A series of novel multi-substituted coumarin derivatives were synthesized, spectroscopically characterized, and evaluated for their antioxidant activity, soybean lipoxygenase (LOX) inhibitory ability, their influence on cell viability in immortalized human keratinocytes (HaCaT), and cytotoxicity in adenocarcinomic human alveolar basal epithelial cells (A549) and human melanoma (A375) cells, in vitro. Coumarin analogues 4a–4f, bearing a hydroxyl group at position 5 of the coumarin scaffold and halogen substituents at the 3-phenyl ring, were the most promising ABTS^•+ scavengers. 6,8-Dibromo-3-(4-hydroxyphenyl)-4-methyl-chromen-2-one (4k) and 6-bromo-3-(4,5-diacetyloxyphenyl)-4-methyl-chromen-2-one (3m) exhibited significant lipid peroxidation inhibitory activity (IC₅₀ 36.9 and 37.1 μM). In the DCF-DA assay, the 4′-fluoro-substituted compound 3f (100%), and the 6-bromo substituted compounds 3i (80.9%) and 4i (100%) presented the highest activity. The 3′-fluoro-substituted coumarins 3e and 4e, along with 3-(4-acetyloxyphenyl)-6,8-dibromo-4-methyl-chromen-2-one (3k), were the most potent lipoxygenase (LOX) inhibitors (IC₅₀ 11.4, 4.1, and 8.7 μM, respectively) while displaying remarkable hydroxyl radical scavenging ability, 85.2%, 100%, and 92.9%, respectively. In silico docking studies of compounds 4e and 3k, revealed that they present allosteric interactions with the enzyme. The majority of the analogues (100 μΜ) did not affect the cell viability of HaCaT cells, though several compounds presented over 60% cytotoxicity in A549 or A375 cells. Finally, the human oral absorption (%HOA) and plasma protein binding (%PPB) properties of the synthesized coumarins were also estimated using biomimetic chromatography, and all compounds presented high %HOA (>99%) and %PPB (60–97%) values.

The encapsulation of clove essential oil (CEO) in hydroxypropyl-β-cyclodextrin (HP-β-CD) and the subsequent incorporation of the inclusion complex in an elastic chitosan film in order to achieve a controlled release profile of the volatile CEO are herein presented. Freshly distilled CEO was found to contain eugenol in concentrations higher than 70%. The kneading method was implemented for the preparation of a CEO-HP-β-CD inclusion complex, resulting in a 50% inclusion efficiency of the essential oil in particles sized 214.40 nm with ζ-potential −27.5 mV. Free CEO and CEO-HP-β-CD inclusion complex were tested for their ability to scavenge the 2,2-Diphenyl-1-picrylhydrazyl (DPPH) radical, and it was found that the CEO-HP-β-CD complex presented enhanced antioxidant activity (88%) compared to the free CEO (71%). Choline chloride-containing chitosan (CS) films were prepared, incorporating either the pure CEO or the CEO-HP-β-CD inclusion complex, and their mechanical properties were determined. The study of the release profile in different pH values demonstrated the capacity of the CS-HP-β-CD system to provide sustained release of CEO, noting its potential use in food processing as smart packaging.

The aim of the present study was the encapsulation of cedar (Juniperus phoenicea) essential oil (CEO) of Greek origin in β-cyclodextrin (β-CD) through the formation of inclusion complexes (ICs) using the co-precipitation method with different β-CD-to-CEO weight ratios (90:10, 85:15, 80:20, 70:30 (w/w)). The encapsulation of CEO in β-CD through host–guest interactions was confirmed by Nuclear Magnetic Resonance (NMR) spectroscopy, FT-IR spectroscopy, Differential Scanning Calorimetry (DSC) and Thermogravimetric Analysis (TGA). The obtained ICs exhibited nanoscale size (315.9 nm to 769.6 nm),Polydispersity Index from 0.326 to 0.604 and satisfactory stability in suspension (−37.0 mV to −17.0 mV). The process yield was satisfactory, ranging between 65% and 78%, while the inclusion efficiency ranged from 10% to 27%. The in vitro release study conducted for the IC with the optimal characteristics (β-CD:CEO 80:20 (w/w)) exhibited a sustained release profile, with an initial burst effect in the first 5 h. The release profile could be well expressed by the Higuchi equation: Q = 18.893 t^1/2 + 9.5919, R² = 0.8491. The cedar EO presented significant acetylcholinesterase inhibition (IC₅₀ 37 μg/mL), which was prolonged by its encapsulation into the β-CD cavity.

In this work, the preparation of inclusion complexes, (ICs) using magnesium phthalocyanine (MgPc) and various cyclodextrins (β-CD, γ-CD, HP-β-CD, Me-β-CD), using the kneading method is presented. Dynamic light scattering (DLS) indicated that the particles in dispersion possessed mean size values between 564 to 748 nm. The structural characterization of the ICs by infrared spectroscopy (FT-IR) and nuclear magnetic resonance (NMR) spectroscopy provides evidence of the formation of the ICs. The release study of the MgPc from the different complexes was conducted at pH 7.4 and 37 °C, and indicated that a rapid release (“burst effect”) of ~70% of the phthalocyanine occurred in the first 20 min. The kinetic model that best describes the release profile is the Korsmeyer–Peppas. The photodynamic therapy studies against the squamous carcinoma A431 cell line indicated a potent photosensitizing activity of MgPc (33% cell viability after irradiation for 3 min with 18 mW/cm²), while the ICs also presented significant activity. Among the different ICs, the γ-CD-MgPc IC exhibited the highest photokilling capacity under the same conditions (cell viability 26%). Finally, intracellular localization studies indicated the enhanced cellular uptake of MgPc after incubation of the cells with the γ-CD-MgPc complex for 4 h compared to MgPc in its free form.

A ligand-free approach for the Suzuki-Miyaura cross coupling reaction using Natural Deep Eutectic Solvents (NaDES) towards coumarin analogs is described. A model reaction between the synthetically prepared 3-(4-acetyloxy-phenyl)-6-bromo-4-methyl-coumarin (3b) and phenylboronic acid was performed in five different NaDES as well as in pure glycerol, using two inorganic bases and palladium catalysts. The reaction proceeded smoothly in Choline Chloride/Glycerol (ChCl/Gly) and Betaine/Glycerol (Bet/Gly) NaDES at 90 °C in 24 h, affording the desired product in high yields up to 95%. The combination of K₂CO₃, Pd(OAc)₂ and ChCl/Gly NaDES provided optimum yields and high purity of the desired compounds, while the solvent was successfully recycled and reused up to two times. The developed methodology is applicable to boronic acids bearing various substituents. The formation of palladium nanoparticles in the reaction mixture was observed, and the size of the nanoparticles was associated with the reaction yield. In addition, in all the glycerol-based NaDES, an effective removal of the acetyl group of the acetyloxy–coumarin analogs was observed; thus, it is noteworthy that the Suzuki–Miyaura coupling and the deacetylation reaction were achieved in one pot. The ten novel coumarin derivatives synthesized were structurally characterized using 1D and 2D NMR spectroscopy and were tested for their cytotoxicity against the A431 squamous cancer cell line, presenting significant activity.