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Aurantiochytrium is a heterotrophic marine microalga that has potential industrial applications. The main objectives of this study were to isolate an Aurantiochytrium strain from Sand Cay (Son Ca) Island, Vietnam, optimize its culture conditions, determine its nutritional composition, extract polyunsaturated fatty acids (PUFAs) in the free (FFA) and the alkyl ester (FAAE) forms, and evaluate the antioxidation and neuroprotection properties of the PUFAs. Aurantiochytrium sp. SC145 can be grown stably under laboratory conditions. Its culture conditions were optimized for a dry cell weight (DCW) of 31.18 g/L, with total lipids comprising 25.29%, proteins 7.93%, carbohydrates 15.21%, and carotenoid at 143.67 µg/L of DCW. The FAAEs and FFAs extracted from Aurantiochytrium sp. SC145 were rich in omega 3–6–9 fatty acids (40.73% and 44.00% of total fatty acids, respectively). No acute or subchronic oral toxicity was determined in mice fed with the PUFAs in FFA or FAAE forms at different doses over 90 days. Furthermore, the PUFAs in the FFA or FAAE forms and their main constituents of EPA, DHA, and ALA showed antioxidant and AChE inhibitory properties and neuroprotective activities against damage caused by H2O2- and amyloid-ß protein fragment 25–35 (Aβ25-35)-induced C6 cells. These data suggest that PUFAs extracted from Aurantiochytrium sp. SC145 may be a potential therapeutic target for the treatment of neurodegenerative disorders.

A series of novel dimethoxyindanone embedded spiropyrrolidines were synthesized in ionic liquid, [bmim]Br and were evaluated for their inhibitory activities towards cholinesterases. Among the spiropyrrolidines, compound 4f exhibited the most potent activity with an IC50 value of 1.57 µM against acethylcholinesterase (AChE). Molecular docking simulation for the most active compound was employed with the aim of disclosing its binding mechanism to the active site of AChE receptor.

Alzheimer's disease (AD) involves β‐amyloid plaques and tau hyperphosphorylation, driven by oxidative stress and neuroinflammation. Cyclooxygenase‐2 (COX‐2) and acetylcholinesterase (AChE) activities exacerbate AD pathology. Olive leaf (OL) extracts, rich in bioactive compounds, offer potential therapeutic benefits. This study aimed to assess the anti‐inflammatory, anti‐cholinergic, and antioxidant effects of three OL extracts (low, mid, and high bioactive content) in vitro and their protective effects against AD‐related proteinopathies in Caenorhabditis elegans models. OL extracts were characterized for phenolic composition, AChE and COX‐2 inhibition, as well as antioxidant capacity. Their effects on intracellular and mitochondrial reactive oxygen species (ROS) were tested in C. elegans models expressing human Aβ and tau proteins. Gene expression analyses examined transcription factors (DAF‐16, skinhead [SKN]‐1) and their targets (superoxide dismutase [SOD]‐2, SOD‐3, GST‐4, and heat shock protein [HSP]‐16.2). High‐OL extract demonstrated superior AChE and COX‐2 inhibition and antioxidant capacity. Low‐ and high‐OL extracts reduced Aβ aggregation, ROS levels, and proteotoxicity via SKN‐1/NRF‐2 and DAF‐16/FOXO pathways, whereas mid‐OL showed moderate effects through proteostasis modulation. In tau models, low‐ and high‐OL extracts mitigated mitochondrial ROS levels via SOD‐2 but had limited effects on intracellular ROS levels. High‐OL extract also increased GST‐4 levels, whereas low and mid extracts enhanced GST‐4 levels. OL extracts protect against AD‐related proteinopathies by modulating oxidative stress, inflammation, and proteostasis. High‐OL extract showed the most promise for nutraceutical development due to its robust phenolic profile and activation of key antioxidant pathways. Further research is needed to confirm long‐term efficacy. Olive leaf (OL) extracts were assessed for biomedical and phytochemical profiles. High‐OL extract was the most effective in inhibiting AChE, COX‐2, and iron‐reducing activity. Low‐ and high‐OL extracts showed significant effects against Aβ and tau toxicity in vivo. All extracts modulated redox biology at different levels. Only high‐OL extract prevented mitochondrial ROS accumulation.

The present study investigated the synthesis of mesoporous hollow carbon spheres (MHCS) and magnetic mesoporous hollow carbon spheres with core-shell structures (Fe3O4@MHCS). Two acetylcholinesterase sensors (acetylcholinesterase/mesoporous hollow carbon spheres/glassy carbon electrode (AChE/MHCS/GCE) and acetylcholinesterase/core-shell magnetic mesoporous hollow carbon spheres/glassy carbon electrode (AChE/Fe3O4@MHCS/GCE) based on mesoporous carbon materials were prepared. Under the optimum conditions, using Malathion as the model compound, the developed biosensors showed a wide detection range, low detection limit, good reproducibility, and high stability. The AChE/MHCS/GCE electrochemical sensor response exhibited two good linear ranges at the incubation time of 10 min at the Malathion concentration ranges of 0.01 to 100 ppb and 100 to 600 ppb, with a detection limit of 0.0148 ppb (S/N = 3). The AChE/Fe3O4@MHCS/GCE electrochemical sensor that was operated with an incubation time of 12 min at the malathion concentration ranges between 0.01–50 ppb and 50–600 ppb had a detection limit of 0.0182 ppb (S/N = 3). Moreover, the AChE/MHCS/GCE and AChE/Fe3O4@MHCS/GCE biosensors were effective for the detection of real samples, and were demonstrated to be suitable for the field-testing of organophosphorus pesticide (OP) residues.

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.

Little is known about the non-neuronal spermic cholinergic system, which may regulate sperm motility and the acrosome reaction initiation process. We investigated the presence of the key acetylcholine (ACh)-biosynthesizing enzyme, choline acetyltransferase (ChAT), and the acetylcholine-degrading enzymes, acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) and two ACh-receptors in human spermatozoa and seminal plasma. Fresh ejaculates were used for intra- and extracellular flow cytometric analysis of ChAT, AChE, BChE, and alpha-7-nicotinic and M1-muscarinic ACh-receptors in sperm. For determining the source of soluble enzymes, frozen seminal samples (n = 74) were selected on two bases: (1) from vasectomized (n = 37) and non-vasectomized (n = 37) subjects and (2) based on levels of alpha-glucosidase, fructose, or zinc to define sample subgroups with high or low fluid contribution from the epididymis and seminal vesicle, and prostate, respectively. Flow cytometric analyses revealed that ChAT was expressed intracellularly in essentially all spermatozoa. ChAT was also present in a readily membrane-detachable form at the extracellular membrane of at least 18% of the spermatozoa. These were also highly positive for intra- and extracellular BChE (>83%) and M1 (>84%) and α7 (>59%) ACh-receptors. Intriguingly, the sperm was negative for AChE. Analyses of seminal plasma revealed that spermatozoa and epididymides were major sources of soluble ChAT and BChE, whereas soluble AChE most likely originated from epididymides and seminal vesicles. Prostate had relatively minor contribution to the pool of the soluble enzymes in the seminal fluid. In conclusion, human spermatozoa exhibited a cholinergic phenotype and were one of the major sources of soluble ChAT and BChE in ejaculate. We also provide the first evidence for ChAT as an extracellularly membrane-anchored protein. Summary Sentence Human spermatozoa exhibit a predominantly cholinergic phenotype and are the main source of the soluble ChAT and BChE in seminal fluid.

Mosquito-borne diseases remain a significant global public health challenge. This challenge is further exacerbated by the growing resistance of disease-vector species such as Culex pipiens to conventional insecticides. In this study, we present the design, synthesis, and biological assessment of a new series of thiophene-isoquinolinone hybrids as potential larvicides. Among the synthesized compounds, derivatives 5f, 6, and 7 showed significant larvicidal effectiveness against Culex pipiens larvae, with LC₅₀ values of 0.3, 0.1, and 1.85 µg/mL, respectively. Notably, all twelve thiophene-isoquinolinone derivatives were much more toxic than the reference organophosphate insecticide chlorpyrifos (LC₅₀ = 293.8 µg/mL), demonstrating the strength of these chemical structures. Interestingly, the synthetic intermediate compound 1a, a thiophene-based half-ester, exhibited the highest activity (LC₅₀ = 0.004 µg/mL), outperforming all final derivatives despite not being fully optimized. Mechanistic bioassays showed consistent neurotoxic symptoms that suggest a disruption of cholinergic function. Molecular docking and molecular dynamics simulations supported this observation, revealing strong and specific interactions with both acetylcholinesterase (AChE) and nicotinic acetylcholine receptors (nAChRs), which points to a possible dual-target mechanism. Density Functional Theory (DFT) calculations further confirmed the favorable electronic properties and reactivity of the active compounds. The structural variety within this series, along with consistently high potency, may lower the risk of cross-resistance and aid resistance management strategies through compound rotation or combination. Overall, these findings highlight thiophene-isoquinolinone hybrids as a promising option for developing next-generation larvicides that target neurophysiological pathways in insect vectors.

Extensive research has been dedicated to develop compounds that can target multiple aspects of Alzheimer’s disease (AD) treatment due to a growing understanding of AD’s complex multifaceted nature and various interconnected pathological pathways. In the present study, a series of biological assays were performed to evaluate the potential of the tryptamine analogues synthesized earlier in our lab as multi-target-directed ligands (MTDLs) for AD. To assess the inhibitory effects of the compounds, various in vitro assays were employed. Three compounds, SR42, SR25, and SR10, displayed significant AChE inhibitory activity, with IC50 values of 0.70 µM, 0.17 µM, and 1.00 µM, respectively. These values superseded the standard drug donepezil (1.96 µM). In the MAO-B inhibition assay, SR42 (IC50 = 43.21 µM) demonstrated superior inhibitory effects as compared to tryptamine and other derivatives. Moreover, SR22 (84.08%), SR24 (79.30%), and SR42 (75.16%) exhibited notable percent inhibition against the COX-2 enzyme at a tested concentration of 100 µM. To gain insights into their binding mode and to validate the biological results, molecular docking studies were conducted. Overall, the results suggest that SR42, a 4,5 nitro-benzoyl derivative of tryptamine, exhibited significant potential as a MTDL and warrants further investigation for the development of anti-Alzheimer agents.

An important field of research in medicinal and organic chemistry involves halogen-containing heterocyclic synthones, which form the backbone of more complex organic compounds. This study aimed to design and synthesize 28 novel derivatives of 7-aryl-2,3-dihydropyrrolo[2,1-b]quinazolin-9(1H)-one. The derivatives were created from 7-bromoquinoline intermediates to evaluate their potential as cholinesterase inhibitors for treating neurodegenerative diseases such as Alzheimer’s disease. The conditions for the Suzuki–Miyaura cross-coupling reaction were optimized to improve yield and purity. The derivatives were evaluated for their anticholinesterase activity using Ellman’s method, revealing that it most effectively inhibited cholinesterase within the micromolar range. 7-(3-Chloro-4-fluorophenyl)-2,3-dihydropyrrolo[2,1-b]quinazolin-9(1H)-one derivative exhibited the highest inhibitory potency, with an IC50 value of 6.084 ± 0.26 μM. Additionally, molecular dynamics simulations provided insight into how this lead compound interacts with the enzyme, suggesting its potential as a drug candidate for Alzheimer’s disease.

Acetylcholinesterase (AChE) is one of the classical targets in the treatment of Alzheimer’s disease (AD). Inhibition of AChE slows down the hydrolysis of acetycholine and increases choline levels, improving the cognitive function. The achieved success of plant-based natural drugs acting as AChE inhibitors, such as galantamine (GAL) from Galanthus genus and huperzine A from Huperzia serrate (approved drug in China), in the treatment of AD, and the fact that natural compounds (NCs) are considered as safer and less toxic compared to synthetic drugs, led us to screen the available NCs (almost 150,000) in the ZINC12 database for AChE inhibitory activity. The compounds were screened virtually by molecular docking, filtered for suitable ADME properties, and 32 ligands from 23 structural groups were selected. The stability of the complexes was estimated via 1 μs molecular dynamics simulation. Ten compounds formed stable complexes with the enzyme and had a vendor and a reasonable price per mg. They were tested for AChE inhibitory and antioxidant activity. Five compounds showed weak AChE inhibition and three of them exhibited high antioxidant activity.