N-Substituted piperidine-3-carbohydrazide-hydrazones against Alzheimer's disease: Synthesis and evaluation of cholinesterase, beta-amyloid inhibitory activity, and antioxidant capacity.

A series of piperidine-3-carbohydrazide-hydrazones bearing phenylethyl, phenylpropyl, and phenylbutyl substituents on piperidine nitrogen were designed and synthesized as cholinesterase (ChE) inhibitors. The title compounds were screened for acetylcholinesterase (AChE), butyrylcholinesterase (BuChE) inhibitory activities and antioxidant capacities, and the active ones for Aß42 self-aggregation inhibition, in vitro. The chemiluminescence method was used to determine the effect of the selected compounds on the reactive oxygen species (ROS) levels in brain tissue. Physicochemical properties were calculated by the MOE program. Kinetic analysis and molecular modeling studies were also carried out for the most active compounds. Generally, the final compounds exhibited moderate to good AChE or BuChE inhibitory activity. Among them, 3g and 3j showed the most potent activity against AChE (IC50 = 4.32 µM) and BuChE (IC50 = 1.27 µM), respectively. The kinetic results showed that both compounds exhibited mixed-type inhibition. Among the selected compounds, nitro derivatives (3g, 4g, and 5g) provided better Aß42 inhibition. According to the chemiluminescence assay, 4i exhibited the most active superoxide free-radical scavenger activity and 3g, 3j, and 4i showed similar scavenger activity on other ROS. All results suggested that 3g, 3j, and 4i have good AChE/BuChE, Aß42 inhibitory potentials and antioxidant capacities and can therefore be suggested as promising multifunctional agents to combat Alzheimer's disease.

Are Some Metals in Tattoo Inks Harmful to Health? An Analytical Approach.

Tattoo application is widely performed all over the world; however, injection of coloring substances into the skin as metals may pose a risk for allergies and other skin inflammations and systemic diseases. In this context, tattoo inks in green, black, and red colors of three brands were purchased. Before starting the analysis, the acid mixture suitable for microwave burning was determined, and according to these results, the inks were digested with nitric acid, hydrochloric acid, and hydrofluoric acid. Then, method validation was performed for tattoo inks using inductively coupled plasma-mass spectrometry. The relative contribution of metals to the tattoo ink composition was highly variable between colors and brands. Elements found in the main components of inks are as follows (in mg kg-1): Al, 1191.1-3424.9; Co, 0.04-1.07; Cu, 1.24-2523.4; Fe, 16.98-318.42; Ni, 0.63-17.53; and Zn, 2.6-46.9. It has been determined by the Environmental Protection Agency that in some products, especially the copper element is above the determined limit. The analysis results obtained were classified by chemometric analysis, and the color and brand relationship were determined. More toxicological studies are necessary to understand the effects of tattoo inks containing heavy metals and/or organic components.

Synthesis, bioactivity and molecular modeling studies on potential anti-Alzheimer piperidinehydrazide-hydrazones.

A group of N-benzylpiperidine-3/4-carbohydrazide-hydrazones were designed, synthesized and evaluated for acetylcholinesterase (AChE), butyrylcholinesterase (BuChE) activities, Aß42 self-aggregation inhibitory potentials, and antioxidant capacities, in vitro. All of the compounds displayed eeAChE and huAChE inhibitory activity in a range of IC50 = 5.68-11.35 µM and IC50 = 8.80-74.40 µM, respectively and most of the compounds exhibited good to moderate inhibitory activity on BuChE enzyme. Kinetic analysis and molecular modeling studies were also performed for the most potent compounds (1g and 1j). Not only the molecular modeling studies but also the kinetic analysis suggested that these compounds might be able to interact with the catalytic active site (CAS) and the peripheral anionic site (PAS) of the enzymes. In the light of the results, compound 1g and compound 1j may be suggested as lead compounds for multifunctional therapy of AD.