ACHE x α-glucosidase

Lespedeza bicolour Turcz. is a traditional medicinal plant with a wide range of ethnomedicinal values. The main components of L. bicolour essential oil (EO) were β-pinene (15.41%), β-phellandrene (12.43%), and caryophyllene (7.79%). The EO of L. bicolour showed antioxidant activity against ABTS radical and DPPH radical with an IC₅₀ value of 0.69 ± 0.03 mg/mL and 10.44 ± 2.09 mg/mL, respectively. The FRAP antioxidant value was 81.96 ± 6.17 μmol/g. The EO had activities against acetylcholinesterase, α-glucosidase, and β-lactamase with IC₅₀ values of 309.30 ± 11.16 μg/mL, 360.47 ± 35.67 μg/mL, and 27.54 ± 1.21 μg/mL, respectively. Molecular docking showed methyl dehydroabietate docked well with all tested enzymes. Sclareol and (+)-borneol acetate showed the strongest binding affinity to α-glucosidase and β-lactamase, respectively. The present study provides a direction for searching enzyme inhibitors for three tested enzymes and shows L. bicolour EO possesses the potential to treat a series of diseases.

Chili peppers have been under the spotlight of bioactivity research as they feature a diverse and rich phytochemical profile with multiple health promoting effects. These beneficial properties are related to the chemical composition of chili peppers and is of utmost importance to identify varieties with the strongest bioprospecting potential. In this study, 19 chili pepper varieties were investigated originating from Capsicum annuum L. (n = 3), Capsicum baccatum L. (n = 3) and Capsicum chinense Jacq. (n = 13) species. Firstly, a suspect screening based on a spectral library was applied and the bioactive profile of all samples was acquired using ultra-high-performance liquid chromatography hybrid quadrupole time-of-flight mass spectrometry (UHPLC-q-TOF-MS). The ethanolic extracts were richer in bioactive compounds and exhibited the highest antioxidant capacity. Then, 6 different enzyme assays were performed targeting enzymes involved in non-communicable diseases, such as cholinesterases involved in Alzheimer's disease or pancreatic lipase in obesity. The strongest inhibitory effect was noticed for 6 Capsicum chinense Jacq. varieties (half maximal inhibitory concentration ranging between 0.56 and 9.2 mg/mL), namely Moruga, Naga chocolate, Bhut jolokia, Carolina reaper, Trinidad scorpion moruga and Naga morich. By using the enzyme inhibitory profile, it was feasible to discriminate these 6 varieties from the rest tested based on a principal component analysis (PCA) model. Moderate and strong correlations were also noticed between the relative content of the identified compounds and the enzyme inhibition. Naringenin, a flavanone, and vanillic acid, a phenolic acid, strongly correlated towards human acetylcholinesterase and alpha glucosidase inhibition, respectively. Overall, the presented results underscore the high potential of Capsicum chinense Jacq. species to be used as sources of bioactive natural compounds for nutraceutical applications.

A series of new hybrid styrylchromone (3a-3h) molecules incorporating imidazole and chromone nuclei were synthesized and characterized. A Diels-Alder cycloaddition reaction was performed on these compounds, leading to the formation of a new series of tricyclic molecules (4a-4h). The evaluation of their biological activity revealed that the cyclization of the styrylchromones significantly enhances their bioactive potential, in particular their inhibitory capacity towards acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and α-glucosidase enzymes. Among the tested compounds, derivative 4c exhibited the most promising inhibitory activity against both AChE (3.93 μM) and α-glucosidase (9.61 μM), with an efficacy comparable to or even exceeding that of the standard inhibitors tacrine and acarbose. This compound also showed remarkable inhibition of BChE enzyme with an IC₅₀ of 9.41 μM. Furthermore, derivative 4a was identified as the most potent inhibitor of this enzyme, displaying an activity approximately two times greater than that of tacrine (IC₅₀ 10.01 vs 22.30 nM). In silico studies, including molecular docking and DFT calculations, were conducted to better understand the interaction modes between the synthesized molecules and their target enzymes, as well as the reaction mechanism underlying their synthesis. Overall, the results of this study highlight the therapeutic potential of the synthesized compounds, particularly the cyclized derivatives.