Discovery of novel dual-active 3-(4-(dimethylamino)phenyl)-7-aminoalcoxy-coumarin as potent and selective acetylcholinesterase inhibitor and antioxidant.

A series of 3-substituted-7-aminoalcoxy-coumarin was designed and evaluated as cholinesterase inhibitors and antioxidants. All compounds were effective in inhibiting AChE with potencies in the nanomolar range. The 3-(4-(dimethylamino)phenyl)-7-aminoethoxy-coumarin (6a) was considered a hit, showing good AChE inhibition potency (IC50 = 20 nM) and selectivity (IC50 BuChE/AChE = 354), quite similar to the reference drug donepezil (IC50 = 6 nM; IC50 BuChE/AChE = 365), also presenting antioxidant properties, low citotoxicity and good-predicted ADMET properties. The mode of action (mixed-type) and SAR analysis for this series of compounds were described by means of kinetic and molecular modeling evaluations.

Countercurrent chromatography isolation of green propolis biomarkers: Potential blockers of SARS-COV-2 RBD and ACE2 interaction.

Propolis is a natural resinous mixture produced by honeybees with numerous biological activities. Considering the recently reported potential of propolis as an adjuvant in COVID-19 treatment, a methodology for the fractionation of the hexane extract of Brazilian green propolis (HEGP) was developed for the obtention of prenylated biomarkers by countercurrent chromatography. The inhibition of the interaction between the receptor binding domain (RBD) of spike and ACE2 receptor was evaluated by the Lumitᵀᴹ immunoassay. Fractionation of HEGP was performed by both normal (CCC1 and CCC2, with extended elution) and reversed (CCC3) phase elution-extrusion modes with the solvent system hexane-ethanol-water 4:3:1. The normal elution mode of CCC1 (471 mg HEGP in a 80 mL column volume, 1.6 mm id) was scaled-up (CCC5, 1211 mg HEGP in a 112 mL column volume, 2.1 mm id), leading to the isolation of 89.9 mg of artepillin C, 1; 52.7 mg of baccharin, 2; and 26.6 mg of chromene, with purities of 93 %, 83 % and 88 %, respectively, by HPLC-PDA. Among the isolated compounds, artepillin C, 1, and baccharin, 2, presented the best results in the Lumitᵀᴹ immunoassay, showing 67% and 51% inhibition, respectively, at the concentration of 10 µM. This technique proved to be of low operational cost and excellent reproducibility.

Persea americana Mill.: Evaluation of cytogenotoxicity and phytochemical prospection of leaf extracts

Abstract Persea americana Mill., belonging to the family Lauraceae, is noteworthy for the large amount of ethnopharmacological information in its regard, attributing to it many and varied medicinal properties. The tea and alcoholic extracts made from its leaves are used in folk medicine to treat various ailments. This study was designed to analyze the cytogenotoxicity and underlying chemistry of aqueous and hydroalcoholic extracts of avocado leaves, using the Allium cepa and micronucleus tests. The results obtained by applying the experimental models demonstrate that the extracts did not have a genotoxic effect at any of the concentrations analyzed, and even demonstrated a certain protective effect, possibly due to the presence of flavonoids and phenols, both of which are antioxidant substances. However, the extracts did present a cytotoxic effect. There were numerous karyorrhectic cells and those with nuclear alterations related to cell death. At the highest concentrations, it was possible to observe cytoplasmic alterations and binucleated cells. The extracts also caused a significant reduction in the number of cells undergoing division. These effects can be a response to the phytochemical agents present in the extracts. The results suggest that the extracts contain bioactive components that deserve further studies related to cancer therapies.