Crystal structure, quantum chemical insights, and molecular docking studies of Naryl-2-(N-disubstituted) acetamide compounds: potential inhibitors for neurodegenerative enzymes.

The increase in and concern about neurodegenerative diseases continue to grow in an increasingly long-lived world population. Therefore, the search for new drugs continues to be a priority for medicinal chemistry. We present here the synthesis of a series of compounds with acetamide nuclei. Their structures were established using UV-Visible, NMR, HRMS and IR techniques. Furthermore, we report the crystal structures that were obtained from compounds 5a-5d by X-ray diffraction. The compounds were evaluated as potential inhibitors of the monoxidase enzymes; A (MAO-A) and B (MAO-B), and cholinesterases; acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) through in silico studies using the induced fit docking (IFD) method and binding free energy (ΔGbind) calculations by the MMGBSA method. Interestingly, compounds 5b, 5c and 5d showed much better ΔGbind than the reference drug Zonisamide. Compound 5c is the best in the series, which indicates a potential selective affinity of our compounds against MAO-B, which could be a promising finding in the search for new drugs for Parkinson's disease treatment. The acetamide crystal exhibits moderate NLO properties suggesting that it could be considered a potential candidate for application in nonlinear optical devices.

O-Alkyl derivatives of ferulic and syringic acid as lipophilic antioxidants: effect of the length of the alkyl chain on the improvement of the thermo-oxidative stability of sunflower oil.

Lipid oxidation is the major cause of the deterioration of fat-containing foods, especially those containing polyunsaturated fatty acids (PUFAs). Antioxidant additives of synthetic origin are added to matrices rich in PUFAs, such as sunflower oil (SO). However, there is controversy regarding their safety, and their low solubility in both water and fat has led to the search for new covalent modifications through lipophilicity. This work presents the synthesis of O-alkyl acid derivatives from ferulic and syringic acids and the study of their antioxidant capacity and effect on the thermoxidative degradation of SO. Antioxidant activities were evaluated by employing ferric reducing antioxidant power (FRAP) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assays in a concentration range of 10-100 µg mL-1. The IC50 values for DPPH scavenging activity ranged from 15.61-90.43 µg mL-1. The results of the FRAP assay for both O-alkyl ferulic (3a-f) and syringic (5a-f) series revealed a "cut-off" effect on antioxidant activity in carbon five (C5). Thermoxidation study of additives 3b-c and 5b-c showed a decrease in the slope of extinction coefficients K 232 and K 270 in comparison with SOcontrol. Furthermore, 3c presented higher antioxidant activity than 3b and 1, with a power to decrease the thiobarbituric acid reactive species (TBARS) 6 times higher than SOcontrol at 220 °C. Additives 5b-c exerted a protective effect on the thermoxidation of SO. The results suggest that increasing lipophilic and thermal properties of antioxidants through O-alkyl acid derivatization is an effective strategy for accessing lipophilic antioxidant additives with potential use in food matrices.

Design, synthesis, theoretical study, antioxidant, and anticholinesterase activities of new pyrazolo-fused phenanthrolines.

Pyrazole-fused phenanthroline compounds were obtained through several synthetic routes. NMR, HRMS, and IR techniques were used to characterize and confirm the chemical structures. Crystal structures were obtained from compounds 3a, 5b, 5j, 5k, and 5n and analyzed using X-ray diffraction. Compounds were evaluated as acetyl (AChE) and butyrylcholinesterase (BChE) inhibitors, and the results showed a moderate activity. Compound 5c presented the best activity against AChE (IC50 = 53.29 µM) and compound 5l against BChE enzyme (IC50 = 119.3 µM). Furthermore, the ability of the synthetic compounds to scavenge cationic radicals DPPH and ABTS was evaluated. Compound 5e (EC50 = 26.71 µg mL-1) presented the best results in the DPPH assay, and compounds 5e, 5f and 5g (EC50 = 11.51, 3.10 and <3 µg mL-1, respectively) showed better ABTS cationic radical scavenging results. Finally, in silico analyses indicated that 71% of the compounds show good oral availability and are within the ranges established by the Lipinski criteria.