Anti-acetylcholinesterase Activity Research Articles

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.

Acaricidal, Larvacidal, and Repellent Activity of Elettaria cardamomum Essential Oil against Hyalomma anatolicum Ticks Infesting Saudi Arabian Cattle.

Background: In this experimental study, we aimed to assess the acaricidal effects of Elettaria cardamomum L. essential oil (ECEO) against Hyalomma anatolicum tick in cattle from Saudi Arabia. Methods: Gas chromatography-mass spectrometry (GC-MS) was performed to identify the chemical composition of ECEO. The acaricidal, larvicidal, and repellent activity of ECEO against H. anatolicum was studied through the adult immersion test (AIT), the larval packet test (LPT), the vertical movement behavior of tick’s larvae technique, anti-acetylcholinesterase (AChE) activity, and oxidative enzyme activity. Results: By GC/MS, the most compounds were 1,8-cineole (34.3%), α-terpinyl acetate (23.3%), and α-pinene (17.7%), respectively. ECEO significantly (p < 0.001) increased the mortality rate as a dose-dependent response. After ECEO Treatment, number of eggs, egg weight, and hatchability significantly declined as a dose-dependent response. ECEO at concentrations of 5 µL/mL and above completely killed the larva. The LC50 and LC90 values for ECEO were 1.46 and 2.68 µL/mL, respectively. ECEO at concentrations of 10, 20, and 40 µL/mL showed 100% repellency activity up to 60, 120, and 360 min incubation, respectively. ECEO, especially at ½ LC50 and LC50, significantly inhibited GST and AChE activities of H. anatolicum larvae compared to the control group. Conclusions: We found promising adulticidal, larvicidal, and repellent effects of ECEO against H. anatolicum as a vector of theileriosis in Saudi Arabia. We also found that ECEO displayed these activities through inhibiting AChE and GST. Nevertheless, additional investigations are required to confirm the accurate mechanisms and the relevance of ECEO in practical application.

In Vitro and In Silico Anti-Acetylcholinesterase Activity from Macaranga tanarius and Syzygium jambos.

Macaranga tanarius (MT) and Syzygium jambos (SJ) are pharmacologically reported to have anti-oxidant, anti-inflammatory, and anti-diabetic effects, and can be neuroprotective agents. Our previous work revealed that MT and SJ exhibited 76.32% and 93.81% inhibition against acetylcholinesterase (AChE) at 50 μg/mL final concentration in their ethyl acetate and hexane fractions, respectively. This study was aimed to investigate the bioactive constituents of MT and SJ and their molecular mechanism toward AChE inhibition. Bioassay-guided isolation afforded prenylflavonoids 1–3 from MT and anacardic acid derivatives 4 and 5 from SJ that were confirmed by NMR and MS data. Compound 5 exerted the strongest anti-AChE potential (IC50: 0.54 μM), followed by 1, 4, 3, and 2 (IC50: 1.0, 2.4, 6.8, and 33 μM, respectively). In silico molecular docking revealed 5 formed stronger molecular interactions including three H-bonds than its derivative 4 based on the saturation of their alkyl chains. The addition of a five carbon-prenyl chain in 1 increased the number of binding interactions, justifying its greater activity than derivatives 2 and 3. This research reflects the first report of AChE inhibitors from these species, thereby adding pharmacological values to MT and SJ as potential remedies in neuroprotection.

Phenolic Composition, In-vitro Antioxidant and Enzyme Inhibition Activities of Cardaria draba Different Parts

The plant Cardaria draba (L.) Desv. subsp. draba (Brassicaceae), is traditionally used for various ailments in different cultures. We investigated different solvent extracts such as methanol, ethanol, and water extracts obtained from flowers, leaves, stems, and roots of C. draba for their chemical composition, as well as antioxidant and enzyme inhibition activities of acetylcholinesterase (AChE), butyrylcholinesterase (BChE), α-glucosidase, α-amylase, and tyrosinase). RP-HPLC technique was used to determine the phenolic profile of each extracts. The antioxidant activities of the extracts were determined by using DPPH and ABTS method, total phenol and flavonoid content analysis, and iron chelating assay. Enzyme inhibitory potential was evaluated by 96-microplate method. According to the results, aqueous extract of flower demonstrated the highest total phenolic content (64.32 µgGAE/ mg), while leaf ethanol extract showed the highest total flavonoid content (141.47 µgQE/ mg) among all extracts. The methanol, and water extracts of flowers were the most effective DPPH scavenger while aqueous extract of flower was the most active on ABTS scavenging. It is shown that the extracts possess promising activity against α-glucosidase than α-amylase enzyme. The methanolic extract of flower showed anti-acetylcholinesterase activity, and the ethanolic extract of the stem exhibited the best anti-butyrylcholinesterase activity among the 12 extracts. As for the anti-tyrosinase activity, higher kojic acid equivalent values were found for the aqueous extracts of roots and leaves. In conclusion, the data obtained from this study may serve as the basis for the bioassay-guided isolation of active compounds and the development of novel drugs from Cardaria draba.

Exploration of essential oil from Psychotria poeppigiana as an anti-hyperalgesic and anti-acetylcholinesterase agent: Chemical composition, biological activity and molecular docking

Ethnopharmacological relevanceLeaves from Psychotria poeppigiana Müll. Arg. (accepted as Palicourea tomentosa (Aubl.) Borhidi), Rubiaceae, has traditionally been used in medicine for treatments of inflammation and pain; Synonymously, Cephaelis elata for the treatment of dementia; However, few scientific studies have been evidence demonstrating this activity. Aim of the studyThe aim of this study was to investigate the chemical composition of P. poeppigiana essential oil obtained from leaves (EOPP) and its antioxidant, anti-inflammatory and acetylcholinesterase (AChE) activities. Molecular docking simulations were carried out with the main constituents. Materials and methodsEOPP (hydrodistillation) was analysed by gas chromatography-mass spectrometry (GC–MS). The fractionation of EOPP afforded germacrene D and bicyclogermacrene. The antioxidant activity of EOPP was determined by MDA assay. The inflammatory parameters were evaluated using CFA model (with paw edema, mechanical, thermal hyperalgesia, MPO and NAG) in EOPP (30, 100 and 300 mg/kg), germacrene D and bicyclogermacrene (30 mg/kg). The AChE inhibition was evaluated in rat brain structures and molecular docking simulations were carried out using Autodock v.4.3.2. ResultsGC-MS analysis identified 19 compounds, and the major compounds were germacrene D (29.38%) and bicyclogermacrene (25.21%). EOPP exhibited high antioxidant capacity (IC50 = 12.78 ± 1.36 μg/mL). All the tested doses of EOPP and both major constituents significantly inhibited cold and mechanical hyperalgesia and significantly blocked the increase in MPO activity 24 h after the CFA injection. There was significant AChE inhibition by EOPP and germacrene D in the cerebral cortex and hippocampus (>50%). Enzyme-ligand molecular modelling showed that the major constituents of EOPP interacted differently with AChE. ConclusionsThe chemical compounds of the essential oil from the leaves of P. poeppigiana is based mainly on terpenes, the sesquiterpenes germacrene D (29.38%) and bicyclogermacrene (25.21%) being the major compounds. EOPP presented antioxidant, anti-inflammatory and anti-acetylcholinesterase (AChE) activities. Besides, enzyme-ligand molecular modelling showed the EOPP may act as an anti-hyperalgesic and AChE inhibitory agent. Taken together, these results might be in accordance with if folk use for pain- and inflammation-related symptoms.

Baoshanmycin and a New Furanone Derivative from a Soil-Derived Actinomycete, Amycolatopsis sp. YNNP 00208.

Actinomycetes have being regarded as a treasure reservoir of various bioactive secondary metabolites and devoted many antibiotics in clinicals. Amycolatopsis sp. YNNP 00208 was isolated from a soil sample collected in Gaoligong Mountain area, Yunnan Province, China. Chemical investigation of its fermentation broth led to a new amide, baoshanmycin (1), and a new furanone derivative, 3-(1,3-dihydroxybutyl)-4-methylfuran-2(H)-one (2), together with eight known compounds, including two amides (3-4), four cyclic dipeptides (5-8), and two deoxyribonucleosides (9-10). Their structures were established on basis of the 1D- and 2D-NMR spectroscopic data, along with the HR-ESI-MS experiments. Baoshanmycin (1) showed moderate antimicrobial activities against Candida albicans, and weak activities against Staphylococcus aureus, multi-drug resistant Staphylococcus aureus, Bacillus subtilis, Listeria monocytogenes, fluconazole-resistant Candida albicans. Baoshanmycin (1) presented strong antioxidant activity and moderate anti-acetylcholinesterase activity. The other compound 3-(1,3-dihydroxybutyl)-4-methylfuran-2(H)-one (2) and the known compounds (3-10) showed moderate antioxidant activity.

In vitro studies of a series of synthetic compounds for their anti-acetylcholinesterase activities identified arylpyrano[2,3-f]coumarins as hit compounds

Alzheimer's disease is one of the most widespread neurodegenerative diseases in the world. Until now, the drugs used to control this disease have been developed to target acetylcholinesterase (AChE). With the aim to identify new pharmacophores that can promisingly inhibit this enzyme, a library of 72 compounds belonging to chalcones, pyranochromenes, chromenes, pyranopyrazoles and dihydropyridines, was evaluated against AChE. Nineteen of these compounds are newly reported and among the tested compounds, seven, bearing a pyranochromene skeleton, showed inhibitory effects with IC50 values ranging from 9.01 to 32.39 µM. The most potent was identified as 8-amino-10-(4-bromophenyl)-5‑hydroxy-4-methyl-2-oxo-2,10-dihydropyrano[2,3-f]chromeno-9-carbonitrile. In silico studies using human recombinant acetylcholinesterase (PDB: 4EY7) showed important proximities between the NH2 group of this compound and E202 in AChE, between W86 and the OH-5 group, between W86 and the aromatic bicyclic system (π-π stacking, 4.2 Å), and between Y133 and both the OH-7 and the NH2 groups. These pyranochromenes emerged as a promising prototype for the development of new candidates against AChE.