The aim of the present research is the evaluation of the extraction process effect on the chemical composition, the antioxidant activities, and the mild steel corrosion inhibition ability of Argania spinosa’s extracts (alimentary oil (AO) and hexanic extract of roasted almonds (HERA)). The chemical composition revealed that both extracts have the same major compounds: Palmitic, linoleic, and stearic acids, with their order slightly different. Electrochemical impedance spectroscopy (EIS), weight loss measurements, and polarization curves were used to estimate AO and HERA’s mild steel corrosion’s inhibition capacity. Based on these three methods, AO registered, respectively, 81%, 87%, and 87% inhibition efficiency while HERA registered 78%, 84%, and 82% inhibition efficiency. The antioxidant activity of AO and HERA was examined in parallel with standard antioxidants (gallic acid and quercetin) using two assays: DPPH* scavenging assay and ferric reducing antioxidant power assay (FRAP). AO had less EC₅₀ in both techniques (DPPH*: 3559.08 ± 161.75 μg/mL; FRAP 1288.58 ± 169.21 μg/mL) than HERA (DPPH*: 3621.43 ± 316.05 μg/mL; FRAP 1655.86 ± 240.18 μg/mL). Quantum chemical and molecular dynamic studies were employed to suggest the adsorption mechanism.

A new series of acetylated (6a-b and 8a-b) and alkylated (7a-b) derivatives of pyran-3-ylidène -1,5-benzodiazepine have been synthesized through a three-step process. The starting compounds (5a and 5b) were created by reacting o-phenylenediamine with dehydroacetic acid under reflux in ethanol. This reaction produced the intermediate imine (3), which was then cyclized with aromatic aldehydes. Since derivatives 5a and 5b possess two NH groups at positions 1 and 5, functionalization with acyl and aliphatic groups was accomplished. The acetylation reaction used acetic and propionic anhydrides, yielding primarily monoa-cetylated compounds (6a-b and 8a-b). The alkylation of derivative 5a was performed under phase transfer catalysis, resulting in monoalkylated products (7a-b). The synthesized pyrano-1,5-benzodiazepine derivatives were characterized using NMR spectroscopy. Additionally, some pyran-3-ylidène -1,5-benzodiazepine com-pounds (5b, 6b, 7b, 8a and 8b) were analyzed via single-crystal X-ray diffraction. The HF surface analysis em-ployed metrics such as dnorm, de/di indices, curvedness, and fragment patches to provide detailed visualizations of electron density and interactions. The 2D fingerprint plots indicated that the dominant interaction was H●●H, along with several secondary interactions. Molecular docking studies assessed the binding affinities of different benzodiazepine derivatives to the GABA receptor (PDB: 6HUP), using Valium as a reference. All compounds demonstrated superior binding affinities compared to Valium, with compound 8a identified as the most potent inhibitor, exhibiting a binding energy of -7.928 kcal/mol due to favorable n-π and π-π interactions with crucial amino acids Met286 and Pro233. Time-dependent density functional theory (TD-DFT) calculations revealed that compounds 8a and 6a had the lowest energy gaps and reactivity indices closely aligned with Valium. Molecular electrostatic potential maps displayed strong negative potentials over carbonyl oxygens and diazepine nitrogen, suggesting significant interactions with receptors. The ADMET profile indicated that most compounds adhered to Lipinski’s rules exhibited acceptable Caco-2 permeability, and had low hepatotoxicity and carcinogenic risks. Both gastrointestinal absorption and blood-brain barrier permeability were favorable, and the synthetic accessibility scores were higher than Valium's. High passive MDCK permeability and the absence of mutagenicity further affirmed the developmental potential of these compounds. Compounds 5b, 6a, 6b, 7b, 8a and 8b demonstrated enhanced profiles for advancement as clinical candidates based on in silico predictions, warranting further experimental validation.