Anti-acetylcholinesterase Activity Research Articles

Structural Elucidation and Total Synthesis for the Pair of Unprecedented Polypyridines with Anti-AChE and HIV-1 Protease Activities from Alangium chinense.

Unlike reported pyridine hybrids, 2S (1a) and 2R-alanginenmine A (1b) from Alangium chinense featuring an unprecedented piperidine-bridged polypyridine skeleton represented a pair of alkaloid subtypes with a unique multiple pyridine scaffold. Enlightened by the rare structural characteristics and possible biosynthetic pathway, (±)-alanginenmine A (1) have been achieved in ideal yield by gram-class total synthesis with four steps. In addition, both compounds 1a and 1b exhibited anti-acetylcholinesterase (AChE) and HIV-1 protease activities in the biological activity evaluation. Further, molecular docking was investigated for the mechanism of action between the isolated compounds and HIV-1 protease. The stronger Coulomb interactions and van der Waals interaction, as well as the hydrogen bond interactions of 1a, might be the main cause for its better anti-HIV-1 protease activity than 1b. This work provided a comprehensive research including natural product discovery, bioactivity evaluation, and total synthesis for the new type of leading anti-HIV-1 protease.

Anticholinesterase activity of Areca Catechu: In Vitro and in silico green synthesis approach in search for therapeutic agents against Alzheimer's disease.

For many years, the primary focus has been on finding effective treatments for Alzheimer's disease (AD), which has led to the identification of promising therapeutic targets. The necessity for AD stage-dependent optimal settings necessitated a herbal therapy strategy. The plant species Areca Catechu L. (AC) was selected based on the traditional uses against CNS-related diseases. AC leaf extract were prepared using a Soxhlet extraction method and hydroxyapatite nanoparticles (HAp-NPs) were synthesized from the same (AC-HAp-NPs). Powder X-ray diffractometer (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), selected area electron diffraction (SAED) and fourier transform infrared spectroscopy (FTIR) were used to confirm the structure and morphology of the as-prepared AC-HAp-NPs. The crystalline character of the AC-HAp-NPs was visible in the XRD pattern. The synthesized material was found to be nanoflake, with an average diameter of 15-20nm, according to SEM analysis. The TEM and SAED pictures also revealed the form and size of AC-HAp-NPs. In vitro anti-acetylcholinesterase and butyrylcholinesterase (AChE and BChE) activities of hydroxyapatite nanoparticles produced from an AC leaf extract was tested in this study. When compared to control, AC-HAp-NPs had higher anti-AChE and BChE activity. The anti-acetylcholinesterase action of phytoconstituents generated from AC leaf extract was mediated by 4AQD and 4EY7, according to a mechanistic study conducted utilizing in silico research. The global and local descriptors, which are the underpinnings of Conceptual Density Functional Theory (CDFT), have been predicted through the MN12SX/Def2TZVP/H2O model chemistry to help in the comprehension of the chemical reactivity properties of the five ligands considered in this study. The CDFT experiments are supplemented by the calculation of several useful calculated pharmacokinetics indices, their expected biological targets connected to the bioavailability of the five ligands in order to further the goal of studying their bioactivity.

Diverse guaiane-type sesquiterpenoids from the root of Daphne genkwa based on molecular networking

Eleven undescribed guaiane-type sesquiterpenoids, named daphnegenols A-K (1–11) and a known analog (12) were targeted for isolation from the root of Daphne genkwa by LC-MS/MS-based molecular networking. Their diverse structures were elucidated through extensive spectroscopic methods, quantum chemical calculation and X-ray single crystal diffraction, including 5/7 bicycle, 5/6/7 tricycles and 5/6/5 tricycles guaiane-type sesquiterpenoid. Daphnegenol A (1) possessed a rare six membered oxyheterocyclic ring which was constructed by oxidation and cyclization at C-1 and C-11. The anti-acetylcholinesterase and anti-neuroinflammatory activities of compounds 1–12 were measured.

Neuroprotective Effect of Artichoke-Based Nanoformulation in Sporadic Alzheimer's Disease Mouse Model: Focus on Antioxidant, Anti-Inflammatory, and Amyloidogenic Pathways.

The vast socio-economic impact of Alzheimer’s disease (AD) has prompted the search for new neuroprotective agents with good tolerability and safety profile. With its outstanding role as antioxidant and anti-inflammatory, alongside its anti-acetylcholinesterase activity, the artichoke can be implemented in a multi-targeted approach in AD therapy. Moreover, artichoke agricultural wastes can represent according to the current United Nations Sustainable Development goals an opportunity to produce medicinally valuable phenolic-rich extracts. In this context, the UPLC-ESI-MS/MS phytochemical characterization of artichoke bracts extract revealed the presence of mono- and di-caffeoylquinic acids and apigenin, luteolin, and kaempferol O-glycosides with remarkable total phenolics and flavonoids contents. A broad antioxidant spectrum was established in vitro. Artichoke-loaded, chitosan-coated, solid lipid nanoparticles (SLNs) were prepared and characterized for their size, zeta potential, morphology, entrapment efficiency, release, and ex vivo permeation and showed suitable colloidal characteristics, a controlled release profile, and promising ex vivo permeation, indicating possibly better physicochemical and biopharmaceutical parameters than free artichoke extract. The anti-Alzheimer potential of the extract and prepared SLNs was assessed in vivo in streptozotocin-induced sporadic Alzheimer mice. A great improvement in cognitive functions and spatial memory recovery, in addition to a marked reduction of the inflammatory biomarker TNF-α, β-amyloid, and tau protein levels, were observed. Significant neuroprotective efficacy in dentate Gyrus sub-regions was achieved in mice treated with free artichoke extract and to a significantly higher extent with artichoke-loaded SLNs. The results clarify the strong potential of artichoke bracts extract as a botanical anti-AD drug and will contribute to altering the future medicinal outlook of artichoke bracts previously regarded as agro-industrial waste.

Elsholtzia ciliata (Thunb.) Hyland: A Review of Phytochemistry and Pharmacology.

In this paper, the confusion of the sources of medicinal materials was briefly expounded, and the differences among the varieties were pointed out. At the same time, the chemical components and pharmacological properties of Elsholtzia ciliata (Thunb.) Hyland (E. ciliata) were reviewed. The structures of 352 compounds that have been identified are listed. These mainly include flavonoids, terpenoids, phenylpropanoids, alkaloids, and other chemical components. They have antioxidant, anti-inflammatory, antimicrobial, insecticidal, antiviral, hypolipidemic, hypoglycemic, analgesic, antiarrhythmic, antitumor, antiacetylcholinesterase, and immunoregulator activities. At present, there are many researches using essential oil and alcohol extract, and the researches on antioxidant, anti-inflammatory, anti-microbial, and other pharmacological activities are relatively mature. This paper aims to summarize the existing research, update the research progress regarding the phytochemicals and pharmacology of E. ciliate, and to provide convenience for subsequent research.

New carbazol derivatives containing 1,2,4-triazole: Synthesis, characterization, DFT study, acetylcholinesterase activity and docking study

Carbazol derivatives, 4-(((9-ethyl-9H-carbazol-3-yl)methylene)amino)-5-methyl-2,4-dihydro-3H-1,2,4-triazole-3-one (3) and 5-benzyl-4-(((9-ethyl-9H-carbazol-3-yl) methylene) amino)-2,4-dihydro-3H-1,2,4-triazole-3-one (4), were synthesized. Compounds 3 and 4 were characterized by The Fourier transform infrared (FTIR), proton and carbon-13 nuclear magnetic resonance (1H- and 13C- NMR) spectroscopic methods. Density Functional Theory (DFT) calculations for compounds 3 and 4 were performed at B3LYP/6–311++G(d,p) level. Optimized geometry, IR and NMR parameters of compounds 3 and 4 were obtained. The in vitro anti-acetylcholinesterase activity of the compounds were examinated. In addition, Compounds 3 and 4 were tested to determine possible interactions against human acetylcholinesterase by in silico analysis.

Insight into Isolation and Characterization of Phenolic Compounds from Hawthorn (Crataegus pinnatifida Bge.) with Antioxidant, Anti-Acetylcholinesterase, and Neuroprotective Activities.

Recent epidemiologic studies have demonstrated a link between the consumption of daily functional fruits rich in phenols and the prevention of disease for neurodegenerative disorders. Hawthorn products are derived from the functional fruit hawthorn, which is rich in phenols and has been used around the world for centuries. In order to explore the phenolic components in hawthorn, the investigation of the ethanol extract led to the separation of five new phenol compounds (1a/1b, 2-4), including one pair of enantiomers (1a/1b), along with seven disclosed analogs (5-11). Their structures were elucidated based on extensive spectroscopic analyses and electronic circular dichroism (ECD). The compounds (1-11) were tested for antioxidant activities by 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulphonicacid) (ABTS), and ferric reducing antioxidant power (FRAP) methods. Apart from that, monomeric compounds 2, 4, and 6 exhibited more potent protective capabilities against H2O2 (hydrogen peroxide)-induced SH-SY5Y cells. Meanwhile, electronic analyses were performed using the highest occupied molecular orbital (HOMO), and the lowest unoccupied molecular orbital (LUMO) to analyze compounds 2, 4, and 6. Furthermore, compounds (1-11) measured acetylcholinesterase (AChE) inhibitory activities, and 2, 4, and 6 possessed greater AChE inhibitory activity than donepezil. At the same time, molecular docking was used to investigate the possible mechanism of the interaction between active compounds (2, 4, and 6) and AChE.

Novel 3-phenyl-1- (alkylphenyl)-9-oxa-4-azaphenanthren-10-ones as inhibitors of some enzymes: synthesis, characterization, biological evaluation and molecular docking studies

A series of novel 3-phenyl-1-(alkylphenyl)-9-oxa-4-azaphenanthren-10-ones and (E)-1-phenyl-3-(aryl)prop-2-en-1-ones were synthesized and characterized by IR, 1H NMR, 13C spectroscopy and elemental analysis. The synthesized Compounds 5a–f were subjected to molecular docking simulation with three proteins, namely, tyrosyl-tRNA synthetase, heme oxygenase 1 and acetylcholinesterase to evaluate the antibacterial, antioxidant and acetylcholinesterase inhibition, respectively. Moreover, the docked poses of all compounds inside the proteins were subjected to further dynamic simulation through the calculation of the binding free energy using MM-GBSA analysis. Compound 5d exhibits high potential inhibition against antibacterial, antioxidant and acetylcholinesterase activities. Compounds 3d, 3f, 5a and 5d recorded an important scavenging activity in DPPH and ABTS assays. Investigation of the anti-acetylcholinesterase activity of the synthesized compounds showed that Compounds 5a and 3d are the most potent inhibitors against AchE, with percent inhibition values of 38 and 30%, respectively. Communicated by Ramaswamy H. Sarma

Investigations of specialised metabolites of endophyte Diaporthe destruens hosted in Illigera orbiculata C. Y. Wu

A chemical investigation of the endophytic fungus Diaporthe destruens from the Hernandiaceae plant Illigera orbiculata C. Y. Wu collected from southern Yunnan Province, China, led to the isolation of six undescribed compounds, including two azaphilone analogs, which are a pair of epimers (13R-hydroxy-chermesinone A and 13S-hydroxy-chermesinone A); a pyrrole derivative (1-(4-(methoxymethyl)-1H-pyrrol-3-yl)ethan-1-one); an isoindolone derivative (4-hydroxy-6-methoxyisoindolin-1-one); a benzylbenzene derivative (destruensine A) and a conjectural fragment of polyketide ((2R,4R)-2-(methoxymethyl)pentane-1,4-diol) along with nine known compounds. Their structures were elucidated by spectroscopic methods and HRESIMS, and the absolute configurations were further confirmed by electronic circular dichroism (ECD) and chemical derivatization. The antimicrobial activities, anti-acetylcholinesterase activities, antiproliferation, and NO production inhibitory effects of compounds 1–15 were evaluated.

Two New Picoline-Derived Meroterpenoids with Anti-Acetylcholinesterase Activity from Ascidian-Derived Fungus Amphichorda felina.

Amphichoterpenoids D (1) and E (2), two new picoline-derived meroterpenoids with a rare 6/6/6 tricyclic pyrano[3,2-c]pyridinyl-γ-pyranone scaffold, were isolated from the ascidian-derived fungus Amphichorda felina SYSU-MS7908. Their structures, including the absolute configurations, were established by extensive spectroscopic methods (1D and 2D NMR and high-resolution mass spectrometry) and ECD calculations. Compounds 1 and 2 showed anti-acetylcholinesterase (anti-AChE) activities with IC50 values of 12.5 μM and 11.6 μM, respectively. The binding interactions between 1, 2, and AChE were investigated using molecular docking analyses.

Which Extraction Solvents and Methods Are More Effective in Terms of Chemical Composition and Biological Activity of Alceafasciculiflora from Turkey?

The bioactive content, antioxidant properties, and enzyme inhibition properties of extracts of Alcea fasciculiflora from Turkey prepared with different solvents (water, methanol, ethyl acetate) and extraction methods (maceration, soxhlet, homogenizer assisted extraction, and ultrasound assisted extraction) were examined in this study. UHPLC-HRMS analysis detected or annotated a total of 50 compounds in A. fasciculiflora extracts, including 18 hydroxybenzoic and hydroxycinnamic acids, 7 Hexaric acids, 7 Coumarins, 15 Flavonoids, and 3 hydroxycinnamic acid amides. The extracts had phenolic and flavonoid levels ranging from 14.25 to 24.87 mg GAE/g and 1.68 to 25.26 mg RE/g, respectively, in the analysis. Both DPPH and ABTS tests revealed radical scavenging capabilities (between 2.63 and 35.33 mg TE/g and between 13.46 and 76.27 mg TE/g, respectively). The extracts had reducing properties (CUPRAC: 40.38–78 TE/g and FRAP: 17.51–42.58 TE/g). The extracts showed metal chelating activity (18.28–46.71 mg EDTAE/g) as well as total antioxidant capacity (phosphomolybdenum test) (0.90–2.12 mmol TE/g). DPPH, ABTS, FRAP, and metal chelating tests indicated the water extracts to be the best antioxidants, while the ethyl acetate extracts had the highest overall antioxidant capacity regardless of the extraction technique. Furthermore, anti-acetylcholinesterase activity was identified in all extracts (0.17–2.80 mg GALAE/g). The water extracts and the ultrasound-assisted ethyl acetate extract were inert against butyrylcholinesterase, but the other extracts showed anti-butyrylcholinesterase activity (1.17–5.80 mg GALAE/g). Tyrosine inhibitory action was identified in all extracts (1.79–58.93 mg KAE/g), with the most effective methanolic extracts. Only the ethyl acetate and methanolic extracts produced by maceration and homogenizer aided extraction showed glucosidase inhibition (0.11–1.11 mmol ACAE/g). These findings showed the overall bioactivity of the different extracts of A. fasciculiflora and provided an overview of the combination of solvent type and extraction method that could yield bioactive profile and pharmacological properties of interest and hence, could be a useful reference for future studies on this species.

Identification of potential anti‐Alzheimer agents from Pistacia atlantica Desf. galls using UPLC fingerprinting, chemometrics, and molecular docking analyses

The purpose of this study was to test extracts from P. atlantica Desf. galls (PAG) for anti-acetylcholinesterase (AChE) and anti-butyrylcholinesterase (BuChE) activity, and investigate the influence of harvesting time, plant gender, and growing location on such activity. The IC50 values of PAG extracts ranged from 56.42-68.94 μg/ml to 82.43-95.81 μg/ml, respectively. Our findings revealed that the anti-AChE/BuChE activity of PAG extracts was relatively more influenced by the time of harvest than by plant gender and growing location. A combination of UPLC fingerprinting and chemometrics using partial least squares regression analysis identified the presence of two phenolic compounds, namely methyl gallate and digalloylquinic, as responsible for the anti-AChE/BuChE activity of PAG extracts. A molecular docking study further confirmed that both compounds were able to bind to AChE and BuChE and interact with key residues of the active sites of these enzymes. Practical applications Pistacia atlantica Desf. is an important medicinal plant whose galls are traditionally used in many Mediterranean countries for the treatment of Alzheimer’s disease. The combination of fingerprint technology with chemometrical approaches in this study enabled the putative identification of metabolites in P. atlantica gall extracts responsible for anticholinesterase activity. This investigation highlights the potential of P. atlantica galls as a promising source for the discovery and development of new anti-Alzheimer agents.

Access to new phosphonate- and imidazolidine-benzopyrimidinone derivatives as antityrosinase and anti-acetylcholinesterase agents: Design, synthesis and molecular docking

To discover new acetylcholinesterase and tyrosinase inhibitors, a series of dialkyl phosphonate-benzopyrimidinones 4a-b was prepared via Michaelis-Arbuzov rearrangement (Arbusov reaction) of benzopyrimidinone chloride 2 with trialkyl phosphate, as well as a series of imidazolidine-benzopyrimidinone derivatives 5a-g synthesized by Mannich reaction of 2-((arylamino)methyl) benzopyrimidin-4(3H)-one 3 with formaldehyde. The structures of the new target compounds were investigated by 1H NMR, 13C NMR and ESI-HRMS. All synthesized compounds were evaluated for their anti-acetylcholinesterase and antityrosinase activities. Compounds 5f, 3g and 4b showed the highest tyrosinase inhibition and compounds 3g, 3d and 5g were found to be the most anti-acetylcholinesterase agents. Moreover, structure activity relationship (SAR) was discussed for all synthesized compounds and the interaction modes of the most potent inhibitors were confirmed through molecular docking studies.

Laurel essential oil: biological activities and application for semolina preservation against the red flour beetle Tribolium castaneum (Tenebrionidae)

ABSTRACT The phytochemical composition of Laurus nobilis essential oil and their anticholinesterase, antioxidant, and insecticidal potential were studied. Also, the oil volatile fraction was compared in semolina at the beginning and after storage periods. For that, a headspace solid-phase-microextraction analysis (HS-SPME) coupled with gas chromatography and mass spectrometry was undertaken. Significant quantitative and qualitative differences of the oil volatile fraction were detected according to storage periods and occupation space ratios. Additionally, anti-acetylcholinesterase activity of L. nobilis oil against T. castaneum adults was evaluated. Results revealed that insecticide activity varied according to storage duration and occupation space. Besides, the oil acts on acetylcholine hydrolysis by inhibiting the activity of acetylcholinesterase. These results highlighted that L. nobilis essential oil may be recommended as an eco-friendly alternative for preserving semolina during storage.

Bioactive Components from Ampelopsis japonica with Antioxidant, Anti-α-Glucosidase, and Antiacetylcholinesterase Activities

The dried root of Ampelopsis japonica (Thunb.) Makino (A. japonica.) is a traditional medicine used to treat fever, pain, and wound healing. It exhibits anti-inflammatory, antitumor, antityrosinase, and antimelanogenic activities. In this paper, we used different solvent extracts from the root of A. japonica to determine their antioxidant activity. Acetone extract showed relatively strong antioxidant properties by 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), 2,2-diphenyl-1-(2,4,6-trinitrophenyl)hydrazyl (DPPH), superoxide radical scavenging activity, and ferric reducing antioxidant power (FRAP) assays. In addition, these extracts also showed significant α-glucosidase and acetylcholinesterase (AChE) inhibitory activities. Acetone extract significantly inhibited α-glucosidase with an IC50 value of 8.30 ± 0.78 μg/mL, and ethanol extract remarkably inhibited AChE with an IC50 value of 37.08 ± 7.67 μg/mL. Using HPLC analysis and comparison with the chemical composition of various solvent extracts, we isolated seven active compounds and assessed their antioxidant, anti-α-glucosidase, and anti-AChE activities. Catechin (1), gallic acid (2), kaempferol (3), quercetin (4), resveratrol (6), and epicatechin (7) were the main antioxidant components in the root of A. japonica. According to the results of DPPH, ABTS, and superoxide radical scavenging assays, these isolates showed stronger antioxidant capacity than butylated hydroxytoluene (BHT). Moreover, 1, 3, 4, euscaphic acid (5), 6, and 7 also expressed stronger anti-α-glucosidase activity than the positive control acarbose, and all the isolated compounds had a good inhibitory effect on AChE. Molecular docking models and hydrophilic interactive modes for AChE assays suggest that 1 and 5 exhibit unique anti-AChE potency. This study indicates that A. japonica and its active extracts and components may be a promising source of natural antioxidants, α-glucosidase, and AChE inhibitors.

FLAVONOIDS AND LIGNANS FROM THE LEAVES OF NEPETA MULTIFIDA (LAMIACEAE) AND THEIR BIOAC-TIVITY

A perennial plant Nepeta multifida L. (syn. Schizonepeta multifida (L.) Briq.) is one of the most common species of the Lamiaceae family growing in Eastern Siberia and used in traditional oriental medicine. The chemical composition of N. multifida has not been sufficiently studied. Chromatographic separation of phenolic compounds of N. multifida leaves using column chromatography and preparative HPLC resulted in the isolation of sixteen compounds, including a new flavonoid identified as luteolin-7-O-(3′′,6′′-di-O-acetyl)-β-D-glucopyranoside. Known compounds were O-glycosides of luteolin and apigenin, rosmarinic acid, salvianolic acids A and B, and schizotenuin A. Quantitative analysis of N. multifida leaves by HPLC-UV assay showed the high content of rosmarinic acid (8.36–35.71 mg/g), luteolin-7-O-glucuronide (2.03–14.18 mg/g) and schizotenuin A (5.29–9.56 mg/g). The highest level of phenolic compounds was found in the flowering and fruiting phases. Using Ellman’s spectrophotometric method, it was found that N. multifida leaf extract and some compounds had antiacetylcholinesterase activity, and luteolin glycosides being the most active showed the level of concentration of half-maximal enzyme inhibition (IC50) 29.03–58.36 μg/mL. Thus, as a result of the present study, it was found that the leaves of N. multifida contain various groups of phenolic compounds capable of inhibiting the activity of acetylcholinesterase.

Molecular engineering and activity improvement of acetylcholinesterase inhibitors: Insights from 3D-QSAR, docking, and molecular dynamics simulation studies

The carbamate molecule rivastigmine was found to possess promising anti-acetylcholinesterase activity, enabling to target and occupy choline binding sites, and as a result, widely used to improve the treatment of Alzheimer's disease (AD). Higher dose of rivastigmine indicates rapid onset but more adverse effects, such as the large fluctuations in plasma concentration level and frequent incidence of gastrointestinal side effect. To solve the dilemma, we developed a three-dimensional quantitative structure-activity relationship (3D-QSAR), docking and molecular dynamics (MD) simulation strategy to construct a dismountable nanoplatform of inhibitor engineering, verification and application for improving the inhibitory activity per unit concentration. With the aid of 3D-QSAR method, we constructed a model by using 25 molecules reported, and verified well the rationality of these QSAR models by non-cross validation coefficient (r2 = 0.902). Docking and MD results show that rivastigmine, as a control, does target exactly the binding sites of acetylcholinesterase, those already observed experimentally, in turn, confirming the reliability of the present 3D-QSAR results. The method suggests that groups with electron-donating chemical property can improve the inhibitory activity, and screens out two novel inhibitors L-1 and L-2 with more activity from database (about 8000 compounds). Moreover, L-1 and L-2 not only target exactly the same binding sites of acetylcholinesterase as the rivastigmine does, but also hold stronger binding energy, showing a more powerful inhibitory ability. More broadly, this work showcases an approach in the engineering of carbamate inhibitors to enhance their inhibitory activity using electron-donating groups, which simplifies the design process of complex bioactive molecules.

Metabolites Profiling of Manilkara mabokeensis Aubrév Bark and Investigation of Biological Activities.

Manilkara mabokeensis Aubrév is a tree that belongs to the Sapotaceae family, native to the tropical forest in Latin America, Asia, Australia, and Africa. The bark of this species is used as traditional medicine to treat diseases. The present study is the first phytochemical investigation on M. mabokeensis Aubrév bark in terms of phytochemical composition and bioactivity. Among the different extracts, ethyl acetate (EtOAc) exhibited the highest values of total phenolic content (TPC), total flavonoid content (TFC), condensed tannin content (CTC), and reducing sugar content, as well as a high antioxidant activity. Interestingly, gas chromatography-flame ionization detector (GC-FID) and gas chromatography-mass spectrometry (GC-MS) analysis were enabled to identify 23 compounds in the essential oil of M. mabokeensis Aubrév bark, which have not been previously described in the literature. Phytol and 8,14-cedranoxide were the major identified compounds, with area percentages of 27.9 and 18.8%, respectively. For HPLC analysis, 3,4-dihydroxy-benzoic acid methyl ester showed the highest concentration with 61.8 mg/g of dry residue (dr) among other identified molecules. Manilkara mabokeensis Aubrév bark MeOH extract showed a good anti-15-lipoxygenase (anti-15-LOX) and anti-acetylcholinesterase (anti-AChE) activities of 65.8 and 71.0%, respectively, while it exhibited a moderate antixanthine oxidase (anti-XOD) activity (41.5%) at 50 μg/mL. Furthermore, cyclohexane (CYHA) and ethyl acetate induced the highest cytotoxicity against the human ovarian cancer cell lines, OVCAR (49.5%) and IGROV (48.7%), respectively. Taken together, obtained results argue that M. mabokeensis Aubrév bark is an excellent source of natural compounds and justify its use in folk medicine.

Chemical composition, antibiofilm, cytotoxic, and anti-acetylcholinesterase activities of Myrtus communis L. leaves essential oil

BackgroundThe potential of essential oils (EOs) and of their principal constituents for eradication of biofilm and at the same time the research of new potential acetylcholinesterase inhibitors is gaining increasing interest in last years. The aims of this study were to determine the chemical composition and to evaluate the antibacterial, cytotoxic, and anti-acetylcholinesterase properties of Myrtus communis leaves essential oil and its main constituents.MethodsEssential oil was obtained by hydrodistillation of M. communis L. leaves and was analyzed by GC and GC–MS. The antimicrobial activity was carried out against both gram-negative and gram-positive bacteria. The microdilution method was used to estimate the minimum inhibitory concentrations (MICs). Then, the capacity of essential oil and its main constituent to inhibit biofilm growth, with the method of O’Toole and Kolterand, and the metabolic activity of biofilm cells through the MTT colorimetric method were evaluated at different times. Moreover, was studied the potential cytotoxic activity against SH-SY5Y cell line with MTT assay and the anti-acetylcholinesterase activity using Ellman’s assay.ResultsMyrtenyl-acetate, 1,8 cineole, α-pinene, and linalool were the main components in the EO. The myrtle EO, at the minimum tested dose (0.4 mg/ml), inhibited S. aureus biofilm by 42.1% and was capable of inhibiting the biofilm cell metabolism in all tested strains, except Staphylococcus aureus. Moreover, the EO showed good cytotoxic and anti-acetylcholinesterase activities IC50 of 209.1 and 32.8 μg/ml, respectively.ConclusionsThe results suggest that myrtle EO and its main constituents could be used as possible products that could act against the resistant pathogenic species E. coli, P. aeruginosa, L. monocytogenes and S. aureus, on the other hand, as possible coadjutants in the treatment of neurological diseases.

Novel and Potent Acetylcholinesterase Inhibitors for the Treatment of Alzheimer's Disease from Natural (±)-7,8-Dihydroxy-3-methyl-isochroman-4-one.

Alzheimer’s disease (AD) is a neurodegenerative disease that causes memory and cognitive decline as well as behavioral problems. It is a progressive and well recognized complex disease; therefore, it is very urgent to develop novel and effective anti-AD drugs. In this study, a series of novel isochroman-4-one derivatives from natural (±)-7,8-dihydroxy-3-methyl-isochroman-4-one [(±)-XJP] were designed and synthesized, and their anti-AD potential was evaluated. Among them, compound 10a [(Z)-3-acetyl-1-benzyl-4-((6,7-dimethoxy-4-oxoisochroman-3-ylidene)methyl)pyridin-1-ium bromide] possessed potent anti-acetylcholinesterase (AChE) activity as well as modest antioxidant activity. Further molecular modeling and kinetic investigations revealed that compound 10a was a dual-binding inhibitor that binds to both catalytic anionic site (CAS) and peripheral anionic site (PAS) of the enzyme AChE. In addition, compound 10a exhibited low cytotoxicity and moderate anti-Aβ aggregation efficacy. Moreover, the in silico screening suggested that these compounds could pass across the blood–brain barrier with high penetration. These findings show that compound 10a was a promising lead from a natural product with potent AChE inhibitory activity and deserves to be further developed for the prevention and treatment of AD.