In Silico Interactions of the Components from the Schinus terebinthifolius Extract with Human Tyrosinase.

The anti-tyrosinase activity of the leaf extract of Schinus terebinthifolius, also known as Brazilian peppertree, was evaluated using multiple in silico approaches, such as molecular homology, molecular docking, MM-GBSA, molecular dynamics, MM-PBSA, QSAR, and skin permeability predictions. With these computational tools, the compounds that downregulate tyrosinase enzyme activity could be evaluated, and more potent molecules could be identified. The results indicated that various compounds, especially luteolin, are accountable for the anti-tyrosinase activity of S. terebinthifolius. For cosmetic application, further studies with luteolin are especially recommended, for having presented a good performance both in theoretical inhibition (30.92 kJ mol-1 ) and skin permeability (LogKp=-6.62 cm-1 ).

Synthesis and evaluation of a pentafluorobenzamide stationary phase for HPLC separations in the reversed phase and hydrophilic interaction modes.

A pentafluorobenzamide stationary phase was synthesized by an easy method with no intermediate purification steps. Physicochemical characterization (elemental analysis, fourier transform infrared spectroscopy, 29 Si and 13 C nuclear magnetic resonance spectroscopy) confirmed the presence of pentafluorobenzamide functionalization on the surface of the silica particles. The pentafluorobenzamide stationary phase proved to be quite versatile as it can be used in two different modes in liquid chromatography: reversed phase and hydrophilic interaction liquid chromatography. Chromatographic characterizations in both modes confirmed the multiple interactions established by the new stationary phase, such as hydrogen bonding and π-π and ion-exchange interactions. The pentafluorobenzamide stationary phase was successfully employed for the separation of nucleosides and antihypertensive drugs under hydrophilic interaction liquid chromatography conditions, as well as pesticides and benzodiazepine using reversed phase conditions. The stationary phase showed significant potential when compared with commercial columns.

Discovery of novel dual acetylcholinesterase inhibitors with antifibrillogenic activity related to Alzheimer's disease.

AIM: Alzheimer's disease is a progressive and neurodegenerative disorder of the CNS, affecting elderly people. The current pharmacological approach is based on the improvement of cholinergic neurotransmission by inhibiting acetylcholinesterase (AChE) with AChE inhibitors. The disease is also characterized by the accelerated accumulation of ß-amyloid plaques around neurons. Furthermore, in vitro studies revealed that AChE can induce ß-amyloid peptide (Aß) aggregation. METHODOLOGY: Computer-aided molecular design by virtual screening was here employed to discover novel potential AChE inhibitors, with antifibrillogenic properties, in other words, inhibiting Aß aggregation. RESULTS: Compounds 1, 4 and 6 showed interesting AChE inhibition. In addition, they particularly inhibit Aß aggregation in vitro, indicating to be promising novel anti-Alzheimer agents.

2-Aryl-3-(2-morpholinoethyl)thiazolidin-4-ones: Synthesis, anti-inflammatory in vivo, cytotoxicity in vitro and molecular docking studies.

Seven new 4-thiazolidinones bearing the morpholino moiety were easily synthesized by one-pot reactions of 4-(2-aminoethyl)morpholine (2-morpholinoethylamine), arenealdehydes and mercaptoacetic acid refluxing toluene for 19 h with moderate to good yields (45-97%). These novel compounds were fully identified and characterized by NMR spectroscopy and mass spectrometry. Thiazolidin-4-ones in vivo anti-inflammatory activities were determined using a croton oil-induced ear edema model of inflammation in BALB C mice. The best results were found for compounds 4c (49.20 mmol/kg), 4d (49.20 mmol/kg) and 4f (52.48 mmol/kg), which showed the ability to decrease the ear edema in mice by 50%, 48% and 54%, respectively, when compared to the standard drug indomethacin. In addition, the in vitro cytotoxicity activity of thiazolidin-4-ones against Vero cells was also performed and four compounds (4a, 4c, 4d and 4f) showed no toxic effect at 500 µg/mL. A docking simulation of compounds into the 1Q4G (COX-1) and 4PH9 (COX-2) enzymes binding site was conducted. This preliminary result will guide us in for further studies to improve the anti-inflammatory activity.