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Natural compounds from marine organisms have been rarely studied for their acetylcholinesterase inhibitory activities. The aim of this study was to isolate novel compounds with antiAChE activity from the venom of upside-down jellyfish Cassiopea andromeda Forskål, 1775. The compounds of the fractionated venom on gel filtration chromatography were identified by analyzing gas chromatography–mass spectroscopy data. The structure of the isolated compound that showed the most potent antiAChE activity in a docking study was elucidated by different spectral data, including 1H NMR and 13C NMR. Three compounds, including a neurosteroidal alkaloid androtoxin B, were identified from two venom fractions. This neurosteroidal alkaloid showed strong acetylcholinesterase inhibitory activity (IC50 2.24 ± 0.1 μM) compared with the reference standard, galantamine. The results obtained by a docking study demonstrated that Androtoxin B had close contact with two of the three amino acid residues of the catalytic triad of acetylcholinesterase gorge and was accommodated within a peripheral hydrophobic pocket composed of numerous aromatic site chains. In conclusion, the isolated neurosteroidal alkaloid from Cassiopea andromeda was a potent antiAChE agent with strong binding to both the catalytic and peripheral sites of acetylcholinesterase that correlated well with the experimental data. Further studies are required to determine whether androtoxin B could be a potential treatment for Alzheimer's disease. Keywords: Upside-down jellyfish, Antiacetylcholinesterase activity, Androtoxin B, Alzheimer's disease, Neurosteroidal alkaloid, GABA-A receptor

The synthesis of a new series of imidazo[2,1-b]thiazole derivatives is described. They were tested as potential acetylcholinesterase and butyrylcholinesterase inhibitors by means of a chemiluminescent microassay. Although most of the new compounds did not show significant cholinesterase inhibition potency, three of them displayed selective antiacetylcholinesterase activity in the micromolar range.

Among the aromatic plants belonging to the Lamiaceae family, the genus Thymus is noteworthy for the numerous species and varieties of wild-growing plants, some known to have medicinal properties. The present study aimed to evaluate antioxidant and acetylcholinesterase (AChE) inhibitory activities of the ethanolic extracts of six selected Thymus species growing in Croatia (T. longicaulis C. Presl, T. praecox Opiz subsp. polytrichus (A. Kern. ex Borbás)Jalas, T. pulegioides L., T. serpyllum L. subsp. serpyllum, T. striatus Vahl and T. vulgaris L.). Contents of the total polyphenols (10.9-14.9%), tannins (2.7-5.2%) and flavonoids (0.6-1.5%) in the studied extracts were determined spectrophotometrically. Their antioxidant effectiveness was assessed using five different assays, in comparison with reference antioxidants. All tested Thymus extracts possessed DPPH (IC50 3-6 μg/mL) and hydroxyl (IC50 462-721 μg/mL) free radical scavenging activities, strong reducing properties (IC50 11-15 μg/mL), ferrous ion-chelating ability (IC50 124-394 μg/mL) and high total antioxidant capacities (238-294 mg AAE/g). In vitro screening for AChE inhibition showed that the Thymus extracts at concentration of 1000 μg/mL inhibited more then 50% of the enzyme activity. Overall, T. longicaulis was found to be the richest source of natural antioxidants and AChE inhibitors. Considering a very large body of evidence supporting the involvement of oxidative stress in neurodegenerative pathologies as well as the fact that AChE inhibition is up to now the most effective therapeutic approach to dementia, our findings indicated a great potential for novel use of Thymus species in preventing and treating of Alzheimer’s and other aging related diseases.

Alzheimer´s disease (AD) is a degenerative neurological disorder characterized by senile plaques containing amyloid ß protein and loss of cholinergic neuromediators in the brain. The most remarkable biochemical change in AD patients is reduction of acetylcholine (ACh) level in hippocampus and cortex in the brain. Therefore, inhibition of acetylcholinesterase (AChE), the enzyme responsible for hydrolysis of ACh at the cholinergic synapse, is currently the most established approach to treat AD. There are a few synthetic medicines, e.g. tacrine, donepezil, galantamine and the natural based-products rivastigmine and physostigmine for treatment of cognitive dysfunction and memory loss associated with AD. These compounds have been reported to have adverse effects including gastrointestinal disturbances and problems associated with bioavailability, which reinforces the interest in finding better AChE inhibitors from natural resources. Recent studies found that Alzheimer's patients with dementia often have "disturbance in antioxidant balance which may predispose to increased oxidative stress". The aim of this work was to determine antiacetylcholinesterase as well as antioxidant activity of essential oil from Dalmatian endemic black pine needles, Pinus nigra Arnold ssp. dalmatica (Vis.) Franco. Essential oil of Dalmatian endemic black pine needles, Pinus nigra Arnold ssp. dalmatica (Vis.) Franco, has complex chemical composition. Determination of its chemical composition was carried out by means of GC/MS spectrometry. The main components of the oil are α-pinene (24, 3%), β-pinene (16, 0%), germacrene D (14, 6%) and β-caryophyllene (9, 6%). Acetylcholinesterase (AChE) enzyme inhibitory activity was determined using Ellman method. AChE inhibitory activity of Dalmatian black pine essential oil compared with potent AChE inhibitor physostigmine showed relatively good inhibitory effect. Antioxidant activity was evaluated using DPPH and FRAP assays. The results showed weak antioxidant activity in both cases in comparison to commercially used antioxidants (BHT and vitamin C). Low antioxidant activity of Dalmatian black pine essential oil can be ascribed to the lack of compounds containing -OH groups, to which is usually ascribed.

The synthesis of a new series of imidazo[2,1-b]thiazole derivatives is described. They were tested as acetylcholinesterase inhibitors by means of a chemiluminescent method suitable for high throughput screening. The compounds without quaternization had no appreciable inhibitory potency probably because they are poorly soluble in water. The corresponding quaternized compounds were good inhibitors with activity related to the spacer employed.