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.

This review investigates the convergence of nanotechnology and essential oils in advanced dermocosmetic delivery. It outlines the pivotal role of inorganic and polymeric nanoparticles, such as titanium dioxide, zinc oxide, and gold nanocarriers, in cosmeceutical applications, facilitating slow release, deeper skin penetration, and increased retention of active compounds. Essential oils, renowned for therapeutic benefits, face translation challenges due to volatility and low water solubility. This review explores the potential use of plant nanovesicles as carriers, emphasizing safety, stability, and scalability, offering a sustainable and cost-effective industrial application. Nanomaterial integration in consumer products, particularly cosmetics, is prevalent, with nanocarriers enhancing the permeation of bioactive compounds into deeper skin layers. The review emphasizes recent nanotechnological advancements, covering nanoparticle penetration, experimental models, and therapeutic applications in dermatology, ranging from non-invasive vaccination to transdermal drug delivery. Additionally, the review delves into nanomaterials’ role in addressing skin aging, focusing on tissue regeneration. Nanomaterials loaded with cosmeceuticals, such as phytochemicals and vitamins, are explored as promising solutions to mitigate signs of aging, including wrinkles and dry skin, providing innovative approaches to skin rejuvenation. Overall, the review offers a comprehensive synthesis of essential oil–nanoparticle synergy, shedding light on the current landscape and future potential of advanced dermocosmetic delivery systems.

Antimicrobial resistance (AMR) has severely compromised the clinical utility of classical sulfonamide antibiotics, primarily owing to the emergence of resistance‐associated dihydropteroate synthase variants. In this study, sixteen N‐(1H‐indazolyl) aryl sulfonamide hybrids were evaluated as potential DHPS inhibitors against Escherichia coli and Staphylococcus aureus using disk diffusion, broth microdilution (MIC ₈₀ ), and minimum bactericidal concentration (MBC) assays. Active compounds were characterized by in silico ADME and toxicity profiling, with molecular docking performed against wild‐type DHPS and the sulfonamide‐resistant Sul1 variant. Antibacterial activity was species‐dependent: compound 4 showed the strongest activity against E. coli (MIC = 32 µg/mL), while compounds 11 and 16 were most potent against S. aureus (MIC = 32 µg/mL), outperforming sulfathiazole and sulfisoxazole. All hybrids showed superior docking affinities to sulfamethoxazole (SMX), with compound 11 showing the highest affinity for wild‐type DHPS (−7.79 kcal/mol); compound 4 retained favorable binding against Sul1 (−6.83 kcal/mol), suggesting potential resistance resilience. Structure–activity analysis showed antibacterial efficacy is governed by aryl sulfonyl electronic effects, steric balance at the C7 indazole position, and physicochemical properties affecting Gram‐negative membrane permeability. These findings support indazole–sulfonamide hybrids as promising scaffolds that may retain predicted binding complementarity toward the Sul1‐resistant DHPS variant, warranting validation against resistant isolates and purified DHPS enzymes.

Two regioisomers obtained from the same reaction and differing in the position of an n-butyl substituent, i.e. on either an imidazoyl-N ( 2 ) or a pyridyl-N ( 3 ), have been characterised. Different electronic structures are evident, especially in key bond lengths and angles in the imidazoyl and pyridyl rings, as discerned by X-ray crystallography, and by geometry-optimisation, natural bonding orbital and electrostatic potential charge calculations. The distinctive molecular packing in their crystals has been confirmed by Hirshfeld surface analysis as well as by interaction energy and energy framework calculations. These differences notwithstanding, the calculated lattice energies indicate very similar stabilisation between the molecules in their crystals, i.e. −101.3 and −103.5 kJ/mol for 2 and 3 , respectively, consistent with their similar calculated molecular volumes (376.8 cf. 374.1 Å ³ ), packing coefficients (69.0 cf. 69.5 %) and crystal densities (1.575 cf. 1.586 g/cm ³ ).