Silver Phosphate, Ag₃PO₄, being a highly capable clinical molecule, an ultrasonic method was employed to synthesize the M-Ag₃PO_4, (M = Se, Ag, Ta) nanoparticles which were evaluated for antibacterial and cytotoxicity activities post-characterization. Escherichia coli and Staphylococcus aureus were used for antibacterial testing and the effects of sonication on bacterial growth with sub-MIC values of M-Ag₃PO₄ nanoparticles were examined. The effect of M-Ag₃PO₄ nanoparticles on human colorectal carcinoma cells (HCT-116) and human cervical carcinoma cells (HeLa cells) was examined by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide) assay and DAPI (4′,6-diamidino-2-phenylindole) staining. Additionally, we analyzed the effect of nanoparticles on normal and non-cancerous human embryonic kidney cells (HEK-293). Ag-Ag₃PO₄ exhibited enhanced antibacterial activity followed by Ta-Ag₃PO_4, Ag₃PO₄, and Se-Ag₃PO₄ nanoparticles against E. coli. Whereas the order of antibacterial activity against Staphylococcus aureus was Ag₃PO₄ > Ag-Ag₃PO₄ > Ta-Ag₃PO₄ > Se-Ag₃PO₄, respectively. Percentage inhibition of E. coli was 98.27, 74.38, 100, and 94.2%, while percentage inhibition of S. aureus was 25.53, 80.28, 99.36, and 20.22% after treatment with Ag₃PO₄, Se-Ag₃PO₄, Ag-Ag₃PO₄, and Ta-Ag₃PO_4, respectively. The MTT assay shows a significant decline in the cell viability after treating with M-Ag₃PO₄ nanoparticles. The IC₅₀ values for Ag₃PO_4, Se-Ag₃PO_4, Ag-Ag₃PO₄, and Ta-Ag₃PO₄ on HCT-116 were 39.44, 28.33, 60.24, 58.34 µg/mL; whereas for HeLa cells, they were 65.25, 61.27, 75.52, 72.82 µg/mL, respectively. M-Ag₃PO₄ nanoparticles did not inhibit HEK-293 cells. Apoptotic assay revealed that the numbers of DAPI stained cells were significantly lower in the M-Ag₃PO₄-treated cells versus control.

Novel semisynthetic coumarin derivatives were synthesized to be developed as chemotherapeutic anticancer agents through topoisomerase II, VEGFR2 inhibition that leads to apoptotic cancer cell death. The coumarin amino acids and dipeptides derivatives were prepared by the reaction of coumarin-3-carboxylic acid with amino acid methyl esters following the N,N-dicyclohexylcarbodiimide (DCC) method and 1-hydroxy-benzotriazole (HOBt), as coupling reagents. The synthesized compounds were screened towards VEGFR2, and topoisomerase IIα proteins to highlight their binding affinities and virtual mechanism of binding. Interestingly, compounds 4k (Tyr) and 6c (β-Ala-L-Met) shared the activity towards the three proteins by forming the same interactions with the key amino acids, such as the co-crystallized ligands. Both compounds 4k and 6c exhibited potent cytotoxic activities against MCF-7 cells with IC₅₀ values of 4.98 and 5.85 µM, respectively causing cell death by 97.82 and 97.35%, respectively. Validating the molecular docking studies, both compounds demonstrated promising VEGFR-2 inhibition with IC₅₀ values of 23.6 and 34.2 µM, compared to Sorafenib (30 µM) and topoisomerase-II inhibition with IC₅₀ values of 4.1 and 8.6 µM compared to Doxorubicin (9.65 µM). Hence, these two promising compounds could be further tested as effective and selective target-oriented active agents against cancer.

Background/Objectives: Glucagon-like peptide-1 (GLP-1) receptor is currently one of the most explored targets exploited for the management of diabetes and obesity, with many aspects of its mechanisms behind cardiovascular protection yet to be fully elucidated. Research dedicated towards the development of oral GLP-1 therapy and non-peptide ligands with broader clinical applications is crucial towards unveiling the full therapeutic capacity of this potent class of medicines. Methods: This study describes the virtual screening of a natural product database consisting of 695,133 compounds for positive GLP-1 allosteric modulation. The database, obtained from the Coconut website, was filtered according to a set of physicochemical descriptors, then was shape screened against the crystal ligand conformation. This filtered database consisting of 26,325 compounds was used for virtual screening against the GLP-1 allosteric site. Results: The results identified ten best hits with the XP score ranging from −9.6 to −7.6 and MM-GBSA scores ranging from −50.8 to −32.4 and another 58 hits from docked pose filter and a second round of XP docking and MM-GBSA calculation followed by molecular dynamics. The analysis of results identified hits from various natural products (NPs) classes, to whom attributed antidiabetic and anti-obesity effects have been previously reported. The results also pointed to β-lactam antibiotics that may be evaluated in drug repurposing studies for off-target effects. The calculated ADMET properties for those hits revealed suitable profiles for further development in terms of bioavailability and toxicity. Conclusions: The current study identified several NPs as potential GLP-1 positive allosteric modulators and revealed common structural scaffolds including peptidomimetics, lactams, coumarins, and sulfonamides with peptidomimetics being the most prominent especially in indole and coumarin cores.

Glucagon like peptide-1 (GLP-1) receptor is currently one of the most explored targets exploited for the management of diabetes and obesity, with many aspects of its mechanisms behind cardiovascular protection yet to be fully elucidated. Currently available therapy is limited to parenteral GLP-1 agonists with the demand for orally compatible formulations growing. Research dedicated towards the development of oral GLP-1 therapy and non-peptide ligands with broader clinical applications is crucial towards unveiling the full therapeutic capacity of this potent class of medicines. This study describes the virtual screening of a natural product database consisting of 695,133 compounds for positive GLP-1 allosteric modulation. The database, obtained from the Coconut website was filtered according to a set of physicochemical descriptors, and the quantitative estimation of drug likeness (QED) index. The resulting database which consisted of 158,523 compounds, was shape screened against the crystal ligand conformation and was filtered using a shape similarity (SS) score threshold of 0.3. This resulted in a final database of 26,325 compounds that was used for virtual screening against the GLP-1 allosteric site using three docking stages including high throughput virtual screening (HTVS), standard precision (SP), and extra precision (XP) docking. The results identified ten best hits with XP score ranging from -9.6 to -7.6 and MM-GBSA scores ranging from -50.8 to -32.4. The initial SP and XP shortlists were further subjected to docking pose filtration according to a set of criteria based on the crystal structure binding requirements. The resulting 58 hits were redocked using XP docking and their MM-GBSA were calculated and were found to be in the range of -7.4 to -3.7 and -52.77 to -13.02 for XP scores and MM-GBSA respectively. Molecular dynamics was performed on selected hits to verify binding stability within the GLP-1 allosteric binding pocket. The analysis of results identified hits from various natural products (NP) classes notably Sesquiterpenoids, Coumarins, and Phenylpropanoids, to whom attributed antidiabetic and anti-obesity effects have been previously reported. The results also pointed to unexpected compounds including β-lactam antibiotics including Valclavam, Cyclothiocurvularin B, Azidocillin, Ampicillin, Metampicillin, and Timocillin that may be evaluated in drug repurposing studies for off-target effects. The calculated ADMET properties for those hits revealed suitable profiles for further development in terms of bioavailability and toxicity. The structure analysis of the 68 hits revealed common structural scaffolds including peptidomimetics, lactams, coumarins, and sulfonamides with peptidomimetics being the most prominent especially in indole and coumarin cores.

The olive leaf extract and olive leaf indicated a high potential for application in food additives and foodstuffs. It could be these bio-products useful and important in condition therapy related with oxidative stress and can use it to develop functional foods and to improve the food's shelf life. The olive leaf chemical composition of Oleaeuropaea L. grown from eljouf in Saudi Arabia, using solvents of increasing polarity cyclohexane, dichloromethane, chloroform, ethyl acetate, methanol and ethanol was determined using by GC/MS. Furthermore, the antioxidant activity (diphenylpicrylhydrazyl (DPPH), anti-aging, and anti-tuberculosis of olive leaf extracts were evaluated. The results indicated that extract of Oleaeuropaea L. has a considerable contains in polyphenols (hydroxytyrosol, oleuropein and their derivatives) regarding its antioxidant effects, the major components were detected by GC/MS in Olea dichloromethane extract are Hexadecanoic acid (15.82%), 7(4Dimethylaminophenyl)3,3,12trimethyl3,12dihydro6 Hpyrano[2,3c]acridin 6 one (11.21%), and in Olea chloroform extract are Hexatriacontane (12.68%), nTetratr iacontane (10.95%). The results concluded that the plant extract of chloroform showed no anti-aging activities and the lower anti-aging activities for cyclohexane extract, while, the Olea dichloromethane extract was the most active extract. The obtained data confirmed that the most active extract of anti-tubercolisis was for chloroform and ethyl acetate extract, while, anti-tubercolisis activity of ethanolic extract was the lower. The extract amount as well as the solvent polarity influence the inhibitory activity. A favorable connection was demonstrated inter alia the leaf extracts antioxidant activity and the content of total phenol.