Pharmacokinetic and molecular docking studies to pyrimidine drug using Mn3O4 nanoparticles to explore potential anti-Alzheimer activity.

Alzheimer disease (AD) is the cause of dementia and accounts for 60-80% cases. Tumor Necrosis Factor-alpha (TNF-α) is a multifunctional cytokine that provides resistance to infections, inflammation, and cancer. It developed as a prospective therapeutic target against multiple autoimmune and inflammatory disorders. Cholinergic insufficiency is linked to Alzheimer's disease, and several cholinesterase inhibitors have been created to treat it, including naturally produced inhibitors, synthetic analogs, and hybrids. In the current study, we tried to prepared compounds may also support the discovery and development of novel therapeutic and preventative drugs for Alzheimer's using manganese tetroxide nanoparticles (Mn3O4-NPs) as a catalyst to generate compounds with excellent reaction conditions. The Biginelli synthesis yields 4-(4-cyanophenyl)-6-oxo-2-thioxohexahydropyrimidine-5-carbonitrile when the 4-cyanobenzaldehyde, ethyl cyanoacetate, and thiourea were coupled with Mn3O4-NPs to produce compound 1. This multi-component method is non-toxic, safe, and environmentally friendly. The new approach reduced the amount of chemicals used and preserved time. Compound 1 underwent reactions with methyl iodide, acrylonitrile, chloroacetone, ethyl chloroacetate, and chloroacetic acid/benzaldehyde, each of the synthetized compounds was docked with TNF-α converting enzyme. These compounds may also support the discovery and development of novel therapeutic and preventative drugs for Alzheimer's disease. The majority of the produced compounds demonstrated pharmacokinetic features, making them potentially attractive therapeutic candidates for Alzheimer's disease treatment.

Synthesis, structural, molecular docking, and in vitro biological activities of Cu-doped ZnO nanomaterials.

Copper-doped ZnO nanoparticles with the formula Zn1-x(Cu)O, where x = 0.0, 0.03, 0.05, and 0.07 were produced using the co-precipitation process. Physical, chemical, and structural properties were properly examined. Powdered X-ray diffraction (P-XRD) patterns revealed the formation of hexagonal wurtzite crystal structure in all samples, through atomic substitutional incorporation in the Cu-doped ZnO lattice. The presence of Cu ions and their dissolution in the host ZnO crystal structure was supported by FT-IR spectra. HR-TEM images were used to assess the average size, morphology, and shape regularity of the synthesized samples. The form and homogeneity of the ZnO changed when Cu ions were substituted, as evidenced by FE-SEM/EDX analysis. The presence of copper signals in the Cu-doped samples indicates that the doping was successful. The decrease in zeta potential with an increased copper doping percentage designates that the nanoparticles (NPs) are more stable, which could be attributed to an increase in the ionic strength of the aqueous solution. The synthesized NPs were evaluated for their substantial in vitro antioxidant properties. In addition, the antimicrobial efficacy of the materials was tested against pathogenic microorganisms. Regarding the anti-diabetic activity, the 7Cu ZnO sample showed the highest inhibitory effect on the α-amylase enzyme. No variations were observed in the activities of the acetylcholinesterase enzyme (AChE) and proteinase enzymes with ZnO and samples doped with different concentrations of Cu. Therefore, further studies are recommended to reveal the in-vitro anti-diabetic activity of the studied doped samples. Finally, molecular docking provided valuable insights into the potential binding interactions of Cu-doped ZnO with α-amylase, FabH of E. coli, and Penicillin-binding proteins of S. aureus. These outcomes suggest that the prepared materials may have an inhibitory effect on enzymes and hold promise in the battle against microbial infections and diabetes.

Doxorubicin loaded cerium substituted hydroxyapatite nanoparticles: A promising new therapeutic approach for bone regeneration, doxorubicin delivery, and cancer treatment.

The current study used the precipitation method to prepare pure calcium hydroxyapatite (HA) and cerium-substituted hydroxyapatite (Ce-HA) nanoparticles, where cerium ions were exchanged into the HA structure at different concentrations ranging from 3 to 7 wt%. X-ray powder diffraction (XRD), field emission scanning electron microscopy (FE-SEM), high resolution transmission electron microscopy (HR-TEM), Fourier transform infrared (FTIR) spectroscopy, Brunauer-Emmett-Teller (BET) surface area measurements, and zeta potential were used to examine the structural characteristics of the nanoparticles. Additionally, the antibacterial and antifungal effects of the produced materials on Gram-positive, Gram-negative, and fungal bacterial species were studied. Nanoparticles with cerium doping showed effective antibacterial and antifungal properties. All samples were tested for bioactivity in simulated body fluid (SBF), and the formation of an apatite layer on their surfaces was highlighted using SEM in conjunction with energy-dispersive X-rays (EDX).Doxorubicin (DOX) release from Ce-HA nanoparticles and pure HA was tested in phosphate-buffered saline (PBS) for up to 28 days. Both nanoparticles were able to release the drug while still being semi-fully loaded. Similarly, the cytotoxic effect of all produced samples on the MG-63 cell line was evaluated, and all samples showed good cytocompatibility. The cytotoxic effect of doxorubicin-loaded nanoparticles showed promising anticancer activity against bone cancer cells, especially samples with high cerium content. The resulting nanoparticles show excellent promising ability for the delivery of doxorubicin to bone cancer with the capacity for bone regeneration.

CuO nanoparticles for green synthesis of significant anti-Helicobacter pylori compounds with in silico studies.

Helicobacter pylori (H. pylori) is a universal health intimidation as mentioned by the World Health Organization. The primary causal agent linked to a number of illnesses, including inflammation and the development of stomach ulcers, is Helicobacter pylori. Since, H. pylori develops antibiotic resistance quickly, current H. pylori treatment approaches are becoming less effective. Our research aims to highlight novel formulation antibiotics using CuO-NPs as catalysts and studied their activity as anti-helicobacter pylori supported by computational studies (POM analysis and molecular docking) software. They were designed for anti-Helicobacter Pylori action. All compounds revealed a bactericidal effect better than the reference McFarland standards.

A comparative study on the antifungal effect of potassium sorbate, chitosan, and nano-chitosan against Rhodotorula mucilaginosa and Candida albicans in skim milk acid-coagulated (Karish) cheese.

Background and Aim: Yeasts are common contaminants in the cheese industry, which frequently arise from raw milk, the surrounding environment, and equipment, resulting in economic losses in addition to health hazards. This study aimed to compare the antifungal effect of chitosan and nano-chitosan as natural preservatives with a commonly used chemical preservative (potassium sorbate) against Rhodotorula mucilaginosa and Candida albicans. Materials and Methods: Laboratory Karish cheese was manufactured with the addition of potassium sorbate, chitosan, nano-chitosan, and their combinations at different concentrations. The survival of R. mucilaginosa and C. albicans was monitored in different treatments (CR, PR1, PR2, CR1, CR2, NR1, NR2, MR, CC, PC1, PC2, CC1, CC2, NC1, NC2, MC) during storage in a refrigerator with continuous measurement of pH. The impact of using these antifungal agents on the organoleptic parameters of Karish cheese during storage was also evaluated. Results: There was a significant decrease in the count of yeasts in all treatments from the 3rd day of storage, while the mixture of 0.1% potassium sorbate (MR) and 2% chitosan (MC) improved the antifungal effect of chitosan with a lower potassium sorbate concentration and showed the best antifungal effects against both R. mucilaginosa and C. albicans. This combination reduced the yeast count from 8.92 and 9.57 log10 colony-forming unit (CFU)/g in MR and MC treatments, respectively, until it became undetectable on the 9th day of storage, which was earlier than for all other treatments. It was noted that the addition of chitosan nanoparticles (ChNPs) at either 0.25% (NR1 and NC1) or 0.5% (NR2 and NC2) during the manufacturing of Karish cheese significantly lowered the counts of R. mucilaginosa and C. albicans compared with chitosan with a higher molecular weight, but significantly lower than potassium sorbate until 6th day of storage as all treatments of chitosan nanoparticles became significantly higher than potassium sorbate treatments. After 9 days of storage, NR2 and NC2 treatments showed the most significant decreases in count (3.78 and 4.93 log10 CFU/g, respectively), indicating better stability of ChNPs. At the end of the storage period, PR2, PC2, CR2, and CC2 showed significantly high pH values among the groups of 4.8, 5.0, 4.8, and 5.1, respectively. The overall acceptability was significantly higher in treated Karish cheese samples than in the control group, especially at the end of the storage period. Conclusion: Potassium sorbate, chitosan, and ChNPs are effective antifungal preservatives against R. mucilaginosa and C. albicans. In addition, the combination of chitosan with potassium sorbate showed synergistic antifungal activity. These additives also preserve the sensorial criteria longer than for cheese without preservatives.

Formulation and evaluation of alginate-gelatin hydrogel scaffolds loaded with zinc-doped hydroxyapatite and 5-fluorouracil.

Alginate and gelatin are natural macromolecules used to formulate biocompatible drug delivery systems. Hydroxyapatite (HA) is an osteophilic ceramic used to prepare bone scaffolds. The current study aimed at preparing and characterizing HA, zinc-doped HA, and 5-fluorouracil(5-FU)-loaded alginate-gelatin-based hydrogel scaffolds using different crosslinking solutions. 5-FU incorporation efficiency, in-vitro drug release, antitumor bioassays, FTIR, X-ray-diffraction (XRD), High-Resolution Transmission, and Scanning-Electron Microscope (HR-TEM and SEM) studies were conducted. XRD showed the incorporation of Zn2+ into HA structure with a deformity in HA crystal lattice and inhibited crystal growth. FTIR-spectra represented the characteristic bands corresponding to HA structure. HR-TEM showed a decreased HA crystal size and rod-like crystallites that increased with increasing zinc content. Zn2+ content and 5-FU-loading caused significant effects on the scaffolds' thickness (p-value = 0.021 and 0.035, respectively). Burst 5-FU release within 10-15 min followed by 100 % release within 4 h was observed. Zinc content showed a significant positive effect on the cytotoxicity% of the blank and drug-loaded scaffolds. XRD and FTIR studies revealed that 5-FU was completely incorporated into the hydrogel with no chemical interaction. SEM-imaging showed interconnected pores and needle-shaped drug particles. The prepared formulations showed promising physico-chemical properties for targeted delivery of 5-FU in the form of biocompatible bone scaffolds.

TiO2 nanoparticle as catalyst for an efficient green one-pot synthesis of 1H-3-Indolyl Derivatives as significant antiviral activity.

Titanium dioxide nanoparticles (TiO2- NPs) are produced in large quantities for an extensive range of applications. They retain variable physicochemical properties, which influence their bioactivity. The condensation synthesis of 3-acetylindol, thiophene-2-carbaldehyde and malononitrile in the existence of TiO2 nanoparticle yields 2-amino-6-(1H-indol-3-yl)-4-(thiophen-2-yl)-4H-pyran-3-carbonitrile derivatives. The yielded compound 2 reacted with (formic acid, formamide, ethyl chloroacetate, chloroacetyl chloride, thiourea and sodium nitrite). This three-combination system is safe, ecologically friendly, and non-toxic. The proposed system helped in time preservation and reduction in chemical consumption. The synthesized compounds were screened for antiviral activity against Vero cells (HAV). Antiviral impact percent for samples 2, 5, 6 and 7 versus HAV were 81.98, 91.05, 9.21, and 21.95%, respectively. The viral efficacy of Sample 5 was the strongest against HAV.