against resistant strains ranged from 4.88 to 312.5 µg/ml. Moreover, mcr-1 gene expression was extremely down-regulated after the treatment of bacterial strains with cinnamon oil and decreased to 20-35-fold. Examination of treated bacterial cells with sub-inhibitory concentrations under transmission electron microscopy showed various abnormalities occurred in most of these cells.Cinnamon oil exhibits antibacterial activity against colistin-resistant strains, showing it as a promising natural alternative in clinical therapy.

Purpose This study aims to focus on the preparation and characterization of the silver nanowire (AgNWs), as well as their application as antimicrobial and antivirus activities either with incorporation on the waterborne coating formulation or on their own. Design/methodology/approach Prepared AgNWs are characterized by different analytical instruments, such as ultraviolet-visible spectroscope, scanning electron microscope and X-ray diffraction spectrometer. All the paint formulation's physical and mechanical qualities were tested using American Society for Testing and Materials, a worldwide standard test procedure. The biological activities of the prepared AgNWs and the waterborne coating based on AgNWs were investigated. And, their effects on pathogenic bacteria, antioxidants, antiviral activity and cytotoxicity were also investigated. Findings The obtained results of the physical and mechanical characteristics of the paint formulation demonstrated the formulations' greatest performance, as well as giving good scrub resistance and film durability. In the antimicrobial activity, the paint did not have any activity against bacterial pathogen, whereas the AgNWs and AgNWs with paint have similar activity against bacterial pathogen with inhibition zone range from 10 to 14 mm. The development of antioxidant and cytotoxicity activity of the paint incorporated with AgNWs were also observed. The cytopathic effects of herpes simplex virus type 1 (HSV-1) were reduced in all three investigated modes of action when compared to the positive control group (HSV-1-infected cells), suggesting that these compounds have promising antiviral activity against a wide range of viruses, including DNA and RNA viruses. Originality/value The new waterborne coating based on nanoparticles has the potential to be promising in the manufacturing and development of paints, allowing them to function to prevent the spread of microbial infection, which is exactly what the world requires at this time.

Fungal endophytes are living inside plants without any harmful effects; the prospecting about them is increased day by day because they can produce bioactive compounds which can be used in different applications. Herein, the current study was aimed to isolate the endophytic fungi from the Ocimum basilicum plant as safe microorganisms and evaluate their biological activities. The results illustrated that three endophytic fungal strains were isolated and identified morphologically and genetically as Aspergillus nidulans, Aspergillus fumigatus, and Aspergillus flavus and deposited in gene bank under accession numbers MZ045561, MZ045562, and MZ045563 respectively. Moreover, cell-free filtrates of endophytic fungal strains were extracted using ethyl acetate, where these crude extracts exhibited promising antimicrobial activity against Staphylococcus aureus, Bacillus cereus, Bacillus subtilis, Escherichia coli, Salmonella typhimurium, Pseudomonas aeruginosa, Klebsiella pneumonia, and Candida albicans at a concentration of 1000 µg/mL. Furthermore, these endophytic strains exhibited a potential antioxidant activity where IC50 of the crude extract of A. nidulans, A. fumigatus, and A. flavus were (166.3, 68.4, and 347.1 µg/mL) and (151.2, 77.9, and 246.3 µg/mL) using DPPH and ABTS methods, respectively. Furthermore, the ethyl acetate crude extracts of these endophytic fungi did not exhibit any cytotoxic effect against Vero and Wi 38 normal cells. GC–MS analysis of the crude extract of A. nidulans, A. fumigatus, and A. flavus indicated the presence of 22, 22, and 20 active compounds, respectively. The major compounds in the fungal extracts are belonging to fatty acids, fatty acid esters, tetrahydrofurans, and sterols. In conclusion, the isolated endophytic A. nidulans, A. fumigatus, and A. flavus from Ocimum basilicum are promising sources for bioactive compounds.

The prevalence of opportunistic human fungal pathogens is increasing worldwide, and antimicrobial resistance is one of the greatest medical challenges the world faces. Therefore, this study aimed to develop a novel agent to control fungal pathogens. The honeybee products (honey, royal jelly, propolis, bee bread, and bee venom) were screened against unicellular fungal (UCF) pathogens (Cryptococcus neoformans, Kodamaea ohmeri, and Candida albicans) and the bee venom was only exhibited an inhibitory effect against them. The protein contents of crude bee venom were separated using the gel filtration technique into eight fractions which were visualized on sodium dodecyl sulfate–polyacrylamide gel electrophoresis (SDS–PAGE) to confirm the presence of five bands with molecular weights of 65, 43, 21, 15, and 3 KDa. Bee venom (BV) of Apis mellifera loaded chitosan nanoparticles were prepared by the ionotropic gelation method. The encapsulation efficiency%, average size, zeta potentials, and surface appearance by Transmission electron microscope (TEM) were evaluated for the prepared nanoparticles. The minimum inhibitory concentration (MIC) of crude BV and BV loaded chitosan nanoparticles (BV-CNPs) was evaluated against the offer mentioned UCF where the MIC values of crude BV were 6.25, 3.12 & 6.25 while MIC values in the case of BV-CNPs were decreased to 3.12, 3.12 & 1.56 mg/ml against C. neoformans, K. ohmeri and C. albicans, respectively. Also, the results showed that BV-CNPs suppressed the biofilm formation as well as yeast to hyphal transition formed by the examined UCF. These results revealed that BV-CNPs are a promising natural compound for fungal pathogens treatment. Graphical abstract

The herbal products proved to be more promising antimicrobials even though their antimicrobial activity is milder than commercially available antibiotics. Moreover, herbal drugs may act synergistically with antibiotics to kill microbes. In this study, we aimed to enhance the activity of penicillin against MRSA through combination with the active saponin fraction isolated from the Zygophyllum album plant. Three different types of metabolites (saponins, sterols, and phenolics) have been extracted from Zygophyllum album with ethanol and purified using different chromatographic techniques. The antibacterial activity of crude extract and the separated metabolites were checked against MRSA isolates, Saponin fraction (ZA-S) was only the active one followed by the crude extract. Therefore, the compounds in this fraction were identified using ultra-high-performance liquid chromatography connected to quadrupole time-of-flight mass spectrometry (UHPLC/QTOF-MS) operated in positive and negative ionization modes. UHPLC/QTOF-MS revealed the presence of major six ursane-type tritepenoidal saponins (Quinovic acid, Quinovic acid 3β-O-β-D-quinovopyranoside, Zygophylloside C, Zygophylloside G, Zygophylloside K and Ursolic acid), in addition to Oleanolic acid. Interaction studies between saponin fraction and penicillin against MRSA were performed through the checkerboard method and time-kill assay. According to checkerboard results, only three combinations showed a fractional inhibitory concentration index less than 0.5 at concentrations of (62.5 + 312.5, 62.5 + 156.25, and 62.5 + 78.125 of penicillin and ZA-S, respectively). Time kill assay results showed that the highest reduction in log10 colony-forming unit (CFU)/ml of initial inoculum of MRSA after 24 h occurred by 3.7 at concentrations of 62.5 + 312.5 (µg/µg)/ml of penicillin and ZA-S, respectively. Thus, the combination between saponin fraction of Zygophyllum album and penicillin with these concentrations could be a potential agent against MRSA that can serve as possible model for new antibacterial drug.

Regarding the crucial role of deubiquitinase (DUB) enzymes in many viruses, in particular, Adenovirus, HSV-1, coxsackievirus, and SARS-CoV-2, DUB inhibition was reported as an effective new approach to find new effective antiviral agents. In the present study, a new wave of 4-(2-nitrophenoxy)benzamide derivatives was designed and synthesized to fulfill the basic pharmacophoric features of DUB inhibitors. The molecular docking of the designed compounds against deubiquitinase enzymes of the aforementioned viruses was carried out. Significant molecular docking results directed us to conduct in vitro antiviral screening against the aforementioned viruses. The biological data showed very strong to strong antiviral activities with IC50 values ranging from 10.22 to 44.68 μM against Adenovirus, HSV-1, and coxsackievirus. Compounds 8c, 8d, 10b, and 8a were found to be the most potent against Adenovirus, HSV-1, coxsackievirus, and SAR-CoV-2, respectively. Also, the CC50 values of the examined compounds ranged from 72.93 to 120.50 μM. Finally, the in silico ADMET and toxicity studies demonstrated that the tested members have a good profile of drug-like properties. Furthermore, we concluded the structure–activity relationship (SAR) of the newly designed and synthesized compounds regarding their in vitro results, which may help medicinal chemists in further optimization to obtain more potential antiviral candidates in the near future as well.

Abdallah E Abdallah,1 Reda R Mabrouk,1 Mohamed R Elnagar,2 Amel Mostafa Farrag,3 Mohamed H Kalaba,4 Mohamed H Sharaf,4 Esmail M El-Fakharany,5 Dina Abed Bakhotmah,6 Eslam B Elkaeed,7 Maged Mohammed Saleh Al Ward1 1Pharmaceutical Medicinal Chemistry & Drug Design Department, Faculty of Pharmacy (Boys), Al-Azhar University, Cairo, 11884, Egypt; 2Department of Pharmacology and Toxicology, Faculty of Pharmacy, Al-Azhar University, Cairo, 11884, Egypt; 3Pharmaceutical Chemistry Department, Faculty of Pharmacy (Girls), Al-Azhar University, Cairo, Egypt; 4Botany and Microbiology Department, Faculty of Science, Al-Azhar University, Cairo, 11884, Egypt; 5Protein Research Department, Genetic Engineering and Biotechnology Research Institute, City of Scientific Research and Technological Applications, New Borg El Arab, Egypt; 6Chemistry Department, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia; 7Department of Pharmaceutical Sciences, College of Pharmacy, AlMaarefa University, Riyadh, 13713, Saudi ArabiaCorrespondence: Abdallah E Abdallah; Maged Mohammed Saleh Al Ward, Pharmaceutical Medicinal Chemistry & Drug Design Department, Faculty of Pharmacy (Boys), Al-Azhar University, Cairo, 11884, Egypt, Email Abdulla_emara@azhar.edu.eg; majed1000ward@hotmail.comBackground: Cancer is still a major world health threat, causing a high rate of mortality. VEGFR-2 inhibitor anticancer agents are of great significance. However, they showed some serious side effects.Purpose: To discover new effective and safer anticancer agents, a new series of piperazinylquinoxaline-based derivatives was designed and synthesized on the basis of the pharmacophoric features of VEGFR-2 inhibitor drugs.Methods: The new candidates were evaluated against A549 lung cancer cells, HepG-2 hepatoma cells, Caco-2 colon cancer cells, MDA breast cancer cells, and VEGFR-2 kinase. Moreover, cell cycle kinetics and apoptosis rates were studied in HepG-2 cells treated with compound 11, which was the most promising candidate.Results: The new derivatives revealed better antitumor results (IC50 from 6.48 to 38.58 μM) against the aforementioned cancer cell lines than sorafenib. Also, the new candidates showed VEGFR-2 inhibition with IC50 values ranging from 0.19 to 0.60 μM compared to 0.08 μM for sorafenib. Compound 11, meanwhile, showed IC50 values equal to 10.61, 9.52, 12.45, 11.52, and 0.19 μM against the cancer cell lines and VEGFR-2, respectively. Moreover, compound 11 raised the apoptosis rate in HepG-2 cells from 5% to 44% and caused 4, 2.3, and 3-fold increases in BAX/Bcl-2 ratio, caspase-3 level, and P53 expression, respectively, compared to control untreated cells. Finally, the new derivatives displayed the correct binding mode into VEGFR-2 kinase pocket, giving interactions with the essential residues.Conclusion: This work suggests that compound 11 is a very significant anticancer candidate, and piperazinylquinoxaline is an important scaffold in the development of new potential effective and safer VEGFR-2 inhibitor agents.Keywords: anticancer, apoptosis, molecular modeling, piperazinylquinoxaline, VEGFR-2 kinase, Western blot

Biological synthesis of nanoparticles is a promising approach that is comparatively inexpensive and eco-friendly. Among various microorganisms, actinobacteria have been found to be efficient in the synthesis of nanomaterials. In thisstudy, extracellular biosynthesis of silver nanoparticles (Ag-NPs) was investigated by mixing silver nitrate with culture filtrate of Streptomyces rochei strain MFA-37.The biosynthesized Ag-NPs were characterized by UV–Vis spectrophotometric analysis, and showed a peak of absorbance at 440 nm. Fourier transform infrared (FTIR) analysis showed amines and amides that are responsible for the stabilization of Ag-NPs. The morphology and size of nanoparticles were determined using high-resolution transmission electron microscopy, XRD and DLS techniques which indicated well dispersed, spherical Ag-NPs sized 2–20 nm, and the zeta potential of AgNPs reached -20.5 mV. Enhancement of antibacterial activity of fourteen antibiotics was conducted by combining antibiotics with synthesized AgNPs. The synergistic activities of AgNPs combination with antibiotics were determined using disc diffusion against two multi-drug resistant Staphylococcus aureus SA-185 and SA-325 recovered from Libya. The highest synergistic effects were 6.11 and 6.37 folds for Penicillin followed by 6.11 and 4.44 folds for Ciprofloxacin and 6.11 and 3.69 folds for Erythromycin for MRSA-185 and MRSA-325 , respectively. This activity of AgNPs and antibiotics could be valuable for the manufacture of hybrid drugs to kill or inhibit the MRSA infection especially in case of superficial injuries.

The small cracks in concrete constructions are inevitable due to deterioration during their service life throughout different load combination factors. In this study, we aimed to isolate, identify, and construct a bacterial consortium able to heal small cracks of concrete and enhance the different properties of concrete. Six isolates of bacillus, endospore-forming bacteria were isolated. There are only three isolates out of the six coded as NW-1, MK and NW-9 were showed the ability to produce urease enzyme and able to grow at 60°C with optimum growth at a temperature of 40°C. These isolates were survived in high pH, where isolate NW-1 was tolerated pH up to 11 with optimum growth at 10 while the isolates NW-9 and MK showed growth at pH 12 with an ideal growth at 10. CaCO3 production was observed by the three bacterial isolates whether in pure or mixed cultures (bacterial consortium) but the consortium consisting of MK and NW-9 was significantly the highest in productivity among them. Therefore, these two isolates were identified using 16s as Bacillus flexus MK-FYT-3 and Bacillus haynesii MK-NW-9 and deposited to GenBank under accession numbers MN965692 and MN965693 respectively. The effect of bacteria on some properties of concrete was studied, and the results showed that the compressive and tensile strengths of bio-concrete specimens were significantly increased by 31.29, 29 % after 7 days and 36.3, 39 % after 28 days of curing compared to control specimens. The results of permeability indicated that the bio-concrete specimens significantly showed less permeability than the control specimens by 21.1, 23.1% after 7 and 28 of curing, respectively. To determine the concrete density, Ultrasonic Pulse Velocity (UPV) test was performed, and the bio-concrete specimens gave higher values ​​than control specimens by 26 and 20% after curing for 7 and 28 days, respectively. Also, surface healing of concrete was observed visually, the bio-concrete showed white precipitates around and inside the cracks after 7 days, which led to almost complete sealing of concrete after 28 days of curing, while the control samples were showed only very slight deposits on the surface and away from the cracks. The micro-analysis of concrete samples using SEM and XRD were done. It was found that the bio-concrete specimens showed crystalline precipitate with different shapes under SEM, while no such deposits appeared in the control specimens. On the other hand, the XRD profile was explained the characteristic peaks of calcium carbonate in both the bio-concrete and the control specimens, but the peak intensity was higher in the bio-concrete than the control specimens. This reflects the effectiveness of bacterial consortium in repairing and preventing the concrete cracks from spreading in addition to improving the various properties of concrete leading to increasing its life and sustainability.

Athelia rolfsii TEMG (MH 236106) an exopolysaccharide (EPS) producing fungal strain was isolated and identified. Extraction, purification, characterization, antimicrobial, antioxidant, antiviral and antitumor activities of the polysaccharide were investigated. It characterized as a homopolysaccharide of glucose with a molecular weight of 345.622 kDa. The identification of the polysaccharide was conducted using scanning electron microscopy, energy dispersive X-ray analysis, 1H and 13C NMR spectra. The existence of β-1,3 and β-1,6 linkages suggests that EPS could be scleroglucan. The purified scleroglucan showed considerable antibacterial and antioxidant activities. The results indicated that, there was no cytotoxicity on normal cell (W138) and no effect on tumor cell lines including HepG2 and PC3 showing IC50 of 5096.83, 5885.80 and 4803.90 μg/mL, respectively. The results showed also that Sclg could reduce the cytopathic effect by 50% (EC50) at 15 and 50 μg/mL of herpes simplex virus type-1 (HSV-1) and influenza virus (H5N1), respectively.

Objective The aim of this study was to isolate and identify heavy metal-resistant and antibiotics-resistant bacteria from contaminated samples (wastewater and soil) collected from different industrial areas in Egypt and determine their role in heavy metal removing. Materials and methods Samples were collected from Helwan and 10th of Ramadan city areas and enriched in culture broth containing 200, 100, and 10 ppm of arsenic (As), lead (Pb), and cadmium (Cd) as AsHNa 2 O 4·H 2 O, Pb(NO 3 ) 2 , and CdSO 4 , respectively. The highly resistant isolate (ST6) was selected and identified biochemically and also subjected to 16S rDNA sequencing. The growth parameters were optimized and the maximum tolerable concentration of the respective metals as well as the antibiotic resistance was determined. Result and conclusion After enrichment culture we isolated and purified 20 bacterial isolates resistant to the respective heavy metals As, Pb, and Cd. The morphological, biochemical, and phylogenetical characteristics of the most resistant bacterial isolates (ST6) were studied. The results showed that this isolate belongs to the species Pseudomonas stutzeri. The optimum temperature was 35°C, whereas the optimum pH was in the range of 6-7. Maximum tolerable concentration values for As, Pb, and Cd were 3500, 1750, and 50 ppm, respectively. Also, the isolate ST6 showed resistance against different antibiotics. The metal removal ability was 42.5, 57.1, and 52.9% of As, Pb, and Cd, respectively. It was concluded that the ST6 isolate was resistant and removed high concentrations of As, Pb, and Cd. Hence, this isolate may play a role in bioremediation processes of heavy metal in polluted areas.