Outlining In Vitro and In Silico Cholinesterase Inhibitory Activity of Twenty-Four Natural Products of Various Chemical Classes: Smilagenin, Kokusaginine, and Methyl Rosmarinate as Emboldening Inhibitors.

Cholinesterase (ChE) inhibition is an important treatment strategy for Alzheimer's disease (AD) as acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) are involved in the pathology of AD. In the current work, ChE inhibitory potential of twenty-four natural products from different chemical classes (i.e., diosgenin, hecogenin, rockogenin, smilagenin, tigogenin, astrasieversianins II and X, astragalosides I, IV, and VI, cyclocanthosides E and G, macrophyllosaponins A-D, kokusaginin, lamiide, forsythoside B, verbascoside, alyssonoside, ipolamide, methyl rosmarinate, and luteolin-7-O-glucuronide) was examined using ELISA microtiter assay. Among them, only smilagenin and kokusaginine displayed inhibitory action against AChE (IC50 = 43.29 ± 1.38 and 70.24 ± 2.87 µg/mL, respectively). BChE was inhibited by only methyl rosmarinate and kokusaginine (IC50 = 41.46 ± 2.83 and 61.40 ± 3.67 µg/mL, respectively). IC50 values for galantamine as the reference drug were 1.33 ± 0.11 µg/mL for AChE and 52.31 ± 3.04 µg/mL for BChE. Molecular docking experiments showed that the orientation of smilagenin and kokusaginine was mainly driven by the interactions with the peripheral anionic site (PAS) comprising residues of hAChE, while kokusaginine and methyl rosmarinate were able to access deeper into the active gorge in hBChE. Our data indicate that similagenin, kokusaginine, and methyl rosmarinate could be hit compounds for designing novel anti-Alzheimer agents.

Medicinal Plants Used in the Treatment of Human Immunodeficiency Virus.

Since the beginning of the epidemic, human immunodeficiency virus (HIV) has infected around 70 million people worldwide, most of whom reside is sub-Saharan Africa. There have been very promising developments in the treatment of HIV with anti-retroviral drug cocktails. However, drug resistance to anti-HIV drugs is emerging, and many people infected with HIV have adverse reactions or do not have ready access to currently available HIV chemotherapies. Thus, there is a need to discover new anti-HIV agents to supplement our current arsenal of anti-HIV drugs and to provide therapeutic options for populations with limited resources or access to currently efficacious chemotherapies. Plant-derived natural products continue to serve as a reservoir for the discovery of new medicines, including anti-HIV agents. This review presents a survey of plants that have shown anti-HIV activity, both in vitro and in vivo.

Anti-hepatitis B activity of isoquinoline alkaloids of plant origin.

Hepatitis B virus (HBV) is the causative agent of B-type hepatitis in humans, a vaccine-preventable disease. Despite the availability of effective vaccines, globally, 2 billion people show evidence of past or current HBV infection, of which 350 million people are persistently infected, with an estimated annual increase of 1 million. There is no cure for chronic HBV infections, which are associated with cirrhotic liver failure and with an increased risk of developing hepatocellular carcinoma. Hepatitis antiviral research has focused primarily on the development of inhibitors of viral polymerase through the use of nucleoside analogues. Therefore, there is an urgent need for the development of non-nucleoside compounds to be used as an alternative or to complement the current therapy. To address this need, 18 isoquinoline alkaloids were evaluated for their potential antiviral activity against HBV in vitro.

Cholinesterase Inhibitory and In Silico Toxicity Assessment of Thirty-Four Isoquinoline Alkaloids - Berberine as the Lead Compound.

BACKGROUND: Cholinesterase (ChE) inhibitors used currently in clinics for the treatment of Alzheimer's disease (AD) are the most prescribed drug class with nitrogen-containing chemical formula. Galanthamine, the latest generation anti-ChE drug, contains an isoquinoline structure. OBJECTIVE: The aim of the current study was to investigate the inhibitory potential of thirty-four isoquinoline alkaloids, e.g. (-)-adlumidine, ß-allocryptopine, berberine, (+)-bicuculline, (-)-bicuculline, (+)-bulbocapnine, (-)-canadine, (±)-chelidimerine, corydaldine, (±)-corydalidzine, (-)-corydalmine, (+)-cularicine, dehydrocavidine, (+)-fumariline, (-)-fumarophycine, (+)-α-hydrastine, (+)-isoboldine, 13-methylcolumbamine, (-)-norjuziphine, norsanguinarine, (-)-ophiocarpine, (-)-ophiocarpine-N-oxide, oxocularine, oxosarcocapnine, palmatine, (+)-parfumine, protopine, (+)-reticuline, sanguinarine, (+)-scoulerine, (±)-sibiricine, (±)-sibiricine acetate, (-)-sinactine, and (-)-stylopine isolated from several Fumaria (fumitory) and Corydalis species towards acetyl- (AChE) and butyrylcholinesterase (BChE) by microtiter plate assays. The alkaloids with strong ChE inhibition were proceeded to molecular docking simulations as well as in silico toxicity screening for their mutagenic capacity through VEGA QSAR (AMES test) consensus model and VEGA platform as statistical approaches. The inputs were evaluated in a simplified molecular input-line entry system (SMILES). RESULTS: ChE inhibition assays indicated that the highest AChE inhibition was caused by berberine (IC50: 0.72 ± 0.04 µg/mL), palmatine (IC50: 6.29 ± 0.61 µg/mL), ß-allocryptopine (IC50: 10.62 ± 0.45 µg/mL), (-)-sinactine (IC50: 11.94 ± 0.44 µg/mL), and dehydrocavidine (IC50: 15.01 ± 1.87 µg/mL) as compared to that of galanthamine (IC50: 0.74 ± 0.01 µg/mL), the reference drug with isoquinoline skeleton. Less number of the tested alkaloids exhibited notable BChE inhibition. Among them, berberine (IC50: 7.67 ± 0.36 µg/mL) and (-)-corydalmine (IC50: 7.78 ± 0.38 µg/mL) displayed a stronger inhibition than that of galanthamine (IC50: 12.02 ± 0.25 µg/mL). The mutagenic activity was shown for ß-allocryptopine, (+)- and (-)-bicuculline, (±)-corydalidzine, (-)-corydalmine, (+)-cularicine, (-)-fumarophycine, (-)-norjuziphine, (-)-ophiocarpine-N-oxide, (+)-scoulerine, (-)-sinactine, and (-)-stylopine by means of in silico experiments. The results obtained by molecular docking simulations of berberine, palmatine, and (-)-corydalmine suggested that the estimated free ligand-binding energies of these compounds inside the binding domains of their targets are reasonable to make them capable of establishing strong polar and nonpolar bonds with the atoms of the active site amino acids. CONCLUSION: Our findings revealed that berberine, palmatin, and (-)-corydalmine stand out as the most promising isoquinoline alkaloids in terms of ChE inhibition. Among them, berberine has displayed a robust dual inhibition against both ChEs and could be evaluated further as a lead compound for AD.

A new sesquiterpene, prosoterpene, from Prosopis africana (Guill. & Perr.) Taub.

A new sesquiterpene (Prosoterpene, 1) and eleven reported compounds (2-12) of several classes, such as flavonoids, alkaloids, phenolic acids, and long-chain alcohols, were isolated from the BuOH extract of Prosopis africana (Guill. & Perr.) Taub. Compounds 2-10 were reported for the first time from this plant. Isomers 11 and 12 were separated for the first time. Extensive spectroscopic techniques and literature comparisons were used to characterise their structures. Furthermore, compounds 3, 5-8, and 10-12 were performed for anti-glycation and cytotoxicity activities. Compound 3 (quercetin-3-O-α-L-rhamnoside) exhibited moderate anti-glycation activity. All tested compounds were non-cytotoxic against MCF-7 (breast cancer), NCI-H460 (lung cancer), Hela (cervical cancer), and BJ (normal human fibroblast) cell lines.

In-vitro neuroprotective properties of the Maydis stigma extracts from four corn varieties.

Neuroprotective effect of the ethyl acetate and ethanol extracts of the silks of four Zea mays L. varieties (var. intendata, var. indurata, var. everta and var. saccharata) was evaluated by acetylcholinesterase, butrylcholinesterase and tyrosinase inhibitions and by antioxidant activity tests against 2,2-diphenyl-1-picrylhydrazyl and superoxide as well as two iron-related antioxidant methods (iron-chelation capacity and ferric-reducing antioxidant power). Total phenol and flavonoid contents in the extracts were determined spectrophotometrically.

Assessment of antimicrobial, insecticidal and genotoxic effects of Melia azedarach L. (chinaberry) naturalized in Anatolia.

In this study, antibacterial, antifungal, insecticidal and genotoxic activities of the fruit and leaf extracts of Melia azedarach of Turkish origin were evaluated for the first time. The antimicrobial activity was assessed against Gram (+) and (-) bacteria, four Candida species and three dermatophytic fungus (Trichophyton rubrum, Epidermophyton floccosum and Microsporum gypseum). The insecticidal activity of the methanolic fruit extract was performed against the larvae of Aedes aegpyti, Culex pipiens and Culex quinquefasciatus. The genotoxicity of this extract was evaluated against Drosophila melanogaster by somatic mutation and recombination test. The extracts showed higher antibacterial effect against Gram (-) strains (16-32 µg ml(-1) of minimal inhibition concentration, MIC), while the leaf extracts were more effective on Candida albicans (32 µg ml(-1)of MIC). The extracts did not exhibit insecticidal activity and genotoxicity. Total phenol and flavonoid contents of the extracts were determined spectrophotometrically, and the ethyl acetate extract of the leaves was the richest in total flavonoids.

A new steroidal alkaloid from Fritillaria michailovskyi Fomin.

A new steroidal alkaloid, michainine (1), was isolated from Fritillaria michailovskyi Fomin, along with nine known compounds 2-10 of different classes, including ribonucleoside, steroids, and fatty acids, which were isolated for the first time from this plant. Their structures were elucidated through extensive spectroscopic techniques, as well as by comparing the data in the literature. Furthermore, the dichloromethane fraction of F. michailovskyi showed a positive butyrylcholinesterase inhibitory activity, along with non-cytotoxicity against 3T3 cell line.

Urtica dioica-Derived Phytochemicals for Pharmacological and Therapeutic Applications.

Urtica dioica belongs to the Urticaceae family and is found in many countries around the world. This plant contains a broad range of phytochemicals, such as phenolic compounds, sterols, fatty acids, alkaloids, terpenoids, flavonoids, and lignans, that have been widely reported for their excellent pharmacological activities, including antiviral, antimicrobial, antihelmintic, anticancer, nephroprotective, hepatoprotective, cardioprotective, antiarthritis, antidiabetic, antiendometriosis, antioxidant, anti-inflammatory, and antiaging effects. In this regard, this review highlights fresh insight into the medicinal use, chemical composition, pharmacological properties, and safety profile of U. dioica to guide future works to thoroughly estimate their clinical value.

Triterpene saponins from Cyclamen trocopteranthum.

Two new triterpene saponins ( 1- 2) together with three known saponins, deglucocyclamin I ( 3), cyclamin ( 4), and mirabilin ( 5), were isolated from the tubers of Cyclamen trocopteranthum. They were elucidated as 3 beta- O-{4- O-[3-hydroxyl-3-methylglutaryl]- beta-D-xylopyranosyl-(1 --> 2)- beta-D-glucopyranosyl-(1 --> 4)-[ beta-D-glucopyranosyl-(1 --> 2)]- alpha-L-arabinopyranosyl}-16 alpha-hydroxy-13 beta,28-epoxy-oleanan-30-al ( 1) and 3 beta- O-{4- O-[3-hydroxyl-3-methylglutaryl]- beta-D-xylopyranosyl-(1 --> 2)-[ beta-D-glucopyranosyl-(1 --> 6)]- beta-D-glucopyranosyl-(1 --> 4)-[ beta-D-glucopyranosyl-(1 --> 2)]- alpha-L-arabinopyranosyl}-16 alpha-hydroxy-20,30-lactone-olean-12-ene ( 2). Their structures were characterized mainly by a combination of 1D- and 2D-NMR techniques ( (1)H- (1)H COSY, TOCSY, NOESY, HSQC, and HMBC) and mass spectroscopy. Saponins 1, 3, and 4 showed a weak cytotoxic activity when tested against HT-29 and HCT 116 tumor colon cancer cells.

Inhibitory activity of marine sponge-derived natural products against parasitic protozoa.

In this study, thirteen sponge-derived terpenoids, including five linear furanoterpenes: furospinulosin-1 (1), furospinulosin-2 (2), furospongin-1 (3), furospongin-4 (4), and demethylfurospongin-4 (5); four linear meroterpenes: 2-(hexaprenylmethyl)-2-methylchromenol (6), 4-hydroxy-3-octaprenylbenzoic acid (7), 4-hydroxy-3-tetraprenyl-phenylacetic acid (8), and heptaprenyl-p-quinol (9); a linear triterpene, squalene (10); two spongian-type diterpenes dorisenone D (11) and 11 beta-acetoxyspongi-12-en-16-one (12); a scalarane-type sesterterpene; 12-epi-deoxoscalarin (13), as well as an indole alkaloid, tryptophol (14) were screened for their in vitro activity against four parasitic protozoa; Trypanosoma brucei rhodesiense, Trypanosoma cruzi, Leishmania donovani and Plasmodium falciparum. Cytotoxic potential of the compounds on mammalian cells was also assessed. All compounds were active against T. brucei rhodesiense, with compound 8 being the most potent (IC(50) 0.60 microg/mL), whereas 9 and 12 were the most active compounds against T. cruzi, with IC(50) values around 4 microg/mL. Compound 12 showed the strongest leishmanicidal activity (IC(50) 0.75 microg/mL), which was comparable to that of miltefosine (IC(50) 0.20 microg/mL). The best antiplasmodial effect was exerted by compound 11 (IC(50) 0.43 microg/mL), followed by compounds 7, 10, and 12 with IC(50) values around 1 microg/mL. Compounds 9, 11 and 12 exhibited, besides their antiprotozoal activity, also some cytotoxicity, whereas all other compounds had low or no cytotoxicity towards the mammalian cell line. This is the first report of antiprotozoal activity of marine metabolites 1-14, and points out the potential of marine sponges in discovery of new antiprotozoal lead compounds.

Assessment of enzyme inhibitory and antioxidant activities of lignans from Taxus baccata L.

Phytochemical investigations of Taxus baccata L. by successive chromatographic methods resulted in the isolation of the lignans lariciresinol (1), taxiresinol (2), 3'-demethylisolariciresinol-9'-hydroxyisopropylether (3), isolariciresinol (4), and 3-demethylisolariciresinol (5) as well as taxoids. Compounds 1-5 were evaluated for their acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and lipoxygenase (LOX) inhibitory activities, which play a role in the pathogenesis of Alzheimer's disease (AD), by in vitro spectrophotometric methods, while they were also screened for their antioxidant capacity in 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging, ferrous ion-chelating effect, and ferric-reducing antioxidant power (FRAP) at 125, 250, 500, and 1000 microg ml(-1). All compounds exhibited a moderate inhibition against both BChE and LOX, whereas they were inactive towards AChE. The compounds displayed a great scavenging activity against DPPH especially at 500 and 1000 microg ml(-1). Besides, they were found to exert noteworthy reducing antioxidant power on ferric ions. In particular, the FRAP of compounds 2 (3.552 +/- 0.02), 4 (3.021 +/- 0.71), and 5 (3.533 +/- 0.01) were as high as that of the reference chlorogenic acid (3.618 +/- 0.01) at 1000 microg ml(-1). None of the compounds exhibited chelating ability against ferrous ions.

Preliminary screening of acetylcholinesterase inhibitory and antioxidant activities of Anatolian Heptaptera species.

The ethyl acetate and methanol extracts prepared from the fruits, aerial parts, and roots of Heptaptera anatolica (Boiss.) Tutin, (Umbelliferae), H. anisoptera (DC.) Tutin, H. cilicica (Boiss. & Balansa) Tutin (endemic), and H. triquetra (Vent.) Tutin were tested for their acetylcholinesterase (AChE) inhibitory and antioxidant activities. AChE inhibition was evaluated using ELISA microplate reader at 500, 1000, and 2000 microg mL(-1). Antioxidant activity was determined by 2,2-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging test and Fe(+2)-ferrozine test system for metal chelating power at the same concentrations. Total phenol contents of the extracts were determined using Folin-Ciocalteu reagent. At 2000 microg mL(-1), only the aerial parts and fruits of H. anatolica showed moderate anti-AChE effect (61.97% and 49.80%, respectively), while the aerial parts and fruits of H. triquetra had the highest DPPH scavenging effect (80.48% and 86.19%, respectively). All of the methanol extracts exhibited significant ferrous ion-chelating effect varying between 72.97% and 92.36%, whereas only four of the ethyl acetate extracts exerted chelating effect over 70%. These results indicate that Heptaptera species could be a good source for antioxidant compounds.

Essential oil compositions and antioxidant properties of the roots of twelve Anatolian Paeonia taxa with special reference to chromosome counts.

Essential oil compositions and antioxidant potentials of fourteen ethanol (75%) root extracts prepared from twelve taxa of the genus Paeonia (Paeoniaceae), including P. arietina Anders., P. daurica Andrews, P. xkayae N. Ozhatay, P. kesrouanensis Thiéb., P. mascula (L.) Miller subsp. arasicola G. Kaynak, ö. Yilmaz & R. Daskin, P. mascula (L.) Miller subsp. bodurii N. Ozhatay, P. cf. mascula L. (Mill.) subsp. mascula (two samples from central and northeastern Anatolia), P. cf. officinalis Retz., P. peregrina Miller (two samples from western and northwestern Anatolia), P. tenuifolia L., P. turcica Davis & Cullen, and P. wittmanniana Hartwiss ex Lindl. were assessed. The chromosome numbers of the root tips of the species were examined using chromosome staining technique with Shiff's reagent under Leitz microscope. The essential oils of the roots of the Paeonia species were analyzed by gas chromatography (GC) and gas chromatography-mass spectrometry (GC-MS) and the major components were identified as salicylaldehyde (10%-94.4%), cis-myrtanal (5.5%-59.7%), and methyl salicylate (2%-52.2%). Antioxidant potentials were tested against 1,1-diphenyl-2-picrylhydrazyl (DPPH) and nitric oxide (NO) radicals using propyl gallate and rutin as the references. Total phenolic contents of the ethanol extracts were determined using Folin-Ciocalteau's method. The extracts exerted moderate NO scavenger effect and displayed insignificant DPPH radical scavenger activity at 500 microg mL(-1). On the other hand, P. daurica, P. tenuifolia and P. cf. mascula subsp. mascula are diploids with 2n = 10, while other nine taxa are tetraploids with 2n = 20.

The Therapeutic Potential of Anthocyanins: Current Approaches Based on Their Molecular Mechanism of Action.

Anthocyanins are natural phenolic pigments with biological activity. They are well-known to have potent antioxidant and antiinflammatory activity, which explains the various biological effects reported for these substances suggesting their antidiabetic and anticancer activities, and their role in cardiovascular and neuroprotective prevention. This review aims to comprehensively analyze different studies performed on this class of compounds, their bioavailability and their therapeutic potential. An in-depth look in preclinical, in vitro and in vivo, and clinical studies indicates the preventive effects of anthocyanins on cardioprotection, neuroprotection, antiobesity as well as their antidiabetes and anticancer effects.

Estimation of anti-inflammatory, antinociceptive and antioxidant activities of Arctium minus (Hill) Bernh. ssp. minus.

ETHNOPHARMACOLOGICAL RELEVANCE: Arctium minus (Hill) Bernh. ssp. minus (Asteraceae) leaves are used to alleviate rheumatic pain, against fever and sunstroke with externally application in Turkish folk medicine. AIM OF THE STUDY: To evaluate the anti-inflammatory, antinociceptive and antioxidant activities of aqueous and ethanol extracts prepared from the leaves of Arctium minus ssp. minus. MATERIALS AND METHODS: The ethanolic and aqueous extracts from the leaves of Arctium minus ssp. minus were evaluated in mice for anti-inflammatory activity using carrageenan-induced hind paw edema model and for antinociceptive activity using p-benzoquinone-induced abdominal contractions test. Moreover, the antioxidant power of the extracts has been determined by using 1,1-diphenyl-2-picrylhydrazyl (DPPH) and flow injection analysis-luminol chemiluminescence (FIA-CL). In addition, the total phenolic content in both extracts was determined with spectrophotometric method. RESULTS: Our results showed that only the ethanol extract exhibited a dose-dependent anti-inflammatory activity ranging between 11.1 and 23.6% at 200mg/kg dose as well as displayed a significant antinociceptive activity without inducing any gastric damage. Although, both extracts were shown to possess significant DPPH radical-scavenging activity, that of aqueous extract was found to have more pronounced activity. In FIA-CL system, the ethanol extract was shown to possess a significant scavenger activity against H(2)O(2) while the aqueous extract was much more potent antioxidant activity against HOCl-luminol CL than ethanol extract. CONCLUSION: According to our results, it was concluded that Arctium minus ssp. minus contains potent natural antioxidants. In this study, in vivo experimental results have also supported the folk medicinal utilization of Arctium minus ssp. minus.

Dioscorea Plants: A Genus Rich in Vital Nutra-pharmaceuticals-A Review.

Dioscorea species, known as "Yams," belong to family Dioscoreaceae. This genus consists of more than 600 species distributed from Africa, Asia, the Caribbean's South America, and the South Pacific islands. Their organoleptic properties make them the most widely used carbohydrate food and dietary supplements. The underground and/or aerial tubers represent valuable sources of proteins, fats, and vitamins for millions of people in West Africa. This review gives a shot of secondary metabolites of Dioscorea plants, including steroids, clerodane diterpenes, quinones, cyanidins, phenolics, diarylheptanoids, and nitrogen-containing compounds. This review collected the evidence on biological properties of description Dioscorea, including in-vitro and in-vivo studies. Dioscorea species contain promising bioactive molecules i.e. diosgenin that support their different biological properties, including antioxidant, hypoglycaemic, hypolipidemic, anti- antimicrobial, inflammatory, antiproliferative, androgenic, estrogenic, and contraceptive drugs. Indeed, besides its nutrient values, Dioscorea is a potential source of bioactive substances of interest in the prevention/treatment of several diseases, and thus represents a great challenge in developing countries. However, ethnomedicinal potential should be validated and further researches on pharmacological properties and phytochemical composition should be carried out. Particularly, doing some studies to convert the preclinical results to clinical efficacy should be guaranteed. Dioscorea, Food plant, Traditional use, Phytochemistry, Pharmacological activities.

Berberis Plants-Drifting from Farm to Food Applications, Phytotherapy, and Phytopharmacology.

The genus Berberis includes about 500 different species and commonly grown in Europe, the United States, South Asia, and some northern areas of Iran and Pakistan. Leaves and fruits can be prepared as food flavorings, juices, and teas. Phytochemical analysis of these species has reported alkaloids, tannins, phenolic compounds and oleanolic acid, among others. Moreover, p-cymene, limonene and ocimene as major compounds in essential oils were found by gas chromatography. Berberis is an important group of the plants having enormous potential in the food and pharmaceutical industry, since they possess several properties, including antioxidant, antimicrobial, anticancer activities. Here we would like to review the biological properties of the phytoconstituents of this genus. We emphasize the cultivation control in order to obtain the main bioactive compounds, the antioxidant and antimicrobial properties in order to apply them for food preservation and for treating several diseases, such as cancer, diabetes or Alzheimer. However, further study is needed to confirm the biological efficacy as well as, the toxicity.

Inhibitory effect of Turkish Rosmarinus officinalis L. on acetylcholinesterase and butyrylcholinesterase enzymes.

In the current study, we have tested acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activity of the petroleum ether, ethyl acetate, chloroform, and methanol extracts, rosmarinic acid as well as the essential oil obtained from Rosmarinus officinalis L. growing in Turkey by a spectrophotometric method of Ellman using ELISA microplate-reader at 0.2,0.5, and 1.0mg/mL concentrations. In addition, quantification of rosmarinic acid, a common phenolic acid found in rosemary, was carried out by reversed-phase HPLC in the methanolic extract of the plant, which was found to have 12.21±0.95% (122.1±9.5mg/g extract) of rosmarinic acid. Rosmarinic acid was also tested for its AChE and BChE inhibitory effect and found to cause 85.8% of inhibition against AChE at only 1.0mg/mL. Besides, the essential oil was analyzed by GC-MS technique, which was shown to be dominated by 1,8-cineol (44.42%) and followed by α-pinene (12.57%).

Coumarin, anthroquinone and stilbene derivatives with anticholinesterase activity.

Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) are the key enzymes in pathogenesis of Alzheimer's disease (AD), which is characterized by a deficit in central cholinergic transmission. In the current study, AChE and BChE inhibitory activities of seven coumarin derivatives [umbelliferone (1), 4-methylumbelliferone (2), 4-hydroxycoumarin (3), scopoletin (4), 8-methoxypsoralen (5), bergapten (6), and iso-bergapten (7)], a furanocoumarin mixture obtained from Heracleum crenatifolium Boiss. (Umbelliferae), as well as of two anthroquinone derivatives [rhein (8) and aloe-emodine (9)] and one stilbene, rhapontin (10), were tested by the spectrophotometric method of Ellman using an ELISA microplate-reader at 1 mg mL(-1). Among them, the furanocoumarin mixture [(68.8 +/- 0.76)%], bergapten [(62.4 +/- 0.74)%], aloe-emodine [(57.2 +/- 1.32)%], scopoletin [(53.1 +/- 0.83)%], and 4-methylumbelliferone [(62.3 +/- 1.03)%] showed over 50% inhibition against AchE, while umbelliferone [(54.3 +/- 0.23)%], 4-methylumbelliferone [(80.9 +/- 1.17)%], scopoletin [(73.5 +/- 1.01)%], 8-methoxypsoralen [(67.1 +/- 0.98)%], as well as the furanocoumarin mixture [(76.7 +/- 0.95)%] had a notable anti-BChE effect.