Flavonoids are naturally occurring polyphenolic compounds known for their extensive range of biological activities. This review focuses on the inhibitory effects of flavonoids on acetylcholinesterase (AChE) and their potential as therapeutic agents for cognitive dysfunction. AChE, a serine hydrolase that plays a crucial role in cholinergic neurotransmission, is a key target in the treatment of cognitive impairments due to its function in acetylcholine hydrolysis. Natural polyphenolic compounds, particularly flavonoids, have demonstrated significant inhibition of AChE, positioning them as promising alternatives or adjuncts in neuropharmacology. This study specifically examines flavonoids such as quercetin, apigenin, kaempferol, and naringenin, investigating their inhibitory efficacy, binding mechanisms, and additional neuroprotective properties, including their antioxidant and anti-inflammatory effects. In vitro, in vivo, and in silico analyses reveal that these flavonoids effectively interact with both the active and peripheral anionic sites of AChE, resulting in increased acetylcholine levels and the stabilization of cholinergic signaling. Their mechanisms of action extend beyond mere enzymatic inhibition, as they also exhibit antioxidant and anti-amyloidogenic properties, thereby offering a multifaceted approach to neuroprotection. Given these findings, flavonoids hold considerable therapeutic potential as modulators of AChE, with implications for enhancing cognitive function and treating neurodegenerative diseases. Future studies should prioritize the enhancement of flavonoid bioavailability, evaluate their efficacy in clinical settings, and explore their potential synergistic effects when combined with established therapies to fully harness their potential as neurotherapeutic agents.
Acetylcholinesterase (AChE) has emerged not only as a cholinergic enzyme but also as a modulator of β-amyloid (Aβ) aggregation via its peripheral anionic site (PAS), making it a dual-purpose target in Alzheimer’s disease. While classical AChE inhibitors provide symptomatic relief, they lack efficacy against the amyloidogenic cascade. This review highlights recent advances in multifunctional AChE pharmacophores that inhibit enzymatic activity while simultaneously interfering with Aβ aggregation, oxidative stress, metal dyshomeostasis, and neuroinflammation. Particular emphasis is placed on dual-site inhibitors targeting both catalytic and peripheral domains, multi-target-directed ligands (MTDLs) acting on multiple neurodegenerative pathways, and metal-chelating hybrids that address redox-active metal ions promoting Aβ fibrillization. We also discuss enabling technologies such as AI-assisted drug design, high-resolution structural tools, and human induced pluripotent stem cell (iPSC)-derived neuronal models that support physiologically relevant validation. These insights reflect a paradigm shift towards disease-modifying therapies that bridge molecular pharmacology and pathophysiological relevance.
Ochratoxin A (OTA) is considered as the most toxic of the other ochratoxins synthesized by various fungal species belonging to the Aspergillus and Penicillium families. OTA commonly contaminates food and beverages, resulting in animal and human health issues. The toxicity of OTA is known to cause liver damage and is still being researched. However, current findings do not provide clear insights into the toxin mechanism of action. The current studies focusing on the use of potentially protective compounds against the effects of the toxin are insufficient as they are mainly conducted on animals. Further research is required to fill the existing gaps in both fields (namely the exact OTA molecular mechanism and the prevention of its toxicity in the human liver). This review article is a summary of the so far obtained results of studies focusing on the OTA hepatotoxicity, its mode of action, and the known approaches of liver cells protection, which may be the base for expanding other research in near future.
Over 20 laterally substituted, mainly by fluorine and other more bulky substituents like chlorine and methyl group, 4,4′′′-dialkyl-p-quaterphenyls have been synthesised and mesomorphic properties, phase transition temperatures and enthalpies were measured. The influence of the number of lateral substituents and their type along with their position in the molecular core have been analysed and compared with similarly substituted terphenyl analogues. The example of the eutectic mixture composed of synthesised quaterphenyl derivatives has been formulated and characterised.
Syntheses, mesogenic and dielectric properties of three-ring alkylcyclohexyl, alkoxy and alkylphenyl benzoates substituted with four fluorine atoms or with two fluorine atoms and simultaneously a cyano group or two cyano groups are described. Their properties are compared with analogous three-ring phenyl tolanes. Conformation analysis and the calculation of dipole moments with the quantum chemistry method are performed to explain the experimental results. Several four fluorine-substituted two-ring tolanes and biphenyls are also prepared, which are used as a solvent decreasing viscosity, melting point and clearing point of the formulated mixtures. Examples of mixtures prepared from the esters and tolanes with high dielectric anisotropy are given. Curiosity is observed that 4ʹ-(4-ethoxyphenyl)-4-pentyloxy-2,2ʹ,3,3ʹ-tetrafluorotolane is not the mesogenic compound, while analogous ester 4ʹ-ethoxy-2,3-difluorobiphenyl-4-yl 2,3-difluoro-4-pentyloxybenzoate exhibits a broad temperature range of the nematic phase. Graphical Abstract