A series of new heterocycle hybrids incorporating pyrazole and isoxazoline rings was successfully synthesized, characterized, and evaluated for their antimicrobial responses. The synthesized compounds were obtained utilizing N-alkylation and 1,3-dipolar cycloaddition reactions, as well as their structures were established through spectroscopic methods and confirmed by mass spectrometry. To get more light on the regioselective synthesis of new hybrid compounds, mechanistic studies were performed using DFT calculations with B3LYP/6-31G(d,p) basis set. Additionally, the results of the preliminary screening indicate that some of the examined hybrids showed potent antimicrobial activity, compared to standard drugs. The results confirm that the antimicrobial activity is strongly dependent on the nature of the substituents linked pyrazole and isoxazoline rings. Furthermore, molecular docking studies were conducted to highlight the interaction modes between the investigated hybrid compounds and the Escherichia coli and Candida albicans receptors. Notably, the results demonstrate that the investigated compounds have strong protein binding affinities. The stability of the formed complexes by the binding between the hybrid compound 6c, and the target proteins was also confirmed using a 100 ns molecular dynamics simulation. Finally, the prediction of ADMET properties suggests that almost all hybrid compounds possess good pharmacokinetic profiles and no signs of observed toxicity, except for compounds 6e, 6f, and 6g.

In this work, we report the synthesis of some new pyrazole derivatives via an efficient and practical procedure. The structures of the obtained compounds were established using different spectroscopic techniques such as NMR and FT-IR spectroscopy as well as high resolution mass spectrometry (HRMS). The synthesized compounds were screened for their antimicrobial activity against the following pathogenic microorganisms: Listeria innocua (CECT 4030), Staphylococcus aureus (CECT 976), Escherichia coli (K12), and Candida albicans (ATCC 10231). The results of the in vitro tests reveal that compounds 5c, 9b, and 9c exhibit important antimicrobial activity against some tested microbe strains, and show excellent bactericidal and fungicidal activities. A molecular docking study was performed on the most active compounds against E. coli and C. albicans receptors, in order to determine the modes of hydrogen bonding, and electrostatic and hydrophobic interactions that occur between the selected ligands and the target proteins. Furthermore, the 3D-QSAR study based on CoMFA and CoMSIA analyses ascertained a good correlation between the antibacterial activity of the pyrazole derivatives and their structural parameters. The structural features identified in these analyses were successfully used to design new pyrazole derivatives that show better in silico antimicrobial activity than the synthesized ones. In addition, most of the synthesized and the newly designed compounds show good drug-like properties. The ADME-Tox profiles indicate a good oral bioavailability. The newly designed compounds were subjected to molecular docking, which showed that they could form stable complexes with the E. coli receptor. Therefore, the obtained results in this study might provide important information for designing and synthesizing new pyrazoles with enhanced antimicrobial activity.

This work describes the synthesis, characterization, and in vitro and in silico evaluation of the biological activity of new functionalized isoxazole derivatives. The structures of all new compounds were analyzed by IR and NMR spectroscopy. The structures of 4c and 4f were further confirmed by single crystal X-ray and their compositions unambiguously determined by mass spectrometry (MS). The antibacterial effect of the isoxazoles was assessed in vitro against Escherichia coli, Bacillus subtilis, and Staphylococcusaureus bacterial strains. Isoxazole 4a showed significant activity against E. coli and B. subtilis compared to the reference antibiotic drugs while 4d and 4f also exhibited some antibacterial effects. The molecular docking results indicate that the synthesized compounds exhibit strong interactions with the target proteins. Specifically, 4a displayed a better affinity for E. coli, S. aureus, and B. subtilis in comparison to the reference drugs. The molecular dynamics simulations performed on 4a strongly support the stability of the ligand–receptor complex when interacting with the active sites of proteins from E. coli, S. aureus, and B. subtilis. Lastly, the results of the Absorption, Distribution, Metabolism, Excretion and Toxicity Analysis (ADME-Tox) reveal that the molecules have promising pharmacokinetic properties, suggesting favorable druglike properties and potential therapeutic agents.

Artemisia annua (AA) is an aromatic plant belonging to the Asteraceae family, which has long been known for its several medicinal virtues. In addition, essential oils (EOs) extracted from AA have a wide range of therapeutic properties. Therefore, this study aimed to investigate the phytochemical composition, anti-microbial, and anti-oxidant properties of Artemisia annua essential oil (EOAA). EO was extracted, and its chemical constituents were ascertained by the use of GC-MS analysis. EOAA shows remarkable antioxidant capacities of DPPH free radical scavenging with an IC₅₀ value of 29 ± 5.3 μg/mL and ferric reducing antioxidant power with an EC₅₀ value of 9.21 ± 0.3 µg/mL, and it also has a good total antioxidant capacity of 911.59 ± 115.71 milligrams of ascorbic acid equivalence per gram of EO (mg AAE/g EO). Moreover, the in vitro antimicrobial screening results indicate that EOAA has shown promising antibacterial activity, especially against the Escherichia coli strain, and it also shows significant antifungal activity against Fusarium oxysporum and Candida albicans yeasts. Taken together, our findings highlight the importance of EOAA as a source of strong antioxidant and antimicrobial agents, which could be used as an alternative form to control free radicals and combat drug-resistant microbes.