Anti-acetylcholinesterase Activity Research Articles

Lawsonia inermis flower aqueous extract expressed better anti-alpha-glucosidase and anti-acetylcholinesterase activity and their molecular dynamics

Lawsonia inermis (henna) has been used in traditional medicine throughout the world and biological property of its flower has been least explored. In the present study, the phytochemical characterization and biological activity (in vitro radical scavenging activity, anti-alpha glucosidase and anti-acetylcholinesterase) of aqueous extract prepared from henna flower (HFAE) was carried out by both Qualitative and quantitative phytochemical analysis and Fourier-transform infrared spectroscopy revealed the functional group of the phytoconstituents such as phenolics, flavonoids, saponin, tannins and glycosides. The phytochemicals present in HFAE was preliminary identified by liquid chromatography/electrospray ionization tandem mass spectrometry. The HFAE showed potent in vitro antioxidant activity and the HFAE inhibited mammalian α-glucosidase (IC50 = 129.1 ± 5.3 µg/ml; Ki = 38.92 µg/ml) and acetylcholinesterase (AChE; IC50 = 137.77 ± 3.5 µg/ml; Ki = 35.71 µg/ml) activity by competitive manner. In silico molecular docking analysis revealed the interaction of active constituents identified in HFAE with human α-glucosidase and AChE. Molecular dynamics simulation for 100 ns showed the stable binding of top two ligand/enzyme complexes with lowest binding energy such as 1,2,3,6-Tetrakis-O-galloyl-beta-D-glucose (TGBG)/human α-glucosidase, Kaempferol 3-glucoside-7-rhamnoside (KGR)/α-glucosidase, agrimonolide 6-O-β-D-glucopyranoside (AMLG)/human AChE and KGR/AChE. Through MM/GBSA analysis, the binding energy for TGBG/human α-glucosidase, KGR/α-glucosidase, AMLG/human AChE and KGR/AChE was found to be −46.3216, −28.5772, −45.0077 and −47.0956 kcal/mol, respectively. Altogether, HFAE showed an excellent antioxidant, anti-alpha glucosidase and anti-AChE activity under in vitro. This study suggest HFAE with remarkable biological activities could be further explored for therapeutics against type 2 diabetes and diabetes-associated cognitive decline.Communicated by Ramaswamy H. Sarma

Antibiotic Guanacastane Diterpenoids with Two New Skeletons from Psathyrella candolleana Uncovered by Semisolid and Liquid Media

The culture of Psathyrella candolleana in host Dioscorea opposite medium produced seven new guanacastane diterpenoids, psayamin (1) as an unprecedented 5/7/6/6/6/6/7/5-fused octacyclic spiro scaffold both under liquid and semisolid conditions, psathins A-C (4-6) with a 5/7/6 tricyclic backbone by liquid medium, psathins D-E (7-8) as the same unprecedented skeletons of 5/6/7/6-fused tetracyclic or 6/7/6 tricyclic structures, and psathin F (9) with a 5/7/5/6 tetracyclic backbone by semisolid medium. The structures were elucidated by detailed spectroscopic analyses and those of 1 and 7 were determined by single-crystal X-ray crystallography. The semisolid culture led to four structure types of the guanacastane diterpenoid. Compound 5 showed antifungal activity against phytopathogen Fusarium incarnatum with a minimum inhibitory concentration (MIC) of 8 μg/mL, while compound 4 showed significant antifungal activity against Alternaria sp. with an MIC of 2 μg/mL. Compounds 1 and 8 also showed antifeedant activities against the silkworms with the feeding deterrence indices of 50%, at the concentrations of 50 μg/cm2. Compound 1 showed significant cytotoxicity with IC50 at 10.87 ± 0.24-15.96 ± 0.30 μM and anti-acetylcholinesterase activity with IC50 at 37.3 μM. Also, compound 1 remarkably induced apoptosis of HL-60 at 10, 20 μM in a concentration-dependent manner. The spiral ring of 1 was vital in cytotoxicity and anti-acetylcholinesterase activity. The different media fermented by P. candolleana resulted in the chemical diversity of bioactive guanacastane diterpenoids and potential applications in the agricultural and food functions.

Compounds from the Petroleum Ether Extract of Wedelia chinensis with Cytotoxic, Anticholinesterase, Antioxidant, and Antimicrobial Activities.

Wedelia chinensis is a folk medicine used in many Asian countries to treat various ailments. Earlier investigations reported that the petroleum ether extract of the plant has potential biological activity, but the compounds responsible for activity are not yet completely known. Therefore, the current work was designed to isolate and characterize the compounds from the petroleum ether extract and to study their bioactivities. Four compounds including two diterepenes (-) kaur-16α-hydroxy-19-oic acid (1) and (-) kaur-16-en-19-oic acid (2), and two steroids β-sitosterol (3), and cholesta-5,23-dien-3-ol (4) were isolated and characterized. Among the compounds, the diterpenes were found to have more biological activities than the steroidal compounds. Compound 1 showed the highest cytotoxicity with LC50 of 12.42 ± 0.87 μg/mL. Likewise, it possesses good antioxidant activity in terms of reducing power. On the contrary, compound 2 exerted the highest antiacetylcholinesterase and antibutyrylcholinesterase activity. Both the diterpenes showed almost similar antibacterial and antifungal activity. The identification of diterpenoid and steroid compounds with multifunctional activities suggests that W. chinensis may serve as an important source of bioactive compounds which should be further investigated in animal model for therapeutic potential in the treatment of different chronic diseases.

Polymer drug conjugates containing memantine, tacrine and cinnamic acid: promising nanotherapeutics for the treatment of Alzheimer’s disease

Aim To prepare polymer-drug conjugates containing a combination of memantine, tacrine, and E)-N-(3-aminopropyl)cinnamide, promising therapeutics for the treatment of neurodegenerative disorders. Methods The conjugates were characterised by 1HNMR, particle size analysis, SEM, LC-MS, TEM/EDX, and XRD, followed by in vitro anti-acetylcholinesterase and drug release studies. Results 1H NMR analysis revealed successful drug conjugation with drug mass percentages in the range of 1.3–6.0% w/w. The drug release from the conjugates was sustained for 10 h in the range of 20–36%. The conjugates’ capability to inhibit acetylcholinesterase (AChE) activity was significant with IC50 values in the range of 13–44.4 µm which was more effective than tacrine (IC50 =1698.8 µm). The docking studies further confirmed that the conjugation of the drugs into the polymer improved their anti-acetylcholinesterase activity. Conclusion The drug release profile, particle sizes, and in vitro studies revealed that the conjugates are promising therapeutics for treating neurodegenerative disorders.

Discovery of reversible selective monoamine oxidase B inhibitors with anti-acetylcholinesterase activity derived from 4-oxo-N-4-diphenyl butanamides.

Aim: Multitargeted drugs are essential for the treatment of various neurodegenerative disorders, because of their complex nature. This study aimed to develop novel small molecules as selective monoamine oxidase B (MAO-B) inhibitors with cholinesterase inhibition. Materials & methods: With the help of fragment-based drug design, some 4-oxo-N-4-diphenyl butanamides were designed and synthesized as MAO-B inhibitors with anti-acetylcholinesterase (AChE) activity. Results: Compound 6m showed the best neuroprotection, with reversible selective MAO-B inhibition activity (IC50 = 11.54±0.64nM). Compounds 6b, 6h, 6j, 6n and 6p (IC50 = 20.90±0.50, 17.25±0.90, 15.85±0.16, 16.81±0.85 and 25.19±0.17nM, respectively) also appeared as potent and selective MAO-B inhibitors with anti-AChE activity. Conclusion: The present study suggests potent, neuroprotective and nontoxic lead compounds as selective MAO-B inhibitors with anti-AChE activity.

Chemical composition and anti-acetylcholinesterase, nitric oxide suppressing activities of Piper betle leaves oil

Essential oil of Piper betle leaves in Quang Nam-Da Nang do obtain via the steam distillation method with oil collection efficiency reaching 0.83%. The chemical composition of the essential oil from Piper betle leaves in Quang Nam-Da Nang is determined via the GC-MS method that includes 21 components (99.68%), among which the main components are eugenol acetate (32.33%), eugenol (24.56%), 4-allyl-1,2-diacetoxybenzene (19.8%), germacrene D (5.98%), caryophyllene (3.32%), and γ-muurolene (2.45%). The essential oil of Piper betle leaves in Quang Nam-Da Nang also showed moderate anti-acetylcholinesterase activity with IC50 (µg/mL) = 65.94±5.96 and moderate nitric oxide suppressing activity with IC50 (µg/mL) = 46.69±3.57.

Anti-Acetylcholinesterase and Synergistic Antifungal Activities of Selected Salvia Species: Correlation with Metabolic Profiles

Salvia species are known for their anti-fungal and anti-acetylcholinesterase (AChE) activity. Metabolomics is defined as a comprehensive quantitative and qualitative analysis of large-scale of metabolites. In this study, besides determining anti-acetylcholinesterase and synergistic antifungal activities of selected Salvia species (S. cryptantha Montbret & Aucher ex Benth., S. tchihatcheffii (Fisch. & C. A. Mey.) Boiss., S. officinalis L., S. virgata Jacq.), the metabolite profiles were clarified and correlation analyzes between the activity results and profiles were carried out. Aerial parts of all plant materials were extracted by methanol to determine the metabolic profile by using GC-MS (Gas Chromatography-Mass Spectrometry) and LC-QTOF-MS (Liquid Chromatography Quadrupole Time of Flight Mass Spectrometry). Also, Ellman's spectrophotometric method for anti-acetylcholinesterase activity and the checkerboard method for synergistic antifungal activity between extracts and fluconazole were performed. 295 known and 1408 unknown metabolites were detected by using GC-MS while 346 known and 69008 unknown metabolites were by using LC-QTOF-MS. S. cryptantha, S. tchihatcheffii, S. officinalis, and S. virgata demonstrated inhibitory activities on AChE with the ratio of 32.72%, 5.9%, 43.96%, and 12.1% respectively at the concentration of 200 µg/mL. A synergism was found for all Salvia sp. against Candida tropicalis ATCC 750 strain (FICI values of ≤0.5). In addition, primary and secondary metabolites, which are highly correlated with both activities, were determined. All Salvia species exhibited synergic activity with fluconazole while having weak AChE inhibitory activity. Combining natural products with synthetic drugs is important in order to increase efficacy. At the same time, herbal products must be used carefully at the point of herb-drug interactions. Further studies are needed to investigate active metabolites according to correlation results.

Two new iridoids and triterpenoid analogues from the leaves of Viburnum chingii and their anti-acetylcholinesterase activity

Two undescribed split-ring iridoids (1–2) with six known triterpenes (3–8) and one steride (9) were isolated from the Viburnum chingii. Compound 2 possessed an unprecedented split-ring iridoid skeleton formed by electrocyclic reaction and split ring. The structures and absolute configurations of the new iridoids were established by NMR, HRESIMS, and ECD calculations. All the isolated compounds were tested for AChE inhibitory activity. Biologically, 1, 2, 3, 4, and 7 displayed significant AChE effects compared to the positive control donepezil, and have also been subjected to molecular docking studies.

Cucurbitane-type triterpenoids from the fruits of Citrullus colocynthis

A phytochemical investigation of the fruits of Citrullus colocynthis resulted in the isolation of 21 structurally diverse cucurbitane triterpenoids, including 9 previously undescribed ones, colocynins A-I (1–9). Their absolute configurations were elucidated by means of quantum chemical electronic circular dichroism (ECD) calculations, CD exciton chirality method, and single-crystal X-ray crystallography. Colocynins A-C (1–3) represent the first examples of nonanorcucurbitane-type triterpenoids. An anti-acetylcholinesterase activity assay showed that 6, 10, 13, 18, and 20 exhibited inhibitory activities, with IC50 values ranging from 5.0 to 21.7 μM. In addition, 18 and 21 showed significant cytotoxicity against PACA, A431, and HepG2 cells, with IC50 values ranging from 0.042 to 0.60 and 3.6–14.4 μM, respectively.

Bioassay Analysis and Molecular Docking Study Revealed the Potential Medicinal Activities of Active Compounds Polygonumins B, C and D from Polygonum minus (Persicaria minor).

Polygonumins B, C and D, derivative compounds of polygonumins A, were isolated from the stem of Polygonum minus. Based on NMR results, the structure of polygonumins derivatives is comprised of four phenylpropanoid units and a sucrose unit, with a similar structure to polygonumins A. However, the structural differences between polygonumins B (1), C (2) and D (3) can be distinguished based on the existence of methoxy, ethanoyl and hydroxyl groups and protons which bind to C-4, C-4′ and C-3″. Interestingly, these bioactive compounds showed various medicinal properties based on our investigation on antioxidant, anticholinesterase and anti-HIV-1 protease activities. The IC50 value of DPPH and ABTS (antioxidant activities) was in the following descending order: polygonumins B > polygonumins C > polygonumins A > polygonumins D. In addition, almost similar pattern of antioxidant activity was observed for anti-acetylcholinesterase activity based on its IC50 value in descending order: polygonumins B > polygonumins C > polygonumins D > polygonumins A. On the other hand, polygonumins C and D showed inhibition of HIV-1 protease activity more than the positive control, pepstatin A. Finally, molecular docking studies on AChE and BChE proteins were carried out in order to gain insight into the mode of interactions between these compounds and the active residues for both enzymes. These remarkable findings indicate that these compounds have potential to be developed as targeted drugs for Alzheimer’s disease or as anti-HIV drugs.

An Analysis of Commercial Noni Juice: LC-MS/MS Phenolic Profiles and Cytotoxic Activity

Fermented juice from the noni tree (Morinda citrifolia) is a traditional medicinal product used by South Pacific Islanders to treat a wide range of ailments, including cancer, inflammation and obesity, as well as improving overall wellbeing. Many of its bioactive properties have been suggested to arise from the high antioxidant capacity and phenolic content found in the juice. However, there have been limited investigations into the phenolic profiles of noni juice produced locally in the Pacific. This study aimed to investigate the chemical composition and bioactive properties of noni juice. The first phase of this study used liquid chromatography with tandem mass spectrometry (LC-MS/MS) to characterise the phenolic composition of five brands of commercial noni juice produced in the South Pacific region. A total of 21 phenolic compounds were putatively identified, with the most abundant generally being rutin, 4-hydroxybenzoic acid and gentisic acid. Vastly differing phenolic profiles were found between the noni juice brands. Significant differences were also found in their antioxidant capacities and total phenolic contents. Of the three major phenolic compounds identified, gentisic acid showed the highest antioxidant activity (640% higher than Trolox). Additionally, the noni juice showed no significant anti-acetylcholinesterase activity and no to moderate cytotoxicity against two cancer cell lines (HeLa and HT29). These results indicate that the phytochemical profiles—and hence, the expected bioactive properties—are likely to vary significantly between different noni juice brands. Furthermore, the anti-cancer activity of non-concentrated noni juice appears to be relatively low.

Synthesis, structural characterization and in vitro pharmacological properties of betanin-encapsulated chitosan nanoparticles

Betanin, a natural food color and the only betalain, is approved for use in pharmaceutical and food industries as natural antioxidative and preservative agent, respectively. However, the antioxidant power and health-promoting properties of betanin have been disregarded due to its low stability in physiological conditions. Therefore, this study is designed to synthesize and evaluate in vitro pharmacological characteristics of betanin-encapsulated chitosan nanoparticles (ChBetNPs). ChBetNPs were synthesized by ionic gelation method and characterized by DLS, UV, FTIR, SEM and zeta potential analysis. The encapsulation efficiency (EE) and in vitro release kinetics were analyzed using spectrophotometric technique for quantifying the encapsulated amount of betanin in ChBetNPs as a function of time. The antioxidant activity of ChBetNPs was analyzed by DPPH and H2O2 radical scavenging assays, anti-inflammatory activity by protein denaturation and human RBCs stabilization assays, and anti-acetylcholinesterase activity using standard protocol with minor modifications. Unloaded chitosan nanoparticles (CSNPs) were found to be sized at 161.4 ± 5.75 nm while an increase in the size to 270.3 ± 8.50 nm was noticed upon encapsulating betanin. EE of ChBetNPs was measured to be ∼87.5%. The IC50 of ChBetNPs depicted significant free radical scavenging activities as compared to CSNPs. Similarly, a strong anti-inflammatory activity of ChBetNPs was noted. Significant decrease in acetylcholinesterase activity by ChBetNPs was measured (IC50 0.5255 μg/mL vs. control 26.09 μg/mL). The vegetables coated with 3% ChBetNPs showed decreased weight loss as compared to uncoated control. ChBetNPs was shown to exhibit strong antioxidant, anti-inflammatory and anti-acetylcholinesterase activities thus making it a significant therapeutic agent for the management of Alzheimer's disease.

The anti-Alzheimer compounds from tempeh oil in LPS-induced neuronal Schwann cells

AbstractTempeh is a traditional fermented Indonesian food from white soybean. Tempe has better nutritional value than non-fermented white soybean. The aim of this study was to extract tempeh oil and analyze the inhibitory potency of Alzheimer-related gene expression in LPS-induced neuronal Schwann cells. Tempeh oil was extracted with Bligh Dyer method and was analyzed with PUFA identification, anticholinesterase activity, antioxidant activity, and quantitative PCR. Tempeh oil had a total yield of 7.14%, and PUFA identification found 8.37% omega-3. The anti-acetylcholinesterase activity showed that tempeh oil 25 µg/mL had the highest activity and 500 µg/mL in anti-butyrylcholinesterase activity. The quantitative PCR showed that tempeh oil had downregulated the gene expression of PSEN1, Gsk3b, cdk5, and TNF. From this study, tempeh oil may have the potential to lower the risk of Alzheimer’s disease by regulating certain gene traits.

Phlegcarines A-C, three Lycopodium alkaloids from Phlegmariurus carinatus (Desv. ex Poir.) Ching

Three undescribed Lycopodium alkaloids, phlegcarines A-C, along with nine known alkaloids, were isolated from the aerial parts of a gardening clubmoss Phlegmariurus carinatus (Desv. ex Poir.) Ching. Phlegcarine A is an undescribed Lycopodium alkaloid possessing an unprecedented 5/9/6/6 fused-tetracyclic ring system consisting of an oxa-cyclononanone, a piperidine, a methylcyclohaxane and an oxazolidine. Phlegcarine B is the first N-chloromethyl piperidinium Lycopodium alkaloid of (+)-lycoflexine. The semi-synthesis of phlegcarine B was investigated from (+)-fawcettimine. Phlegcarine C, an undescribed epimer of 12-epilycodoline, is a rare lycopodine-type alkaloid with β-oriented H-4. Transformation of phlegcarine C and lycodoline to 12-epilycopodine N-oxide via keto-enol tautomerization was investigated using m-CPBA. The structural assignments were established through comprehensive spectroscopic techniques and chemical correlations. Phlegcarines A-C were assayed for their anti-acetylcholinesterase activity, but none of them exhibited biological activity more potent than that of huperzine A.

Antioxidant and enzyme inhibition activities of Spartium junceum with HPLC-DAD profiling

Spartium junceum L., a Fabaceae plant, is commonly known as Spanish broom and cultivated in the Mediterranean regions. This study aimed to investigate the chemical profiles and antioxidant and different enzyme inhibitory activities of methanol, ethanol and aqueous extracts obtained from flowers and stems of S. junceum. Also, their phenolic compositions were analyzed by high-performance liquid chromatography with a diode-array detector (HPLC-DAD). The aqueous extract of stems showed the highest phenolic content (63.94 mg gallic acid equivalents/g), while the aqueous extract of stems contained the highest flavonoid content (61.33 mg quercetin equivalents/g). The stem water extract demonstrated the highest 2,2′-diphenyl-1-picrylhydrazyl radical-scavenging activity (IC50: 2327 μg/ml), while the stem water extract exhibited a strong 2,2′-azino-di(3-ethylbenzothiazoline-6-sulfonic acid) radical-scavenging activity (IC50: 91.80 ± 0.90 μg/ml). The tested extracts differed greatly in terms of enzyme inhibition activity. The stem water extract showed the highest anti-acetylcholinesterase activity (IC50: 46.69 ± 1.66 μg/ml); however, the stem methanol extract exhibited a strong anti-butyrylcholinesterase activity (IC50: 76.39 ± 0.27 μg/ml). The flower methanol extract was the most active against the α-glucosidase enzyme (IC50: 296.7 ± 3.77 μg/ml). All extracts showed low activities against α-amylase and tyrosinase enzymes. The evaluation of the biological activity results provides evidence for bioactivity-guided isolation studies on the active extracts of this plant.

Identification of Antioxidants and Acetylcholinesterase Inhibitors from Hapaline benthamiana Schott. Using at Line LC-ESI-QTOF MS/MS

In this work, total phenolics, total flavonoids, antioxidant activity, and acetylcholinesterase inhibition potency of Hapaline benthamiana schott are reported. In addition, the investigation of antioxidant and anti-acetylcholinesterase compounds of this plant coupled to the at line-LC-ESI-QTOF-MS/MS technique is introduced for the first time. The results show that the methanolic extract contains the highest amount of total phenolics, total flavonoids, antioxidant activity, and acetylcholinesterase inhibition activity. The at line-LC-ESI-QTOF-MS/MS technique has provided information on the biological activity of each compound while mass spectrometry provided information on their molecular weights. Based on their mass spectra, 53 compounds were identified with most of them being phenolic, flavonoid, and glycolipid compounds. Seventeen compounds exhibited a strong antioxidant activity ranging between 51.52 - 63.58 % inhibition whereas one compound, namely septentriodine, showed a strong acetylcholinesterase inhibitory effect of more than 50 %. This study indicates that Hapaline benthamiana schott is a source of active compounds containing antioxidant and anti-acetylcholinesterase activities with health benefits. In addition, at line-LC-ESI-QTOF-MS/MS has been shown to be an effective technique for the rapid and simultaneous analyses of antioxidant and anti-acetylcholinesterase compounds in plant extracts. HIGHLIGHTS Investigation of antioxidants and acetylcholinesterase inhibitors from Hapaline benthamiana Schott coupled to at line-LC-ESI-QTOF-MS/MS technique is reported for the first time Fifty-three compounds from methanolic extract were successfully identified Eighteen compounds exhibited strong biological activity This technique is a rapid and valuable tool for the identification of lead compounds in complex extracts and for the investigation of their bioactivity GRAPHICAL ABSTRACT

Variation in essential oil composition within and among Tunisian Thymus algeriensis Boiss et Reut. (Lamiaceae) populations: Effect of ecological factors and incidence on antiacetylcholinesterase and antioxidant activities

The variation of the essential oil composition of fourteen Tunisian Thymus algeriensis populations and their antioxidant and antiacetylcholinesterase activities were assessed. At the species level, α-pinene, 1,8-cineole, camphor, caryophyllene oxide and carvacrol were the main compounds. Significant variation in the essential oil composition was observed between populations according to ecological factors. Six chemotypes were revealed (1,8-cineole-β-panasinsene/1,8-cineole/caryophyllene oxide/1,8-cineole-camphor-caryophyllene oxide/1,8-cineole-camphor-caryophyllene oxide-terpenyl acetate/carvacrol) with the distinction of upper arid populations (Ta 13 and Ta 14) with the dominance of carvacrol chemotype. The occurrence of the carvacrol was positively correlated to the evapotranspiration, summer drought stress and the temperature of the warmest months of the year.High chemical intrapopulation variability was also observed, revealing the presence of seven chemotypes (carvacrol/terpenyl acetate/caryophyllene oxide/linalool-linalyl acetate/1,8-cineole-β-panasinsene/1,8-cineole/1,8-cineole-camphor). The level of antioxidant and anti-acetylcholinesterase activity was linked to their chemical composition difference. The best activities were revealed for populations Ta 13 and Ta 14 from the most arid zones, characterized by their carvacrol richness.

In Vitro Screening for Anti-Acetylcholinesterase and Antioxidant Activities of Hottonia palustris L. Extracts and Their Unusual Flavonoids.

Hottonia palustris L. is from the genus Hottonia (Primulaceae), and the understanding of its phytochemical and pharmacological properties is limited. In this study, the use of chromatographic techniques led to the isolation of a further eleven compounds, including three new flavonoids: 2',5-dihydroxyflavone 2'-O-β-glucopyranoside, 5,6-dihydroxyflavone 6-O-(6"-O-glucopyranosyl)-β-glucopyranoside (hottonioside A), and 4',5,7-trihydroxyflavone 7-O-(2"-O-β-glucuronide)-β-glucopyranoside. Their structures were determined using extensive 1D and 2D NMR data and mass spectrometry (HRMS). The qualitative assessment of the chemical composition of the investigated extracts and fractions was performed using the LC-HRMS technique. Furthermore, the antioxidant potential of extracts, fractions, and compounds and their ability to inhibit acetylcholinesterase were also evaluated. Thus, we may conclude that the observed biological effects are the result of the presence of many biologically active compounds, of which dibenzoylmethane is the most active. Therefore, H. palustris is a source of substances with desirable properties in the prevention and treatment of neurodegenerative diseases.

Divulging the anti-acetylcholinesterase activity of Colletotrichum lentis strain KU1 extract as sustainable AChE active site inhibitors.

Alzheimer's disease (AD), also called senile dementia is a neurodegenerative disease seen commonly in the elderly and is characterised by the formation of β-amyloid plaques and neurofibrillary tangles (NFT). Though a complete understanding of the disease is lacking, recent studies showed the role of the enzyme acetylcholinesterase (AChE) in pathogenesis. Finding new lead compounds from natural sources has always been a quest for researchers. Endophytic fungi are a set of microbes that reside within plants without causing any harm. This study focuses on screening endophytes for the production of active acetylcholinesterase inhibitors. Five endophytic fungi were isolated from Catharanthus roseus and screened for AChE inhibitory activity. Three isolates were found to inhibit AChE inhibitory activity and were distinguished based on molecular and microscopic methods. The mycelial extract was taken for the bioassay-guided column chromatography and TLC was performed on the active fraction. The GC-MS and NMR analysis identified the active compounds in the extract as 9-hexadecen-1-ol and erucamide. Molecular docking studies revealed that the compounds are thermodynamically feasible and have significant glide scores. Computational studies revealed that the hydroxyl group of 9-hexadecen-1-ol forms a hydrogen bond with Ser 293 in the active site of AChE, whereas the active site interactions were predominantly hydrophobic in the case of erucamide and are reflected in AChE inhibition assays.

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.