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Novel isoxazole–triazole conjugates have been efficiently synthesized using 3-formylchromone as starting material according to a multi-step synthetic approach. The structures of the target conjugates and intermediate products were characterized by standard spectroscopic techniques (1H NMR and 13C NMR) and confirmed by mass spectrometry (MS). The all-synthesized compounds were screened for their antibacterial activity against three ATCC reference strains, namely Staphylococcus aureus ATCC 25923, Staphylococcus aureus ATCC BAA-44, and Escherichia coli ATCC 25922 as well as one strain isolated from the hospital environment Pseudomonas aeruginosa. The findings indicate that conjugate 7b exhibits a stronger antibacterial response against the tested Escherichia coli ATCC 25922 and Pseudomonas aeruginosa pathogenic strains compared to the standard antibiotics. Furthermore, hybrid compound 7b proved to have a bactericidal action on the Escherichia coli ATCC 25922 strain, as evidenced by the results of the MBC determination. Moreover, the ADMET pharmacokinetic characteristics revealed a favorable profile for the examined compound, as well as a good level of oral bioavailability. Molecular docking and molecular dynamics simulations were performed to explore the inhibition mechanism and binding energies of conjugate 7b with the proteins of Escherichia coli and Pseudomonas aeruginosa bacterial strains. The in silico results corroborated the data observed in the in vitro evaluation for compound 7b.

Diabetes is a global health concern with significant implications for individuals and healthcare systems. Finding effective and safe antidiabetic agents is crucial for the management of this chronic disease. Natural products have emerged as potential alternatives to allopathic drugs, offering a vast source of bioactive compounds. In this study, we conducted an assessment of the antidiabetic potential of Origanum compactum essential oil, employing a two-pronged approach, i.e., experimental investigation and computational docking analysis. The results of gas chromatography–mass spectrometry (GC-MS) showed that thymol (54.6%), carvacrol (23.18%), and p-cymene (7.12%) were the major compounds. Experimental assessments revealed higher IC50 values (150 µg/mL for α-amylase; 120 µg/mL for α-glucosidase) of O. compactum oil, compared to the control drug acarbose. In silico analysis revealed the best binding affinity of the oil components (carvacrol and thymol) with human NADPH oxidase, while the lysosomal acid-α-glucosidase and salivary amylase also demonstrated good binding affinity towards carvacrol and thymol. Our findings highlight the translational potential of O. compactum oil-based treatment for diabetes mellitus and provide a basis for further studies on the modulation of NADPH oxidase, amylase inhibition, and α-glucosidase by antidiabetic natural products. However, further in vivo investigations are strongly required to confirm the results of in vitro antidiabetic effect of O. compactum EO.

Overexpression of polo-like kinase 1 (PLK1) has been found in many different types of cancers. With its essential role in cell proliferation, PLK1 has been determined to be a broad-spectrum anti-cancer target. In this study, 3D-QSAR, molecular docking, and molecular dynamics (MD) simulations were applied on a series of novel pteridinone derivatives as PLK1 inhibitors to discover anti-cancer drug candidates. In this work, three models—CoMFA (Q² = 0.67, R² = 0.992), CoMSIA/SHE (Q² = 0.69, R² = 0.974), and CoMSIA/SEAH (Q² = 0.66, R² = 0.975)—of pteridinone derivatives were established. The three models that were established gave Rpred2 = 0.683, Rpred 2= 0.758, and Rpred 2= 0.767, respectively. Thus, the predictive abilities of the three proposed models were successfully evaluated. The relations between the different champs and activities were well-demonstrated by the contour chart of the CoMFA and CoMSIA/SEAH models. The results of molecular docking indicated that residues R136, R57, Y133, L69, L82, and Y139 were the active sites of the PLK1 protein (PDB code: 2RKU), in which the more active ligands can inhibit the enzyme of PLK1. The results of the molecular dynamic MD simulation diagram were obtained to reinforce the previous molecular docking results, which showed that both inhibitors remained stable in the active sites of the PLK1 protein (PDB code: 2RKU) for 50 ns. Finally, a check of the ADME-Tox properties of the two most active molecules showed that molecular N° 28 could represent a good drug candidate for the therapy of prostate cancer diseases.

Forty-four bicyclo ((aryl) methyl) benzamides, acting as glycine transporter type 1 (GlyT1) inhibitors, are developed using molecular modeling techniques. QSAR models generated by multiple linear and non-linear regressions affirm that the biological inhibitory activity against the schizophrenia disease is strongly and significantly correlated with physicochemical, geometrical and topological descriptors, in particular: Hydrogen bond donor, polarizability, surface tension, stretch and torsion energies and topological diameter. According to in silico ADMET properties, the most active ligands (L6, L9, L30, L31 and L37) are the molecules having the highest probability of penetrating the central nervous system (CNS), but the molecule 32 has the highest probability of being absorbed by the gastrointestinal tract. Molecular docking results indicate that Tyr124, Phe43, Phe325, Asp46, Phe319 and Val120 amino acids are the active sites of the dopamine transporter (DAT) membrane protein, in which the most active ligands can inhibit the glycine transporter type 1 (GlyT1). The results of molecular dynamics (MD) simulation revealed that all five inhibitors remained stable in the active sites of the DAT protein during 100 ns, demonstrating their promising role as candidate drugs for the treatment of schizophrenia.

Vinegar is a natural product widely used in food and traditional medicine thanks to its physicochemical properties and its richness in bioactive molecules. However, its direct use by consumers can have complications and undesirable effects. Therefore, this study contributes to investigating the physicochemical and biological properties of eleven vinegars marketed in Morocco. Determination of pH, acetic acid, conductivity, total soluble solids and alcohol content in vinegar was carried out. The polyphenols (TP), flavonoids (TF), and condensed tannins (CT) content was determined, and their antioxidant activities were evaluated using 2,2-diphenyl-1-picryl Hydrazyl (DPPH), Ferric Reducing Antioxidant Power (FRAP) and Phosphomolybdenum Reduction Assay (TAC). Then, the antimicrobial activity was studied against four pathogenic bacteria and two fungal strains, using the disk diffusion and the microdilution method. This study showed a wide range of acetic acid values from 0.65 ± 0.29 to 5.15 ± 0.20%. The high value of TP, TF, and CT in our samples V10, V9, and V4 was 655.00 ± 22.2 µgGAE/mL, 244.53 ± 11.32 µgQE/mL and 84.63 ± 1.00 µgTAE/mL, respectively. The tested strains showed variable sensitivities to the different samples with inhibition zones ranging from 6.33 ± 2.08 to 34.33 ± 0.58 mm. The lowest minimum inhibition concentrations were recorded against Staphylococcus aureus ATCC29213 ranging from 1.95 to 7.81 µL/mL. While Aspergillus niger ATCC16404 showed resistance against all of the analyzed samples. In general, vinegar commercialized in Morocco presents a variable range of products with variable properties. Indeed, must take into account this diversity when using it. A future study is needed to identify the phytochemical composition that will further the comprehension of this variability and contribute to its valorization.