CsF�CCelite catalyzed facile N-alkylation of 2(3H)-benzoxazolones and antimicrobial properties of 2-substituted benzoxazole and 3-substituted-2(3H)-benzoxazolone derivatives

The synthesis and antimicrobial activity studies of a new series of cyclic amine containing benzoxazoles and benzoxazolone-2(3H)-ones derivatives were described. The alkylation of benzoxazolone was carried out using cesium fluoride–Celite. The newly synthesized compounds with the influence of the induction of the cyclic amine moiety in the benzoxazole scaffold have been evaluated with respect to the antibacterial and antifungal activity. The 2-cyclic amine-1,3-benzoxazoles (5a–l), 5-chloro-3-alkyl substituted-1,3-benzoxazol-2(3H)-ones (8a–f), and 3-[3-(cyclic amine)propyl]-1,3-benzoxazol-2(3H)-ones (9a–f) were synthesized. These derivatives were tested for antibacterial and antifungal activity. Among the compounds tested, 8c and 9f showed moderate to good antibacterial and antifungal activity. Compound 8a showed good antifungal activity.     

In Vitro Antibacterial and Antifungal Activities of Extracts and Compounds from Uvaria scheffleri

Petroleum ether, dichloromethane, and ethanolic extracts of the stem bark and leaves of Uvaria scheffleri Diels (Annonaceae) exhibited antifungal activity against Aspergillus niger (wild strain), Aspergillus fumigatus (wild strain), and a Penicillium species (wild strain). The ethanol extract of the stem bark was also active against Candida albicans (Strain H6392). The dichloromethane extract of the leaves showed the highest antifungal activity and in addition it showed antibacterial activity against Staphylococcus aureus (NCTC 6571). Fractionation of the dichloromethane extract of the leaves yielded nine known compounds. They included a 1 : 1 mixture of stigmasterol (1) and β-sitosterol (2), which showed antifungal activity against Candida albicans. Others were 3-farnesylindole (3), 2′,6′-dihydroxy-3′,4′-dimethoxy-chalcone (4), 2′-hydroxy-3′,4′,6′-trimethoxychalcone (5), 5-hydroxy-7,8-dimethoxyflavanone (6), 5,7,8-trimethoxyflavanone (7), and a 3 : 2 mixture of 2′,6′-dihydroxy-4′-methoxychalcone (8) and 5,7-dihydroxyflavone (9). Compound 7 and the mixture of compounds 8 and 9 showed antibacterial activity against Escherichia coli (NCTC 10418, MIC 125 µg/ml) and Staphylococcus aureus (MIC 125 µg/ml), respectively. The mixture of compounds 8 and 9 was also active against Candida albicans (MIC 31.25 µg/ml), Aspergillus niger, Aspergillus fumigatus, and the Penicillium species (MIC 1000 µg/ml). We conclude that Uvaria scheffleri extracts contain compounds with antifungal and antibacterial activity. The activities observed in this study are weak. Based on previous studies, it is being speculated that, possibly, the most active compounds were lost during fractionation. Further work to isolate more antifungal and antibacterial compounds is suggested.     

Free radical scavengers from the aerial parts of <Emphasis Type="Italic">Euphorbia petiolata</Emphasis>

Reversed-phase preparative high-performance liquid chromatography (HPLC) of the methanol extract of the aerial parts of Euphorbia petiolata Banks & Soland, an endemic Iranian medicinal plant, yielded ten free radical scavengers including eight flavonoid glycosides myricetin 3-O-glucoside (1), kaempferol 3-O-(2-O-galloyl)-glucoside (2), myricetin 3-O-rhamnoside (3), quercetin 3-O-glucoside (4), kaempferol 3-O-glucoside (5), quercetin 3-O-rhamnoside (6), kaempferol 3-O-rhamnoside (7), and quercetin 3-O-rutinoside (10), a coumarin esculetin (8) and a phenylpropanoid 2-hydroxydihydrocinnamic acid (9). The structures of these compounds were elucidated conclusively by spectroscopic means and also by direct comparison of their spectroscopic data with respective published data. The free radical scavenging properties of these compounds were assessed by the 2,2-diphenyl-1-picrylhydrazyl assay.     

Garcixanthone A,a new cytotoxic xanthone from the pericarps of Garcinia mangostana

A new prenylated xanthone, garcixanthone A (5), together with eight known compounds, mangostanaxanthones I (1) and II (2), garcinone E (3), β-mangostin (4), 8-hydroxycudraxanthone G (6), garcinone C (7), cudraxanthone G (8), and (-)-epicatechin (9) were isolated from the EtOAc-soluble fraction of the air-dried pericarps of Garcinia mangostana (family Clusiaceae). Their structures were verified on the basis of spectroscopic data interpretation as well as comparison with the literature. The cytotoxic and antimicrobial activities of the new compound were assessed using sulforhodamine B (SRB) and agar disk diffusion assays, respectively. Compound 5 showed significant cytotoxic potential against epithelial lung carcinoma (A549) and breast carcinoma (MCF7) cell lines with IC₅₀s 3.0 and 4.2 μM, respectively, compared to doxorubicin (0.74 and 0.41 μM, respectively).     

A new kaempferol trioside from <Emphasis Type="Italic">Solidago altissima</Emphasis> L.

A new kaempferol trioside [kaempferol 3-O-rutinoside 7-O-β-d-apiofuranoside, (1)] was isolated together with nine phenolic compounds, trans-tiliroside (2), caffeic acid (3), chlorogenic acid (4), 3-O-caffeoylquinic acid (5), 4-O-caffeoylquinic acid (6), 3-O-coumaroylquinic acid (7), 4-O-coumaroylquinic acid (8), 3,5-di-O-caffeoylquinic acid (9) and 4,5-dicaffeoylquinic acid (10) from the leaves of Solidago altissima L. The structure elucidations of the compounds were based on the analyses of spectroscopic data.     

A new auronol from Cudrania cochinchinensis

A new auronol, cudrauronol (1), was isolated from the roots of Cudrania cochinchinensis along with 10 known compounds, 1,3,5-trihydroxy-4-prenylxanthone (2), 1,3,7-trihydroxy-4-prenylxanthone (3), 3,4′,5,7-tetrahydroxydihydroflavonol (4), kaempferol (5), 3,6-dihydroxy-1,5-dimethoxyxanthone (6), 2′,4′,5,7-tetrahydroxyflavanolol (7), 3,7-dihydroxy-1-methoxyxanthone (8), 1,3,5-trihydroxyxanthone (9), cudraflavone B (10), and 2′-oxyresveratrol (11). Compounds 1–8 were evaluated for anti-inflammatory activity on lipopolysaccharide-induced nitric oxide production in RAW 264.7 macrophages. Compounds 2–5 were more active than aminoguanidine, with IC₅₀ values of 8.8, 23.2, 27.1, and 11.9 μM, respectively.     

Antimicrobial and antioxidant effects of phenolic constituents from Klainedoxa gabonensis

Bioassay-guided fractionation of the methanol extract of the stem bark of Klainedoxa gabonensis Pierre ex Engl. (Irvingiaceae) afforded 12 compounds, namely, ellagic acid (1), ellagic acid 3,3′-dimethylether (2), gallic acid (3), methyl gallate (4), lupeol (5), β-amyrin (7), erythrodiol (8), oleanolic acid (9), betulinic acid (6), hederagenin (10), bayogenin acid (11), and stigmasterol-3-O-β-d-glucopyranoside (12). Compounds 1-3 and 7-12 were isolated for the first time from this genus. The structures were established on the basis of 1D/2D NMR experiments and mass spectrometric data. Crude extract, fractions (A, B, C and D) and pure compounds were tested for their antimicrobial activity using paper disk agar diffusion assay. The test delivered a range of low to high activities for phenolic compounds 1-4, low or missing activities for terpenoid compounds 5-11, and impressive very high antibacterial/antifungal values for two fractions C and D probably due to synergistic effects of compounds. The broth microdilution assay revealed MICs of 15.4-115.1?μg/mL for phenolic compounds, MICs higher than 1?mg/mL for terpenoids and MICs of 4.5-30.3?μg/mL for fractions C and D. The determination of the radical scavenging activity using 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay gave high antioxidant values for the methanol extract and fraction D (IC₅₀ 10.45 and 5.50?μg/mL) as well as for the phenolic compounds 1-4 (IC₅₀ 45.50-48.25?mM) compared to the standard 3-t-butyl-4-hydroxyanisole (BHA) (IC₅₀ 44.20?mM).     

PTP1B inhibitors from Ardisia japonica

In bioassay-directed isolation from the whole plant of Ardisia japonica, sixteen known compounds: chrysophanol (1), physcion (2), oleanolic acid (3), euscaphic acid (4), tormentic acid (5), quercetin (6), quercitrin (7), myricitrin (8), kaempferol 3-O-α-l-rhamnopyranoside (9), cyclamiretin A 3-O-α-l-rhamnopyranosyl(1→4)-β-d-glucopyranosyl(1→2)-[β-d-glucopyranosyl(1→4)]-α-l-arabinopyranoside (10), (7E)-9-hydroxymegastigma-4, 7-dien-3-on-9-O-β-d-glucopyranoside (11), bergenin (12), norbergenin (13), rutin (14), kaempferol 3,7-O-α-l-dirhamnopyranoside (15), (?)-epigallacatechin 3-O-gallate (16) were obtained. Compounds 1–5, 9, 11 and 14–16 have not been reported previously from this plant. Among these isolates, 2, 3, 6 and 12 showed moderate bioactivity against PTP1B in vitro with IC₅₀ values of 121.50, 23.90, 28.12 and 157?μM, respectively.     

Cytotoxic phenolic compounds from <Emphasis Type="Italic">Chionanthus retusus</Emphasis>

Cytotoxicity-guided fractionation and purification of MeOH extract from Chionanthus retusus Lindl. et Paxton resulted in the isolation of compounds. Fourteen phenolic compounds were isolated from the EtOAc soluble fraction, and their structures were determined by spectroscopic analysis. Isolated compounds were identified as phillygenin (1), scopoletin (2), pinoresinol (3), kaempferol (4), aromadendrin (5), 2-(4-hydroxyphenyl)ethanol (6), 3,3′,5,5′,7-pentahydroxyflavanone (7), luteolin (8), quercetin (9), apigenin (10), chrysoeriol (11), phillyrin (12), oleuropein (13), (7R,8R)-guaiacylglycerol (14). All compounds except for 12 and 13 were isolated for the first time from this plant and genus Chionanthus. Anti-proliferative effect of isolated compounds were evaluated by the sulforhodamin B assay against four human tumor cell lines (A549, SK-OV-3, SK-MEL-2, and HCT15). Compounds 4 and 8–10 were significantly active with ED50 values of 1.84–6.35 μg/mL. Also, compounds 1, 3, 5 and 7 revealed cytotoxic effects at concentrations below 30 μg/mL.     

Five new compounds from Dendrobium crystallinum

Five new compounds, dencryol A (1), dencryol B (2), crystalltone (3), crystallinin (4), and 3-hydroxy-2-methoxy-5,6-dimethylbenzoic acid (5), together with six known compounds, dendronobilin B (6), syringic acid (7), apigenin (8), isoviolanthin (9), 6?-glucosyl-vitexin (10), and palmarumycin JC2 (11), have been isolated from the stems of Dendrobium crystallinum, of which compounds 9–11 were isolated from the genus Dendrobium for the first time, and all the other compounds were first obtained from this plant. Their structures were established on the basis of spectroscopic analysis and literature data.     

Two new antioxidant diarylheptanoids from the fruits of Alpinia oxyphylla

Two new diarylheptanoids, 1-(3′,5′-dihydroxy-4′-methoxyphenyl)-7-phenyl-3-heptanone (1) and 1-(2′,4′-dihydroxy-3′-methoxyphenyl)-7-(4″-methoxyphenyl)-3-heptanone (2), along with known diarylheptanoid yakuchinone A (3), and five flavanoids, tectochrysin (4), chrysin (5), izalpinin (6), kaempferol 7, 4′-dimethyl ether (7), and kaempferide (8) were isolated from the fruits of Alpinia oxyphylla Miq. Their structures were determined by means of spectroscopic methods. Antioxidant activities of all the isolated compounds were evaluated using a 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay. Compounds 1–3 and 6–8 exhibited potent antioxidant activities in the DPPH assay.     

Isolation and characterization of secondary metabolites from Plumeria obtusa

Chromatographic purification of the methanolic extract of Plumeria obtusa yielded two new iridoid obtusadoids A (1) and B (2), along with eight known compounds plumieridin A (3), plumieridine (4), 1α-plumieride (5), 15-demethylplumieride (6), rel-(3R,3′S,4R,4′S)-3,3′,4,4′-tetrahydro-6,6′-dimethoxy[3,3′-bi-2H-benzopyran]-4,4′-diol (7), glochiflavanoside B (8), oleanolic acid (9), and methyl coumarate (10). The structures of all the isolates (1–10) were determined by NMR spectroscopy and mass spectrometry. The data of known compounds (3–10) were further compared with the reported data for these compounds.     

Phenolic constituents of <Emphasis Type="Italic">Acorus gramineus</Emphasis>

The purification of a MeOH extract from the rhizome of Acorus gramineus (Araceae) using column chromatography furnished two new stereoisomers of phenylpropanoid, acoraminol A (1) and acoraimol B (2). It also furnished 17 known phenolic compounds, β-asarone (3), asaraldehyde (4), isoacoramone (5), propioveratrone (6), (1′R,2′S)-1′,2′-dihydroxyasarone (7), (1′S,2′S)-1′,2′-dihydroxyasarone (8), 3′,4′-dimethoxycinnamyl alcohol (9), 3′,4′,5′-trimethoxycinnamyl alcohol (10), kaempferol 3-methyl ether (11), 2-[4-(3-hydroxypropyl)-2-methoxyphenoxy]-1,3-propanediol (12), hydroxytyrosol (13), tyrosol (14), (2S,5S)-diveratryl-(3R,4S)-dimethyltetrahydrofuran (15), (7S,8R)-dihydrodehydrodiconiferyl alcohol (16), 7S,8S-threo-4,7,9,9′-tetrahydroxy-3,3′-dimethoxy-8-O-4′-neolignan (17), 7S,8R-erythro-4,7,9,9′-tetrahydroxy-3,3′-dimethoxy-8-O-4′-neolignan (18), and dihydroyashsbushiketol (19). The structures of the new compounds were elucidated by analysis of spectroscopic data including 1D and 2D NMR data. The absolute configurations of 1 and 2 were determined using the convenient Mosher ester procedure. Compounds 5–19 were isolated for the first time from this plant source. The isolated compounds were tested for cytotoxicity against four human tumor cell lines in vitro using a Sulforhodamine B (SRB) bioassay.     

Two new sesquiterpene polyol esters from the root barks of Celastrus angulatus

Angulatin F (1) and angulatin I (2), two new sesquiterpene polyol esters, were isolated from the root barks of Celastrus angulatus, together with six known compounds 1β,2β-diacetoxy-4α,6α-dihydroxy-8α-isobutanoyloxy-9β-benzoyloxy-15-(α-methyl) butanoyloxy-β-dihydroagrofuran (3), angulatin A (4), angulatin B (5), celangulatin E (6), 1β,2β,15-triacetoxy-4α,6α-dihydroxy-8α-isobutanoyloxy-9β-benzoyloxy-β-dihydroagrofuran (7), and celangulin I (8). The structures of 1 and 2 were elucidated as 1β,2β,6α,15-tetraacetoxy-4α-hydroxy-8β,9α-difuroyloxy-β-dihydroagrofuran and 1β,2β,6α,8β,15-pentaacetoxy-4α-hydroxy-9β-furoyloxy-β-dihydroagrofuran by spectroscopic means.     

A new flavonol galloylrhamnoside and a new lignan glucoside from the leaves of <Emphasis Type="Italic">Koelreuteria henryi</Emphasis> Dummer

A new flavonol galloylrhamnoside, kaempferol 3-O-(2″,3″-di-O-galloyl)-α-l-rhamnopyranoside, and a new lignan glycoside, hinokinin 7-O-β-d-glucopyranoside were isolated from the leaves of Koelreuteria henryi, along with 18 known compounds, including six flavonol glycosides (3–8), three lignans (9–11), four chlorophyll derivatives (12–15), two steroids (16, 17), and three aromatic compounds (18–20). The structures were determined on the basis of spectral analysis and chemical evidence. The scavenging effect of 1–8 and 20 on the stable free radical 1,1-diphenyl-2-picrylhydrazyl was examined. Compounds 1, 5, 6, and 20 showed more potent activity than that of trolox.     

New prenylated flavones from <Emphasis Type="Italic">Artocarpus champeden</Emphasis>, and their antimalarial activity in vitro

Two new prenylated flavones, artocarpones A and B (1 and 2), and seven known isoprenylated flavonoids, artonin A (3), cycloheterophyllin (4), artoindonesianin E (5), artoindonesianin R (6), heterophyllin (7), heteroflavanone C (8), and artoindonesianin A-2 (9), have been isolated from the stem bark of Artocarpus champeden. Their structures were determined by spectroscopic analysis. Among the compounds isolated, 8 had the most potent inhibitory activity against the growth of Plasmodium falciparum 3D7 clone, with an IC₅₀ value of 1 nmol L⁻¹.     

In Vitro Antimicrobial Activity of Benzoquinolinediones

The in vitro antibacterial and anti-fungal activity of benz[g]isoquinoline-5,10-dione (1), benzo[g]quinoline-5, 10-dione (2), benzo[g]quinoline-5,6-dione (3), and anthraquinone (4) was determined using the agar well-diffusion assay. The minimum inhibitory concentrations (MIC's) of each of the active compounds (1–3) was determined using the two-fold serial dilution technique. Of the four compounds tested, benz[g]isoquinoline-5,10-dione exhibited the best overall activity against both bacteria and fungi. Particularly noteworthy was its significant antifungal activity which was comparable to the activity of the standard antifungal antibiotic amphotericin B.     

Potential anthelmintics: polyphenols from the tea plant <Emphasis Type="Italic">Camellia sinensis</Emphasis> L. are lethally toxic to <Emphasis Type="Italic">Caenorhabditis elegans</Emphasis>

A novel gallate of tannin, (−)-epigallocatechin-(2β→O→7′,4β→8′)-epicatechin-3′-O-gallate (8), together with (−)-epicatechin-3-O-gallate (4), (−)-epigallocatechin (5), (−)-epigallocatechin-3-O-gallate (6), and (+)-gallocatechin-(4α→8′)-epigallocatechin (7), were isolated from the tea plant Camellia sinensis (L.) O. Kuntze var. sinensis (cv., Yabukita). The structure of 8, including stereochemistry, was elucidated by spectroscopic methods and hydrolysis. The compounds, along with commercially available pyrogallol (1), (+)-catechin (2), and (−)-epicatechin (3), were examined for toxicity towards egg-bearing adults of Caenorhabditis elegans. The anthelmintic mebendazole (9) was used as a positive control. Neither 2 nor 3 were toxic but the other compounds were toxic in the descending order 8, 7 ≈ 6, 9, 4, 5, 1. The LC₅₀ (96 h) values of 8 and 9 were evaluated as 49 and 334 μmol L⁻¹, respectively. These data show that many green tea polyphenols may be potential anthelmintics.     

Aspergchromones A and B,two new polyketides from the marine sponge-associated fungus Aspergillus sp. SCSIO XWS03F03

Two new polyketides, aspergchromones A (1) and B (2), together with five known compounds, secalonic acid D (3), noreugenin (4), (3S)-5-hydroxymellein (5), (4S)-6-hydroxyisosclerone (6), and (-)-regiolone (7), were isolated from the ethyl acetate extract of marine sponge-derived fungus Aspergillus sp. SCSIO XWS03F03. Their structures were elucidated by means of spectroscopic techniques (1D and 2D NMR, MS, UV, and IR). The absolute configurations of the new compounds were established by ECD calculations. Compound 3 showed moderate antimicrobial activity.     

Protein tyrosine phosphatase 1B (PTP1B) inhibitory activity and glucosidase inhibitory activity of compounds isolated from Agrimonia pilosa

Context: Despite phytochemical studies of Agrimonia pilosa Ledeb. (Rosaceae), the antidiabetic effects of this plant are unknown.

Objective: This study characterizes the isolated compounds from the aerial parts of A. pilosa and evaluates their PTP1B and α-glucosidase inhibitory properties.

Materials and methods: Ethanol extract of A. pilosa was found to inhibit 64% PTP1B activity at 30?μg/mL. The ethanol extract was partitioned with methylene chloride, ethyl acetate, n-butanol, and water fractions. Among these, the ethyl acetate fraction displayed the most potent PTP1B activity. The ethyl acetate extract was separated by chromatographic methods to obtain flavonoids and triterpenoids (1–11); which were evaluated for their inhibitory effects on PTP1B activity with p-nitrophenyl phosphate (p-NPP) as a substrate, and also α-glucosidase enzyme.

Results: Compounds 1–11 were identified as apigenin-7-O-β-d-glucuronide-6″-methyl ester, triliroside, quercetin-7-O-β-d-glycoside, quercetin-3-O-β-d-glycoside, kaempferol, kaempferol-3-O-α-l-rhamnoside, β-sitosterol, ursolic acid, tormentic acid, methyl 2-hydroxyl tricosanoate, and palmitic acid. Compounds 8, 9, and 11 displayed inhibitory effects on PTP1B activity with IC₅₀ values of 3.47?±?0.02, 0.50?±?0.06, and 0.10?±?0.03?μM, respectively. Compounds 3, 4, 6, and 9 exhibited inhibition of the α-glucosidase activity with IC₅₀ values of 11.2?±?0.2, 29.6?±?0.9, 28.5?±?0.1, and 23.8?±?0.4?μM, respectively.

Discussion and conclusion: As major ingredients of A. pilosa, compounds 1, 6, 8, and 9 showed the greatest inhibitory potency on PTP1B activity. Compounds 3, 6, 8, and 9 also showed potent inhibitory effects on α-glucosidase enzyme. This result suggested the potential of these compounds for developing antidiabetic agents.