Diabetes mellitus is a major health problem globally. The management of carbohydrate digestion provides an alternative treatment. Flavonoids constitute the largest group of polyphenolic compounds, produced by plants widely consumed as food and/or used for therapeutic purposes. As such, isoxazoles have attracted the attention of medicinal chemists by dint of their considerable bioactivity. Thus, the main goal of this work was to discover new hybrid molecules with properties of both flavonoids and isoxazoles in order to control carbohydrate digestion. Moreover, the trifluoromethyl group is a key entity in drug development, due to its strong lipophilicity and metabolic stability. Therefore, the present work describes the condensation of a previously synthesized trifluoromethylated flavonol with different aryl nitrile oxides, affording 13 hybrid molecules indicated as trifluoromethylated flavonoid-based isoxazoles. The structures of the obtained compounds were deduced from by ¹H NMR, ¹³C NMR, and HRMS analysis. The 15 newly synthesized compounds inhibited the activity of α-amylase with an efficacy ranging from 64.5 ± 0.7% to 94.7 ± 1.2% at a concentration of 50 μM, and with IC₅₀ values of 12.6 ± 0.2 μM–27.6 ± 1.1 μM. The most effective compounds in terms of efficacy and potency were 3b, 3h, 3j, and 3m. Among the new trifluoromethylated flavonoid-based isoxazoles, the compound 3b was the most effective inhibitor of α-amylase activity (PI = 94.7 ± 1.2% at 50 μM), with a potency (IC₅₀ = 12.6 ± 0.2 μM) similar to that of the positive control acarbose (IC₅₀ = 12.4 ± 0.1 μM). The study of the structure–activity relationship based on the molecular docking analysis showed a low binding energy, a correct mode of interaction in the active pocket of the target enzyme, and an ability to interact with the key residues of glycosidic cleavage (GLU-230 and ASP-206), explaining the inhibitory effects of α-amylase established by several derivatives.

Plants offer a bountiful source of natural pest control solutions through their essential oils. This research introduces and analyzes an eco-friendly natural essential oil for red flour beetle control. Therefore, the current study was included to show the chemical profile and the insecticidal efficacy of resin essential oil (REO) and its fractions (F_1–3), resulting from chromatographic separation, from the plant Schinus molle against Tribolium castaneum adults. The trunk bark resin essential oil and its fractions’ composition were analyzed by GC-MS. Overall, 33 constituents with 98.3% of the total EO composition were identified. REO and F_1–3 displayed impressive repellent properties at a concentration of 0.12 µL/cm². After 120 min of exposure, repellency ranged from 73.3% to a remarkable 96.7%. They also exhibited noteworthy fumigant properties, with median lethal doses of LD₅₀ = 120.6–160.8 μL/L. The fractions F₁ and F₃ showed the most notable topical toxicity at a concentration of 10%, with LD₅₀ values of 8.6% and 5.6%, respectively. Fractions F₃ and F₂ demonstrated the most effective inhibition of acetylcholinesterase (AChE) activity, providing insight into their insecticidal mechanisms. The in silico molecular docking and DFT studies corroborate the results of in vitro tests performed to identify new insecticide products derived from natural sources.