Identification of non-alkaloid acetylcholinesterase inhibitors from Ferulago campestris (Besser) Grecescu (Apiaceae)

Inhibition of Acetylcholinesterase (AChE) is still considered as a strategy for the treatment of neurological disorders such as Alzheimer's disease. Many plant derived alkaloids (such as galantamine and rivastigmine) are known for their AChE inhibitory activity. Recently, other classes of natural compounds such as terpenoids, sesquiterpene glycosides and coumarins have been studied as new AChE inhibitors, with the aim to discover less toxic compounds compared to alkaloidal ones. The Ferulago campestris roots dichloromethane extract was used for a bioassay-guided fractionation for the search of AChE inhibitors. Three coumarin derivatives (umbelliprenin 1, coladonin 2 and coladin 3), three daucane ester derivatives (siol anisate 4, ferutinin 5 and 1-acetyl-5-angeloyl lapiferol 6), two phenol derivatives (2-epilaserine 7 and epielmanticine 8) and one polyacetylene (9-epoxyfalcarindiol 9) were isolated by the bioassay-guided approach. Their structures were characterized on the basis of spectral methods (1D and 2D NMR, and MS spectroscopy). All the isolated compounds were able to inhibit the AChE (IC₅₀ 1.2–0.1 mM) although at higher doses if compared to galantamine (6.7 μM) measured in the same conditions. The most active compounds were the daucane derivative siol anisate 4 and the epielmanticine 8, with IC₅₀ of 0.172 and 0.175 mM respectively.     

小叶臭黄皮的化学成分研究

从小叶臭黄皮(Clausena excavata Burm F.)的茎和叶中分离得到10个单萜基香豆素,分别鉴定为7-((E)-3'-甲基-4'-(8'-羰基-7',9'-烯-呋喃)-2'-烯)-香豆素(1)、7-((E)-3'-甲基-4'-(7'-甲基-8'-羰基-6'-烯-呋喃)-2'-烯)-香豆素(2)、7-((E)-3'-甲基-4'-(7'-甲基-6'-亚甲基-8'-羰基-呋喃)-2'-烯)-香豆素(3)、7-((E)-3'-甲基-4'-(9'-羟基-8'-羰基-6'-烯-呋喃)-2'-烯)-香豆素(4)、7-(3'-甲基-4'-(7'-甲基-8'-羰基-6'-烯-呋喃)-2',3'-环氧丁烷)-香豆素(5)、7-(3'-甲基-4'-(9'-羟基-8'-羰基-6'-烯-呋喃)-2',3'-环氧丁烷)-香豆素(6)、7-(3'-甲基-4'-(7'-甲基-7'-羟基-8'-羰基-6'-烯-呋喃)-2',3'-环氧丁烷)-香豆素(7)、7-(3'-甲基-4'-(7'-甲基-8'-羰基-呋喃)-2',3'-环氧丁烷)-香豆素(8)、5'-羟基葡萄内酯(9)和7-((E)-7'-羟基-3',7'-二甲基-2',5'-二烯)-香豆素(10),2个四降三萜,鉴定为11β-羟基-1α-乙酰基黄柏酮(11)、11β-羟基黄柏酮(12)和1个木脂素,鉴定为(-)-丁香脂素(13)。其中化合物11和13为首次从该植物中分离得到。测定了化合物1、2、3、11和12对癌细胞株A549、Hela和BGC-823的细胞毒活性,及其对白色念珠菌(Candida albicans)、金黄色葡萄球菌(Staphylococcus aureus)的抑菌活性。结果显示,化合物1对Hela和A549均有细胞毒活性,其半数抑制质量浓度(IC_(50))值分别为11.26和13.55 mg/L,化合物3对BGC-823有细胞毒活性,其IC_(50)值为16.65 mg/L,5个化合物对白色念珠菌和金黄色葡萄球菌均没有抗菌活性。     

Coumarins from the aerial part of Halocnemum strobilaceum

Four known coumarins, coumarin (1), 7-hydroxy-3-methylcoumarin (2), oreoselone (3) and heraclenin (4), were isolated from aerial part of Halocnemum strobilaceum. Their structures were determined by 1 and 2-D NMR techniques.     

Flavonoids with antiplasmodial and cytotoxic activities of Macaranga triloba

A new flavanone derivative, malaysianone A (1), four prenylated flavanones, 6-prenyl-3'-methoxyeriodictyol (2), nymphaeol B (3), nymphaeol C (4) and 6-farnesyl-3',4',5,7-tetrahydroxyflavanone (5), and two coumarins, 5,7-dihydroxycoumarin (6) and scopoletin (7), were isolated from the dichloromethane extract of the inflorescences of Macaranga triloba. The structures of these compounds were elucidated based on spectroscopic methods including nuclear magnetic resonance (NMR-1D and 2D), UV, IR and mass spectrometry. The cytotoxic activity of the compounds was tested against several cell lines, with 5 inhibiting very strongly the growth of HeLa and HL-60 cells (IC(50): 1.3 μg/ml and 3.3 μg/ml, respectively). Compound 5 also showed strong antiplasmodial activity (IC(50): 0.06 μM).     

Proanthocyanidins and a phloroglucinol derivative from Rumex acetosa L.

From the ethyl acetate soluble fraction of an acetone–water extract of the aerial parts of Rumex acetosa L. (Polygonaceae), a variety of monomeric flavan-3-ols (catechin, epicatechin, epicatechin-3-O-gallate), A- and B-type procyanidins and propelargonidins (15 dimers, 7 trimers, 2 tetramers) were isolated with 5 so far unknown natural products. Dimers: procyanidin B1, B2, B3, B4, B5, B7, A2, epiafzelechin-(4β→8)-epicatechin, epiafzelechin-(4β→8)-epicatechin-3-O-gallate (new natural product), epiafzelechin-(4β→6)-epicatechin-3-O-gallate (new natural product), epiafzelechin-3-O-gallate-(4β→8)-epicatechin-3-O-gallate, B2-3′-O-gallate, B2-3,3′-di-O-gallate, B5-3′-O-gallate, and B5-3,3′-di-O-gallate. Trimers: procyanidin C1, epiafzelechin-(4β→8)-epicatechin-(4β→8)-epicatechin (new natural product), epicatechin-(4β→8)-epicatechin-(4β→8)-catechin, cinnamtannin B1, cinnamtannin B1-3-O-gallate (new natural product), tentatively epicatechin-(2β→7, 4β→8)-epiafzelechin-(4α→8)-epicatechin (new natural product), and epicatechin-3-O-gallate-(4β→8)-epicatechin-3-O-gallate-(4β→8)-epicatechin-3-O-gallate.Tetramers: procyanidin D1 and parameritannin A1. All compounds were elucidated by ESI-MS, CD spectra, 1D- and 2D-NMR experiments as free phenols or peracetylated derivatives and, in part, after partial acid-catalysed degradation with phloroglucinol.A more abundant proanthocyanidin polymer was also isolated, purified and its chemical composition studied by ¹³C NMR.In addition a so far unknown phloroglucinolglycoside (1-O-β-d-(2,4-dihydroxy-6-methoxyphenyl)-6-O-(4-hydroxy-3,5-dimethoxybenzoyl)-glucopyranoside) was isolated.     

Two new O-geranyl coumarins from the resinous exudate of Haplopappus multifolius

From the resinous exudate of leaves of Haplopappus multifolius two new coumarins were isolated and assigned the structures 6-hydroxy-7-(5'-hydroxy-3',7'-dimethylocta-2',6'-dien)-oxycoumarin (1) and 6-hydroxy-7-(7'-hydroxy-3',7'-dimethylocta-2',5'-dien)-oxy coumarin (2).     

In vivo antidepressant activity of sesquiterpenes from the roots of Valeriana fauriei Briq

Antidepressant activity-guided fractionation of the MeOH extract of Valeriana fauriei Briq. roots resulted in the isolation of two new germacrane-type sesquiterpenes (1-2) in addition to seven known ones (3-9). Their structures were elucidated as 1β,10α-dihydroxyl-8α-acetoxyl-10β,11,11-trimethyl-4-formyl-bicyclogermacren-E-4(5)-ene (1), 1β-hydroxyl-8α-acetoxyl-11,11-dimethyl-4-formyl-bicyclogermacren-E-4(5),10(14)-diene (2), bicyclo[8,1,0]5β-hydroxyl-7β-1acetoxyl-5α,11,11'-trimethyl -E-1(10)-ene-4α,15-olide (3), 8α-acetoxyl-3α,4α,10-trihydroxyl-guaia-1(2)-ene-12,6α-olide (4), 2-Ethylhexyl-4-hydroxybenzoate (5), 11αH-gemacra-1(10)E,4Z-diene-3-one-12,6α-olide (6), β-Sitoterol (7), isovaleric acid (8), isoborneol acetate (9), using a combination of UV, IR, mass spectroscopy, 1D and 2D NMR spectroscopy. The antidepressant activity of compounds 1-4 was investigated by the FST on mice. Among them, compounds 3 and 4 showed the significant antidepressant activity (*, P<0.01).     

Chromones and coumarins from the dried fructus of Cnidium monnieri

Chemical investigations on the ethanolic extract of the dried fructus of Cnidium monnieri offered three chromones and eight coumarins. Among them, a new chromone and a new coumarin were identified and elucidated as 5,7-dihydroxy-6-[(2Z)-4-(β-d-glucopyranosyl)oxy-3- methylbut-2-enyl]-2-hydroxymethyl-4H-1-benzopyran-4-one (1, hydroxycnidimoside A) and (rel 1′S,2′R)-8-(2,3-epoxy-1-hydroxy-3-methylbutyl)-7-methoxycoumarin (8, hydroxyosthole epoxide), respectively, by extensive analyses of spectroscopic data including 1- and 2-D NMR, MS, UV, OR, IR, and HRMS data. The other known compounds were identified by analyses of spectroscopic data and by comparison with literature reported.     

A new dilignan from Cynara cardunculus

A new dilignan, 7,8-trans-7',8'-trans-7",8"-cis-7"',8"'-cis-8,8'-trans-4",4"',7',9,9",9"'-hexahydroxy-3,3',3",3"'-tetramethoxy-4,8":4',8"':5,7":5',7"'-tetraoxy-7,9'-epoxy-8,8'-dilignan-7'-ol, named cynarinine (2), was isolated together with the known tracheloside (1) from the seeds of Cynara cardunculus.     

A new flavanol from Daphne genkwa

A new flavanol, 5, 7, 4'-trihydroxy-8-ethoxycarbonylflavanol (1), was isolated from the ethanol extract of Daphne genkwa Sieb. et Zucc. Its structure was defined by spectroscopic methods.     

Lignans ofChamaecyparis obtusa

Heartwood ofChamaecyparis obtusa contains significant amounts of a dibenzylbutyrolactone lignan, hinokinin (8). This investigation demonstrated that the contents of 8 and a norlignan, hinokiresinol (12), were higher in the heartwood region than in the sapwood, indicating their nature of being heartwood extractives. Eleven lignans — xanthoxylol (1), 7-oxohinokinin (2), savinin (3), dihydrosesamin (4), isoactifolin (5), sesamin (6), piperitol (7), hinokinin (8), pluviatolide (9), haplomyrfolin (10), and rnatairesinol (11) — were isolated from young shoots ofChamaecyparis obtusa cv. Breviramea. Eight lignans (1, 2, 4, 5, 7, 9,10, and11) were isolated from this plant for the first time. Chiral high-performance liquid Chromatographie analysis showed that8, 9, 10, and11, were found to be levorotatory and optically pure (>99% e.e.). Based on the chemical structures of the isolated lignans, possible biosynthetic pathways of8 are discussed.Parts of this report were presented at the 44th annual meeting of the Japan Wood Research Society, Nara, April 1994; the 46th annual meeting of the Japan Wood Research Society, Kumamoto, April 1996; and the 44th Lignin Symposium, Gifu, October 1999     

NorA efflux pump inhibitory activity of coumarins from Mesua ferrea

The purpose of this investigation was to study the modulator and efflux pump inhibitor activity of coumarins isolated from Mesua ferrea against clinical strains as well as NorA-over expressed strain of Staphylococcus aureus 1199B. Seven coumarins were tested for modulator activity using ethidium bromide (EtBr) as a substrate. Compounds 1, 4–7 modulated the MIC of EtBr by ≥ 2 fold against wild type clinical strains of S. aureus 1199 and S. aureus 1199B, whereas compounds 4–7 modulated the MIC of EtBr by ≥ 16 fold against MRSA 831. Compounds 1, 4–7 also reduced the MIC of norfloxacin by ≥ 8 fold against S. aureus 1199B, and 4–6 reduced the MIC of norfloxacin by ≥ 8 fold against MRSA 831 at half of their MICs. Inhibition of EtBr efflux by NorA-overproducing S. aureus 1199B and MRSA 831 confirmed the role of compounds 4–6 as NorA efflux pump inhibitors (EPI). Dose-dependent activity at sub-inhibitory concentration (6.25 μg/mL) suggested that compounds 4 and 5 are promising EPI compared to verapamil against 1199B and MRSA 831 strains.     

Constituents from the roots of <Emphasis Type="Italic">Taxus cuspidata</Emphasis>

The known propelargonidin, afzelechin-(48)-afzelechin (1), the known lignans 7-hydroxynortrachelogenin (2), epinortrachelogenin (3), nortrachelogenin (4), hydroxymatairesinol (5), allohydroxymatairesinol (6), matairesinol (7), oxomatairesinol (8), and isotaxiresinol (9), and the known taxoids taxinine M (10), taxayuntin (11), and 10-deacetyltaxol (12), and 10-deacetylbaccatin III (13) were isolated from the roots of Taxus cuspidata (Japanese yew, Taxaceae). The propelargonidin was isolated from Taxus spp. for the first time, and was detected in the roots, bark, and twigs.     

Phytochemical and antifungal studies on Terminalia mollis and Terminalia brachystemma

Phytochemical investigation of the stem bark of Terminalia mollis afforded friedelin (1), catechin with epicatechin (2), gallocatechin with epigallocatechin (3) and 3-O-methylellagic acid 4'-O-α-rhamnopyranoside (4). Arjunolic acid with 2α, 3β, 23-trihydroxy-urs-12-en-28-oic acid (5), 2α-hydroxyursolic acid (6), gallic acid (7), chebulanin (8) and 2'-O-galloylvitexin (9) were isolated from the leaf. Chebulanin (8), betulinic acid (10), ursolic acid (11), catechin (12), isoorientin (13), orientin (14), isovitexin (15) and punicalagin (16) were isolated from Terminalia brachystemma leaf. The first full unambiguous NMR assignments for (4) and (8), and revised assignments for (9), are reported. Compound (16) showed good activity against three Candida species.     

A new irregular diterpenoid from Opopanax chironium

The ethereal extract of the roots of Opopanax chironium yielded peucelinenoxide acetate (1), a new natural product with an irregular diterpene skeleton, besides the known coumarins gaudichaudin, columbianadin, peucedanin and officinalin isobutyrate.     

A new lupene triterpenetriol and anticholinesterase activity of Salvia sclareoides

A new lupene triterpenetriol was isolated from the acetone extract of the aerial parts of Salvia sclareoides and characterised as (1beta,3beta)-lup-20(29)-ene-1,3,30-triol (1). In addition, nepetidin (2), nepeticin (3), lupendiol (4), (1beta,11alpha)-dihydroxy-lup-20(29)-en-3-one (5), ursolic acid (6), sumaresinolic acid (7) and hederagenin (8), were identified in this Salvia sp. To the best of our knowledge, the compounds 2 and 7 are new constituents in Salvia spp. The acetone, ethanol, butanol and water extracts of the plant were screened for the in vitro inhibitory activity of acetylcholinesterase (AChE) and butyrilcholinesterase (BChE), enzymes which play a role in the Alzheimer disease. All extracts inhibited acetylcholinesterase activity at 10 microg/ml, a remarkable activity since the standard drug rivastigmine does not inhibit acetylcholinesterase at the same concentration. Regarding the butyrilcholinesterase, the acetone extract at 1000 microg/ml was able to inhibit completely the enzyme activity and the butanol and ethanol extracts, at this concentration, produced a potent inhibition of BchE.     

Sesquiterpenoids from Trichoderma atroviride, an endophytic fungus in Cephalotaxus fortunei

Two new sesquiterpenoids, identified as (rel 1S, 3R, 4R, 7R)-3-[5-hydroxy-4-methylpent-3-enyl]-1, 3, 7-trimethyl-2-oxabicyclo [2, 2, 1] heptane (1) and (rel 1S, 3R, 4R, 7R)-3-[3, 4-dihydroxy-4-methylpentyl]-1, 3, 7-trimethyl-2-oxabicyclo [2, 2, 1] heptane (2), were isolated from cultures of Trichoderma atroviride (strain no. S361), an endophytic fungal strain residing in the bark of Cephalotaxus fortunei. The structures of compounds 1 and 2 were elucidated by detailed spectroscopic analyses on the basis of NMR, IR, and MS data. Both compounds 1 and 2 were potent inhibitors on NO production in LPS-stimulated RAW264.7 cells, with IC₅₀ values of 15.3 and 9.1 μM, respectively.     

New neolignans from Talauma ovata

The hexane extract of the bark of Talauma ovata yielded three new natural neolignans, identified as acetyl oleiferin-C (4), acetyl oleiferin-F (7) and acetyl oleiferin-G (8), together with the known compounds dihydroguaiaretic acid (1), austrobailignan-5 (2), oleiferin-C (3), austrobailignan-6 (5) and oleiferin-F (6).     

Phenolics from Bidens bipinnata and their amylase inhibitory properties

A new chlorinated flavonoid, 3, 6, 8-trichloro-5, 7, 3', 4'-tetrahydroxyflavone (1), a new biscoumaric acid derivative, 4-O-(2″, 3″-O-diacetyl-6″-O-p-coumaroyl-β-d-glucopyranosyl)-p-coumaric acid (2), and 8, 3', 4'-trihydroxyflavone-7-O-β-d-glucopyranoside (3) together with twenty-four known compounds (4-27) were isolated from the whole plant of Bidens bipinnata. All chemical structures were established on the basis of UV-, MS- and NMR ((1)H, (13)C, (1)H-(1)H COSY, HMQC and HMBC) spectroscopic data. Some of the isolated compounds were tested for the inhibition of α-amylase. The result showed that isookanin (6) was a potent inhibitor of α-amylase (IC(50)=0.447mg/ml).     

银杏叶中烷基酚化合物的分离与鉴定

介绍了银杏叶烷基酚化合物的分离过程，并鉴定出烷基酚化合物单体3类6种，其中银杏酸类化合物2种，白果酚类化合物3种，白果二酚类化合物1种。这些化合物经UV、IR、MS、^1HNMR、^13CNMR等波谱鉴定为：3-（8-十五碳烯基）苯酚；3-[4（Z），7（Z）-十七碳二烯基]苯酚；3-（10-十七碳烯基）苯酚；6-（8-十五碳烯基）水杨酸；6（10-十七碳烯基）十七碳烯基）水杨酸；5-（8-十五碳烯基）间苯二酚。