Synthesis and biological evaluation of potential acetylcholinesterase inhibitors based on a benzoxazine core.

With the purpose of expanding the structural variety of chemical compounds available as pharmacological tools for the treatment of Alzheimer's disease, we synthesized and evaluated a novel series of indole-benzoxazinones (Family I) and benzoxazine-arylpiperazine derivatives (Family II) for potential human acetylcholinesterase (hAChE) inhibitory properties. The most active compounds 7a and 7d demonstrated effective inhibitory profiles with Ki values of 20.3 ± 0.9 µM and 20.2 ± 0.9 µM, respectively. Kinetic inhibition assays showed non-competitive inhibition of AChE by the tested compounds. According to our docking studies, the most active compounds from both series (Families I and II) showed a binding mode similar to donepezil and interact with the same residues.

Evaluation of the generation of reactive oxygen species and antibacterial activity of honey as a function of its phenolic and mineral composition.

The antibacterial activity (ABA) of honey is associated with the generation of reactive oxygen species (ROS), where polyphenols (PFs) play a key role due to their pro-oxidant action modulated by metallic cations. In this work, the contents of PFs, H2O2, OH radicals, Cu, Fe, Mn, Zn, and ABA against Staphylococcus epidermidis and Pseudomonas aeruginosa were determined in honeys from central Chile. Then, their relationships were evaluated through partial least squares regression. The average contents of phenolic acids, flavonoids and metals in honey ranged from 0.4 to 4 µg/g, 0.3-1.5 µg/g and 3-6 µg/g, respectively. All honeys showed accumulation of H2O2 (1-35 µg/g) and OH radicals. The PLS showed that gallic acid, p-coumaric acid, chrysin, kaempferol, Fe, and Mn stimulate the generation of ROS. Quercetin, Cu, and Zn showed marginal antioxidant effects. PFs favor the ABA of honey against both bacteria and H2O2 against S. epidermidis.

Antioxidant Compound Adsorption in Polyvinylpolypyrrolidone from Chilean Carménère, Cabernet Sauvignon, and Merlot Grape Pomaces as Potential By-Products.

Grape pomace (GP) is a by-product resulting from the winemaking process and its potential use as a source of bioactive compounds is well known. The GP bioactive compounds can be retained in the well-known polyvinylpolypyrrolidone (PVPP), industrially used in the clarification and stabilization of wine and other drinks. Thus, the polyphenolic compounds (PC) from the Chilean Carménère, Cabernet Sauvignon, and Merlot GP were extracted, and their compositions and antioxidant capacities (ORAC-FL) were determined. In addition, the retention capacity of the PC on PVPP (PC-PVPP) was evaluated. The bioactivities of GP extracts and PC-PVPP were estimated by the agar plate inhibition assay against pathogenic microorganisms. Results showed a high amount of TPC and antioxidant capacity in the three ethanolic GPs extracts. Anthocyanins, flavan-3-ol, and flavonols were the most abundant compounds in the GP extract, with retentions between 70 and 99% on PVPP. The GP extracts showed inhibition activity against B. cereus and P. syringae pv. actinidiae but the GP-PVPP had no antimicrobial activity. The high affinity of the identified PCs from GPs on PVPP polymer could allow the design of new processes and by-products for the food or cosmeceutical industry, promoting a circular economy by reducing and reusing wastes (GPs and PVPP) and organic solvents.

Evaluation of the Novel Antichagasic Activity of [1,2,3]Triazolo[1,5-a]pyridine Derivatives.

BACKGROUND: Trypanosoma cruzi is the causative agent of Chagas disease. This parasite is vulnerable to the effects of ROS as its main defense mechanism against exogenous agents trypanothione is also another weakness of the parasite that investigated related to the inhibition of enzymes belonging P450 system, mainly CYP51. In our group we have synthesized a series of triazoles known as [1,2,3]triazolo[1,5-a]pyridyl ketones, and pyridyl ketones. These families have shown interesting structural features due to the presence of electron withdrawing moieties attached to the main heterocycle (triazoles and/or pyridines) and are proposed as potential target in the parasite, by the presence of the carbonyl group being able to be reduced and form a free radical that could interact with molecular oxygen generating ROS in the parasite. Furthermore, the triazole ring and pyridines have been considered as potent inhibitors of sterol biosynthesis, the lock being part CYP51. RESULT: Our results showed that the series is capable of generating a stable radical species and generate ROS in the parasite. On the other hand these molecules are potent inhibitors of enzymes belonging to the complex P450. We have focused on the inhibition of ergosterol biosynthesis demonstrating that triazole/ pyridine families are able to affect this pathway being observed the accumulation of squalene and lanosterol.

Spin trapping: an essential tool for the study of diseases caused by oxidative stress.

Electron spin resonance (ESR), called also electron paramagnetic resonance (EPR) together with the spin trapping technique, has allowed us to study and understand how free radicals are involved in various pathologies. In this review, the importance of spin trapping technique in the study of diseases such as cancer, diabetes, hypertension and parasitic diseases is discussed. In addition, advances in the use of this technique as therapeutic agents and other interesting applications as the immuno-spin trapping technique are reviewed.