Bioactive phenolic amides from Celtis africana

Nine compounds have been isolated for the first time from Celtis africana, namely trans-N-coumaroyltyramine (1), trans-N-feruloyltyramine (2), trans-N-caffeoyltyramine (3), lauric acid (4), oleic acid (5), palmitic acid (6), lupeol (7), β-sitosterol (8) and oleanolic acid (9), respectively. Their structures have been elucidated by different spectroscopic techniques. The isolated compounds were screened for their antioxidant, anti-inflammatory and acetylcholinestrease enzyme inhibitory activities. Compounds 1-3 showed significant antioxidant and anti-inflammatory activities and weak to moderate acetylcholinestrease enzyme inhibition activity.     

Tyrosinase inhibitory potential of natural products isolated from various medicinal plants

Seven secondary metabolites, p-hydroxybenzoic acid (1), 3,4-dihydroxybenzoic acid (2), ferulic acid (3), 2,6-dimethoxy-4-hydroxy acetophenone (4), lupeol (5), 2'-O-ethylmurrangatin (6) and hibiscetin heptamethyl ether (7) were the natural products isolated from various medicinal plants. Their structures were identified by spectral comparison with previously reported data. The compounds 1-7 were screened for their tyrosinase-inhibitory activity. The compound p-hydroxybenzoic acid (1) was found to have potent activity against tyrosinase enzyme, whereas lupeol (5) showed significant activity.     

Purification of angiotensin‐converting enzyme from human plasma and investigation of the effect of some active ingredients isolated from Nigella sativa L. extract on the enzyme activity

In the present study, one‐step purification of angiotensin‐converting enzyme (ACE, peptidyldipeptidase A, EC 3.4.15.1), responsible for regulation of blood pressure, was achieved using affinity chromatography from human plasma. The enzyme was purified 12,860‐fold with a specific activtiy of 5080 EU/mg protein. Optimum temperature and pH were determined for the enzyme as 35–40°C and pH 7.4–7.5, respectively. The purity of ACE was determined by SDS–PAGE and the enzyme showed two bands at 60 and 70 kDa on the gel. The native molecular weight of ACE was found to be 260 kDa by gel filtration chromatography, demonstrating that the enzyme has a heterodimeric structure. Natural fatty acids of Nigella sativa (Ranunculaceae) were isolated by means of column chromatography. The structures of these compounds were determined using NMR and GC‐MS. The results showed that high concentrations of linoleic, oleic and palmitic acids were isolated from the plant. The effect of six fractions (Fr 1–6) on ACE activity was examined. Fraction 3 increased the ACE activity while the other fractions decreased the enzyme activity. The concentrations of the fractions inhibiting the half‐maximum activity of the enzyme were calculated as 1.597 mg/mL for Fr 1, 0.053 mg/mL for Fr 2, 0.527 mg/mL for Fr 4, 0.044 mg/mL for Fr 5 and 0.136 mg/mL for Fr 6 using a Lineweaver–Burk graph.     

New Urea Biosensor Based on Urease Enzyme Obtained from Helycobacter pylori

The urease enzyme of Helicobacter pylori was isolated from biopsy sample obtained from antrum big curvature cell extracts. A new urea biosensor was prepared by immobilizing urease enzyme isolated from Helicobacter pylori on poly(vinylchloride) (PVC) ammonium membrane electrode by using nonactine as an ammonium ionophore. The effect of pH, buffer concentration, and temperature for the biosensor prepared with urease from H. pylori were obtained as 6.0, 5 mM, and 25 °C, respectively. We also investigated urease concentration, stirring rate, and enzyme immobilization procedures in response to urea of the enzyme electrode. The linear working range of the biosensor extends from 1 × 10(-5) to 1 × 10(-2) M and they showed an apparent Nernstian response within this range. Urea enzyme electrodes prepared with urease enzymes obtained from H. pylori and Jack bean based on PVC membrane ammonium-selective electrode showed very good analytical parameters: high sensitivity, dynamic stability over 2 months with less decrease of sensitivity, response time 1-2 min. The analytical characteristics were investigated and were compared those of the urea biosensor prepared with urease enzyme isolated from Jack bean prepared at the same conditions. It was observed that rapid determinations of human serum urea amounts were also made possible with both biosensors.     

Enzyme inhibiting lignans from Vitex negundo

Two new lignans trivially named negundins A (1) and B (2), were isolated along with (+)-diasyringaresinol (3), (+)-lyoniresinol (4), vitrofolal E (5) and vitrofolal F (6), reported for the first time from this species. The structures of the new compounds were established through spectral studies. Compound 2 showed potent inhibitory activity against lipoxygenase enzyme, while 5 showed moderate activity against butyryl-cholinesterase.     

Investigation of the effects of natural compounds isolated from Arum rupicola var. rupicola on glutathione reductase enzyme purified from bovine liver

Glutathione reductase (GR, E.C. 1.8.1.7), a flavoenzyme, is responsible for recycling of oxidized glutathione disulfide. This study was performed in two main sections. In the first GR was purified from bovine liver by affinity column chromatography and the purification rate and specific activity of the enzyme were calculated as 1832‐fold and 141 EU/mg protein, respectively. The subunit molecular weight of the enzyme was determined as 55 kDa by means of SDS–PAGE. The second section isolated natural components of Arum rupicola Boiss. var. rupicola using column chromatography. The isolation protocol for this plant was performed with a series of different‐sized columns with hexane–ethyl acetate. According to the thin‐layer chromatography plate, seven substances (R1–R7) were isolated. Our study's aim was to find new activators or inhibitors for GR activity. With this aim, all isolated substances were tested for GR activity. R6 showed competitive inhibition, while R4 had noncompetitive inhibition of GR activity. R1 played a role as an activator of GR activity. The inhibitory activity percentage vs. concentration graph was plotted. Values of IC₅₀ for R4 and R6 were calculated as 0.193 mg/mL and 3.98 μg/mL, respectively, from the equation of this graph.     

Xanthine oxidase inhibiting flavonol glycoside from Amberboa ramosa

A new flavonol glycoside (1) has been isolated from the ethyl acetate soluble fraction of Amberboa ramosa and assigned the structure 5,7,4'-trihydroxy-3,8-dimethoxylflavone 5-O-beta-D-gluco-pyranoside (1). In addition, 6,4'-dihydroxy-3,5,7-trimethoxyflavone (2), 5,7-dihydroxy-4'-methoxyflavone (3) and (23R)-5alpha-cycloart-24-ene-3beta,21,23-triol (4) have also been reported for the first time from this species. The structures were deduced on the basis of 1D and 2D NMR techniques. The compounds 1-3 displayed weak to moderate inhibition against the xanthine oxidase enzyme.     

Tyrosinase inhibitors from Rhododendron collettianum and their structure-activity relationship (SAR) studies

A new coumarinolignoid 8'-epi-cleomiscosin A (1) together with the new glycoside 8-O-beta-D-glucopyranosyl-6-hydroxy-2-methyl-4H-1-benzopyrane-4-one (2) have been isolated from the aerial parts of Rhododendron collettianum and their structures determined on the basis of spectroscopic evidences. Tyrosinase inhibition study of these compounds and their structure-activity relationship (SAR) were also investigated. The compounds exhibited potent to mild inhibition activity against the enzyme. Especially, the compound 1 showed strong inhibition (IC50=1.33 microM) against the enzyme tyrosinase, as compared to the standard tyrosinase inhibitors kojic acid (IC50=16.67 microM) and L-mimosine (IC50=3.68 microM), indicating its potential used for the treatment of hyperpigmentation associated with the high production of melanocytes.     

COX-1, COX-2 inhibitors and antifungal agents from Croton hutchinsonianus

Two new compounds, 3'-(4'-hydroxy-3',5'-dimethoxyphenyl)-propyl benzoate (1) and 3'-(4'-hydroxyphenyl)-propyl benzoate (3) together with known compounds, 3'-(4'-hydroxy-3'-methoxyphenyl)-propyl benzoate (2), poilaneic acid (4), farnesyl acetone (5) and 4-hydroxybenzaldehyde (6) were isolated and identified from the branches of Croton hutchinsonianus. Their structures were determined by spectroscopic methods. The three phenylpropyl benzoates (1-3) were found to exhibit antifungal activity against Candida albicans (IC(50) 5.36-11.41 microg/ml). Compounds 1-2 (IC(50) 2.11-4.95 microg/ml) exhibited potent but non-selective activity against the enzymes cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) whereas 3 (IC(50) 1.88 microg/ml) preferentially inhibited the enzyme COX-2.     

Free radical scavenging phenylethanoid glycosides from Leucas indica Linn

A new phenylethanoid glycoside, 2-(3,4-dihydroxyphenyl)-ethyl-O-alpha-L-rhamnopyranosyl-(1 --> 3)-O-alpha-L-rhamnopyranosyl-(1 --> 6)-4-O-E-feruloyl-beta-D-glucopyranoside (3-O-methyl poliu-moside, 1) along with five known phenylethanoid glycosides (2-6) were isolated from the aerial parts of Leucas indica Linn. The structure of compound 1 has been elucidated on the basis of spectral data. Compounds 1-6 exhibited significant antioxidant activity in 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical assay method. These compounds were also found to be moderate inhibitors of xanthine oxidase (XO) enzyme.     

Atropisomeric myristinins: selective COX-2 inhibitors and antifungal agents from Myristica cinnamomea

The first naturally occurring atropisomeric flavans, myristinins B (2), C (2a), E (4), and F (4a), together with their corresponding trans-isomers, myristinins A (1) and D (3), were isolated from the CH(2)Cl(2) extract of Myristica cinnamomea fruits. Compounds 1, the mixture of 2 and 2a, and the mixture of 4 and 4a, exhibited antifungal activity against Candida albicans with IC(50) values ranging from 5.9 to 8.8 microg/mL, and they selectively inhibited the enzyme cyclooxygenase-2 (COX-2).     

A new sesquiterpenoid from the rhizomes of Homalomena sagittifolia

A new sesquiterpenoid, 1α,4β,7β-eudesmanetriol (1), was isolated together with the known compounds 1β,4β,7β-eudesmanetriol (2) and oplopanone (3) from the rhizomes of Homalomena sagittifolia. The structures of these compounds were determined by extensive spectral analyses. The compounds 1 and 2 inhibited growth of Pseudomonas stutzeri with a MIC value of 117 μM when evaluated for antibacterial activity using the minimum concentration assay. Both these compounds showed remarkable activities against acetylcholinesterase enzyme with IC(50) values ranging between 25 and 26 μM. The isolation of these sesquiterpenoids and their biological activities observed in this study support the reported traditional uses of H. sagittifolia for the treatment of microbial related diseases and central nervous system disorders.     

New acetylcholinesterase inhibitors isolated from Delphinium uncinatum

The inhibition of acetylcholinesterase (AChE), the key enzyme in the breakdown of acetylcholine, is presently the most common pharmacological approach available for Alzheimer’s disease (AD). Despite research on the molecular bases of AD, potent therapeutic agent against its expansion is still needed. In searching for natural cholinesterase inhibitors, the present study was focused on the isolation of three new norditerpenoid alkaloids, uncinatine B-D together with known virescenine from Delphinium uncinatum. Chemical structures for all the isolated norditerpenoids (1–4) were established using latest spectroscopic techniques. The isolated undescribed compounds along with known virescenine were testified for their acetylcholinesterase inhibitory activity supported by docking analyses. Molecular docking simulation showed that the isolated compounds (1–4) were observed to adhered in the active site of AChE with docking scores ? 13.5322 (1), ?11.8173 (2), ?12.4240 (3) and ? 8.9352 (4) respectively. Overall results demonstrated that these natural norditerpenoids compounds were found as selective inhibitors of AChE. This is the first report regarding the use of bioactive ingredients of Delphinium uncinatum in testing against Alzheimer's disease.     

PTP1B Inhibitory Secondary Metabolites from an Antarctic Fungal Strain Acremonium sp. SF-7394

Chemical investigation of the Antarctic lichen-derived fungal strain Acremonium sp. SF-7394 yielded a new amphilectane-type diterpene, acrepseudoterin (1), and a new acorane-type sesquiterpene glycoside, isocordycepoloside A (2). In addition, three known fungal metabolites, (−)-ternatin (3), [D-Leu]-ternatin (4), and pseurotin A (5), were isolated from the EtOAc extract of the fungal strain. Their structures were mainly elucidated by analyzing their NMR and MS data. The absolute configuration of 1 was proposed by electronic circular dichroism calculations, and the absolute configuration of the sugar unit in 2 was determined by a chemical method. The inhibitory effects of the isolated compounds on protein tyrosine phosphatase 1B (PTP1B) were evaluated by enzymatic assays; results indicated that acrepseudoterin (1) and [D-Leu]-ternatin (4) dose-dependently inhibited the enzyme activity with IC₅₀ values of 22.8 ± 1.1 μM and 14.8 ± 0.3 μM, respectively. Moreover, compound 1 was identified as a competitive inhibitor of PTP1B.     

Synthesis the Analog of Strictosidine and Vincoside from Geniposide

Strictosidine (1), a well-known monoterpene indole alkaloid glycoside^[1,2], is the precursor and building stone of nearly 2200 indole and related alkaloids and was first isolated by G. N. Smith from Rhazya^[3]. It is constructed in vivo from secologanin (2) and tryptamine (3) by plant species^[1], as well as in vitro in the presence of the enzyme strictosidine synthase, or under biomimetic conditions in aqueous solution at pH 4.5 (Scheme 1). In the coupling reaction, a new chiral center is formed with complete stereoselectivity in the presence of the enzyme, or together with vincoside (4) in a 1:1 ratio in the absence of the enzyme. Here we describe the preparation of the analog of strictosidine and vincoside from geniposide via the biomimetic conditions. 7 and 8 can be used as the starting material to synthesize other analogs of indole and related alkaloids.     

A new monoterpenoid glycoside from Myrica esculenta and the inhibition of angiotensin I-converting enzyme

One new monoterpenoid glycoside, myresculoside (1), and eleven known compounds, were isolated from methanol extract of Myrica esculenta leaves by repeated column chromatography. The effects of these compounds on angiotensin I-converting enzyme (ACE) inhibition were investigated. Compounds 3 and 4 showed the most potent ACE inhibition with rates of 29.97% and 25.63% at concentration of 100 μM, respectively. Compounds 5, 6, and 11 showed weak activity with inhibitory rates of 0.07-1.41% at concentration of 100 μM.     

Novel bromotyrosine alkaloids: inhibitors of mycothiol S-conjugate amidase

[structure: see text] The novel alkaloids 1 and 4 were isolated from an Australian non-verongid sponge, Oceanapia sp. Compound 1 contains an unprecedented imidazolyl-quinolinone substructure attached to a bromotyrosine-derived spiro-isoxazoline. Three other known alkaloids were isolated in addition to 1 and 4 and together represent the first examples of inhibitors of a new mycobacterial enzyme mycothiol S-conjugate amidase (MCA).     

Lipoxygenase inhibiting ethyl substituted glycoside from Symplocos racemosa

Phytochemical investigation of Symplocos racemosa resulted in the isolation of a new ethyl substituted glycoside, 1-ethyl brachiose-3'-acetate (1) along with four known compounds ketochaulmoogric acid (2), nonaeicosanol (3), triacontyl palmitate (4) and methyl triacontanoate (5). The substitution of ethyl group on 1 was natural because during the course of extraction and purification ethanol was not used. The structural elucidation of the isolated compounds was based primarily on 1D- and 2D-NMR analysis, including COSY, HMQC, and HMBC correlations. The glycoside 1 and triacontyl palmitate (4) displayed the inhibitory potential against lipoxygenase and urease enzyme, respectively.     

Tyrosinase inhibitory and antileishmanial constituents from the rhizomes of Paris polyphylla

The search for bioactive natural products from the rhizomes of Paris polyphylla (Trilliaceae) has resulted in the isolation of four known constituents, 1,5-dihydroxy-7-methoxy-3-methylanthraquinone (1), diosgenin-3-O-[alpha-L-rhamnopyranosyl-(1 --> 3)-beta-D-glucopyranoside] (2), diosgenin-3-O-[alpha-L-rhamnopyranosyl-(1(Rha) --> 2(Glu))-alpha-L-arabinofuranosyl-(1(Ara) --> 4(Glu))]-beta-D-glucopyranoside (3), and diosgenin-3-O-[alpha-L-rhamnopyranosyl-(1(Rha) --> 2(Glu))-alpha-L-rhamnopyranosyl-(1(Ara) --> 4(Glu))]-beta-D-glucopyranoside (4). Their structures were identified by spectral comparison with the reported data. Compound 1 was isolated for the first time from this genus. The chloroform, ethyl acetate, and butanol extracts of the plant were found to have mild to moderate inhibitory potentials against the enzyme tyrosinase. Compound 1 showed strong (IC(50) = 0.23 microM), while compounds 2-4 and hydrolyzed product 4a showed mild to moderate (IC(50) = 0.93-36.87 microM) activities against the tyrosinase. Similarly, compounds 2-4 and 4a showed mild to moderate (IC(50) = 1.59-83.72 microg mL(-1)) antileishmanial activities.