Antioxidant chalcone glycosides and flavanones from Maclura (Chlorophora) tinctoria

Four chalcone glycosides (1-4), including three new natural products, and three flavanones (5-7) were isolated from the methanol extract of stem bark of Maclura tinctoria. The new compounds have been characterized as 4'-O-beta-D-(2' '-p-coumaroyl)glucopyranosyl-4,2',3'-trihydroxychalcone (1), 4'-O-beta-D-(2' '-p-coumaroyl-6' '-acetyl)glucopyranosyl-4,2',3'-trihydroxychalcone (2), and 3'-(3-methyl-2-butenyl)-4'-O-beta-D-glucopyranosyl-4,2'-dihydroxychalcone (3); the known derivatives were elucidated as 4'-O-beta-D-(2' '-acetyl-6' '-cinnamoyl)glucopyranosyl-4,2',3'-trihydroxychalcone (4), eriodictyol 7-O-beta-D-glucopyranoside (5), naringenin (6), and naringenin 4'-O-beta-D-glucopyranoside (7). Their structures were determined by 1D and 2D NMR and ESIMS. The antioxidant activity of all the isolated compounds was determined by measuring free-radical-scavenging effects using two different assays, namely, the Trolox Equivalent Antioxidant Capacity (TEAC) assay and the coupled oxidation of beta-carotene and linoleic acid (autoxidation assay). The results showed that compound 3 was the most active in both antioxidant assays.     

Phytoecdysteroids from Ajuga macrosperma var. breviflora roots

Three new phytoecdysteroids, ajugacetalsterones C (1) and D (3) and breviflorasterone (2), were isolated from the roots of Ajuga macrosperma var. breviflora along with five known compounds, namely, 20-hydroxyecdysone, cyasterone, makisterone A, 20-hydroxyecdysone 3-acetate, and 20-hydroxyecdysone 2-acetate. The structures of 1-3 were elucidated on the basis of extensive 1D and 2D NMR spectroscopic studies. The new compounds possess acetal oxygen bridges between C-26 and C-20/C-22, or C-26/C-23, or a lactone bridge between C-26 and C-23.     

Ferruginenes A-C from Rhododendron ferrugineum and their cytotoxic evaluation

Three new compounds, ferruginenes A (1) and B (2) and a mixture of C-5'(R) and C-5'(S) ferruginene C (3) diastereomers, have been isolated from a cytotoxic chloroform-soluble fraction of the leaves of Rhododendron ferrugineum together with 12 known compounds. The structures of these new compounds were elucidated by analyses of NMR spectroscopic and mass spectrometric data. Compounds 1-3 were tested for their cytotoxicity against three human cancer cell lines, namely, HL-60, HeLa-S3, and MCF-7.     

Cytotoxic triterpenoids from Acridocarpus vivy from the Madagascar rain forest

Bioassay-guided fractionation of the cytotoxic MeOH extract obtained from Acridocarpus vivy led to the isolation of five new triterpenoids, acridocarpusic acids A-E (1-5); three known triterpenoids, moronic acid (6), ursolic acid, and oleanolic acid; and two known flavonoids, 4',5-dihydroxy-7-methoxyflavone and 4',5-dihydroxy-3',7-dimethoxyflavone. The structures of the new compounds 1-5 were established on the basis of extensive 1D and 2D NMR spectroscopic data interpretation. Compound 3 showed significant cytotoxic activity in the A2780 assay, with an IC50 value of 0.7 microg/mL.     

Minor iridoids from the roots of Valeriana wallichii

Four new iridoids, valeriotetrates B and C (1 and 2), 8-methylvalepotriate (3), and 1,5-dihydroxy-3,8-epoxyvalechlorine A (4), together with three known iridoids, were isolated from the roots of Valeriana wallichii. The structures of the new compounds were elucidated by analysis of 1D and 2D NMR and HRESIMS data. Compound 4 is an unusual iridoid bearing a C-10 chloro group and an oxo bridge connecting C-3 and C-8, resulting in a rigid skeleton.     

Antimicrobial isopropenyl-dihydrofuranoisoflavones from Crotalaria lachnophora

Two new isopropenyl-dihydrofuranoisoflavones exhibiting antimicrobial properties have been isolated along with eight known compounds from the Cameroonian medicinal plant Crotalaria lachnophora. The structures of the new compounds were elucidated by 1D and 2D NMR spectroscopy and high-resolution mass spectrometry as 7,2',4'-trihydroxy-5'-isopropenyl-4',5'-dihydrofurano[2',3':5,6]isoflavone (1) and 4,8-dihydroxy-2-isopropenyl-2,3-dihydro-5H-[1]benzofuro[2,3-b]furo[3,2-g]chromen-5-one (2). The CH(2)Cl(2)/MeOH (1:1) extract and the compounds isolated were subjected to in vitro antimicrobial assays against a panel of pathogenic microorganisms, including Gram-positive and Gram-negative bacteria and fungi. The new compounds, named lachnoisoflavones A (1) and B (2), showed moderate inhibitory activities against Escherichia coli and Klebsiella pneumoniae.     

Tripfordines A-C, sesquiterpene pyridine alkaloids from Tripterygium wilfordii, and structure anti-HIV activity relationships of Tripterygium alkaloids

Three new sesquiterpene pyridine alkaloids, tripfordines A-C (1-3), were isolated from an ethanolic extract of the roots of Tripterygium wilfordii, along with eight known pyridine alkaloids, and tested for in vitro cytotoxic and anti-HIV activity. The structures of the new compounds were established on the basis of spectroscopic data interpretation. Anti-HIV structure-activity relationships (SAR) for this compound type are proposed on the basis of the screening results from the newly isolated compounds and prior data of known sesquiterpene pyridine alkaloids. The position of a carboxyalkyl chain on the pyridine moiety was not critical since both 2'- and 4'-substituted compounds exhibited high anti-HIV activity (EC(50) 0.1 microg/mL). In contrast, a hydroxy group at C-8' (carboxypropyl side chain) or C-9' (carboxybutyl side chain) was found to affect anti-HIV activity.     

Isolation and characterization of minor analogues of silvestrol and other constituents from a large-scale re-collection of Aglaia foveolata

Two new minor silvestrol analogues [2'-episilvestrol (1) and 2',5'-diepisilvestrol (2)], together with a new 21-norbaccharane-type triterpene (3), two new 3,4-secodammarane triterpenes (4 and 5), and a new eudesmane sesquiterpene (6), as well as nine known compounds, were isolated from a large-scale re-collection of the CHCl(3)-soluble extract of the stem bark of Aglaia foveolata obtained in Kalimantan, Indonesia. The structures of the new compounds were established by interpretation of their spectroscopic data. All of the isolates were tested for cytotoxicity against HT-29 cells. The new silvestrol analogues, 1 and 2, were considerably less active as cytotoxic agents than silvestrol (7) and episilvestrol (5'-episilvestrol) (8) against this cell line, showing the importance of the configuration at C-2' in mediating such activity within this compound class. Several of the compounds isolated were also evaluated in a NF-κB (p65) inhibition assay.     

Four new flavones and a new isoflavone from Iris bungei

Four new irisflavones A-D (1-4) and irilin D (5) have been isolated from the underground parts of Iris bungei along with known isoflavones, irilins A-B (6-7) and tlatancuayin (8). The structures of the new compounds were determined using NMR and mass spectroscopic methods and were found to be 2',5,7-trihydroxy-3,6-dimethoxyflavone (1), 2',5-dihydroxy-3,6,7-trimethoxyflavone (2), 2',5,6'-trihydroxy-3,6,7-trimethoxyflavone (3), 3,3',5-trihydroxy-2',7-dimethoxyflavone (4), and 3',4',5,7-tetrahydroxy-6-methoxyisoflavone (5). The structures of irisflavones 1, 3, and 4 were confirmed by single-crystal X-ray diffraction studies.     

Bioactive constituents from Asparagus cochinchinensis

Bioassay-directed fractionation of the dried roots of Asparagus cochinchinensis led to the isolation of a new spirostanol saponin, asparacoside (1), two new C-27 spirosteroids, asparacosins A (2) and B (3), a new acetylenic derivative, 3' '-methoxyasparenydiol (4), and a new polyphenol, 3'-hydroxy-4'-methoxy-4'-dehydroxynyasol (6), as well as five known phenolic compounds, asparenydiol (5), nyasol (7), 3' '-methoxynyasol (8), 1,3-bis-di-p-hydroxyphenyl-4-penten-1-one (9), and trans-coniferyl alcohol (10). Compounds 1, 6, and 8 demonstrated moderate cytotoxicities in a panel comprised of KB, Col-2, LNCaP, Lu-1, and HUVEC cells, with IC(50) values ranging from 4 to 12 microg/mL. The structures were determined by spectroscopic and chemical methods.     

Benzyl derivatives with in vitro binding affinity for human opioid and cannabinoid receptors from the fungus Eurotium repens

Bioassay-guided fractionation of the fungus Eurotium repens resulted in the isolation of two new benzyl derivatives, (E)-2-(hept-1-enyl)-3-(hydroxymethyl)-5-(3-methylbut-2-enyl)benzene-1,4-diol (1) and (E)-4-(hept-1-enyl)-7-(3-methylbut-2-enyl)-2,3-dihydrobenzofuran-2,5-diol (2), along with seven known compounds (3-9) including five benzaldehyde compounds, flavoglaucin (3), tetrahydroauroglaucin (4), dihydroauroglaucin (5), auroglaucin (6), and 2-(2',3-epoxy-1',3'- heptadienyl)-6-hydroxy-5-(3-methyl-2-butenyl)benzaldehyde (7), one diketopiperazine alkaloid, echinulin (8), and 5,7-dihydroxy-4-methylphthalide (9). The chemical structures of these compounds were established on the basis of extensive 1D and 2D NMR and HRMS data. Compounds 1-4 and 6 showed good binding affinity for human opioid or cannabinoid receptors. These findings have important implications for psychoactive studies with this class of compounds.     

Alkaloids from the leaves of Uncaria rhynchophylla and their inhibitory activity on NO production in lipopolysaccharide-activated microglia

Two new isomeric alkaloids, 18,19-dehydrocorynoxinic acid B (1) and 18,19-dehydrocorynoxinic acid (2), were isolated from the CHCl3 extract of the leaves of Uncaria rhynchophylla, together with four known rhynchophylline-type alkaloids, corynoxeine (3), isocorynoxeine (4), rhynchophylline (5), and isorhynchophylline (6), and an indole alkaloid glucoside, vincoside lactam (7). The structures of compounds 1 and 2 were elucidated by spectroscopic methods including UV, IR, HREIMS, 1D and 2D NMR, and CD experiments. The activity assay showed that compounds 3-6, with a C-16 carboxylic ester group, and 7 exhibited inhibitory activity on lipopolysaccharide (LPS)-induced NO release in primary cultured rat cortical microglia (IC 50: 13.7-19.0 microM). However, only weak inhibitory activity was observed for compounds 1 and 2, with a C-16 carboxylic acid group (IC 50: >100 microM).     

Dimeric aporphine alkaloids of Phoenicanthus obliqua from Sri Lanka.

A new dimeric aporphine alkaloid, phoenicanthusine (1), and six known alkaloids were isolated from the stem bark of Phoenicanthus obliqua. The structure of 1 was elucidated by 1D ((1)H, (13)C) and 2D ((1)H-(1)H COSY, HMQC, HMBC, and NOESY) NMR and HRMS studies. Phoenicanthusine represents the first example of a N-6--C-4' and C-7--C-5' linked dimeric aporphine alkaloid.     

Acylated flavonol glycosides from the flower of Inula britannica

Three new acylated flavonol glycosides, patuletin 7-O-(6' '-isobutyryl)glucoside (1), patuletin 7-O-[6' '-(2-methylbutyryl)]glucoside (2), and patuletin 7-O-(6' '-isovaleryl)glucoside (3), were isolated from the n-BuOH extract of Inula britannica flowers by bioassay-guided fractionation, together with other known flavonoids. The structures were elucidated by 1D and 2D NMR, FABMS, and other spectral analyses. The eight flavonoids, including new compounds (1-3), patulitrin (7), nepitrin (8), axillarin (10), patuletin (11), and luteolin (12), showed profound antioxidant activity in DPPH assay and cytochrome-c reduction assay using HL-60 cell culture system.     

Diacarperoxides, norterpene cyclic peroxides from the sponge Diacarnus megaspinorhabdosa

Chemical investigation of the hexane extract of the sponge Diacarnus megaspinorhabdosa provided a series of new norterpene derivatives including three norditerpene cyclic peroxides, diacarperoxides A, B, and C (1 to 3), four norsesterterpene cyclic peroxides, diacarperoxides D to G (4 to 7), and the acyclic norsesterterpene diacardiol A (8). In addition, known norterpene peroxide congeners were also isolated, which included a known norsesterterpene cyclic peroxide (9), nuapapuin A methyl ester (10), epimuqubilin B (11), methyl-2-epinuapapuinoate (12), and methyl diacarnoate A (13). The structures of the new compounds were established on the basis of one- and two-dimensional NMR spectroscopic studies ((1)H, (13)C, COSY, HMQC, HMBC, and ROESY) as well as by mass spectrometric analyses. The relative configuration of chiral centers at C-2, C-3, and C-6 was assigned by established empirical rules. All compounds were evaluated for their cytotoxic properties in vitro using several human as well as murine cancer cell lines.     

New cytotoxic bis 5-alkylresorcinol derivatives from the leaves of Oncostemon bojerianum from the Madagascar rainforest

Bioassay-directed fractionation of a CH(2)Cl(2)-MeOH extract of the leaves of Oncostemon bojerianum resulted in the isolation of eight new 5-alkylresorcinols, named oncostemonols A-H (1-8), and two known derivatives, (8'Z)-1,3-dihydroxy-5-[16'-(3' ',5' '-dihydroxyphenyl)-8'-hexadecen-1'-yl]benzene (9) and (8'Z)-1,3-dihydroxy-5-[14'-(3' ',5' '-dihydroxyphenyl)-8'-tetradecen-1'-yl]benzene (10). The structures of the new compounds 1-8 were elucidated on the basis of extensive 1D and 2D NMR spectroscopic interpretation and chemical derivatization. All the compounds exhibited cytotoxic activity against the A2780 ovarian cancer cell line.     

Investigation of brominated tryptophan alkaloids from two thorectidae sponges: Thorectandra and Smenospongia

Chemical investigation of an NCI-DTP collection of Thorectandra sp. and a UCSC collection of Smenospongia sp. yielded six new brominated tryptophan derivatives: 6-bromo-1'-hydroxy-1',8-dihydroaplysinopsin (4), 6-bromo-1'-methoxy-1',8-dihydroaplysinopsin (5), 6-bromo-1'-ethoxy-1',8-dihydroaplysinopsin (6), (-)-5-bromo-N,N-dimethyltryptophan (7), (+)-5-bromohypaphorine (8), and 6-bromo-1H-indole-3-carboxylic acid methyl ester (11). Additionally, the known compounds aplysinopsin (1), 1',8-dihydroaplysinopsin (2), 6-bromo-1',8-dihydroaplysinopsin (3), (1H-indole-3-yl)acetic acid (9), and (6-bromo-1H-indol-3-yl)acetic acid methyl ester (10) were also encountered. The structures of 4-8 and 11 were confirmed on the basis of analysis of (1)H and (13)C (1D and 2D) NMR data as well as comparison to known compounds. Compounds 1, 3-8, 10, and 11 were found to inhibit the growth of Staphylococcus epidermidis with either weak or moderate MICs.     

Phytotoxic withanolides from Jaborosa rotacea

Twelve new withanolides were isolated from the aerial part of Jaborosa rotacea: five had a spiranoid delta-lactone (1-5); one contained a 26,12-delta-lactone and a C-12-C-23 bond (6); five corresponded to trechonolide-type withanolides with configuration at C-23 opposite of those previously isolated (7, 8, 10-12); two of these have an additional oxido-bridge between C-21 and C-24; finally a withanolide with a hemiketal ring formed between a 21-hydroxyl and a 12-ketone (13) and the closely related jaborosalactone R were also isolated. New compounds were fully characterized by a combination of spectroscopic methods (1D and 2D NMR and MS). The structures of the spiranoid withanolide and of the epimer of trechonolide A were confirmed by X-ray diffraction studies. Compounds 4, 5, 6, and 8 showed selective phytotoxicity toward monocotyledoneous and dicotyledoneous species.     

Neolignans, a coumarinolignan, lignan derivatives, and a chromene: anti-inflammatory constituents from Zanthoxylum avicennae

Eight new compounds, including four new neolignans, (7' S,8' S)-bilagrewin ( 1), (7' S,8' S)-5-demethoxybilagrewin ( 2), (7' S,8' S)-5- O-demethyl-4'- O-methylbilagrewin ( 3), and (7' S,8' S)-nocomtal ( 4), a new coumarinolignan, (7' S,8' S)-4'- O-methylcleomiscosin D ( 5), two new lignan derivatives, (+)-9'- O-( Z)-feruloyl-5,5'-dimethoxylariciresinol ( 6) and (+)-9'- O-( E)-feruloyl-5,5'-dimethoxylariciresinol ( 7), and a new chromene, ( E)-3-(2,2-dimethyl-2 H-chromen-6-yl)prop-2-enal ( 8), have been isolated from the stem wood of Zanthoxylum avicennae, together with 18 known compounds ( 9- 26). The structures of these new compounds were determined through spectroscopic and MS analyses. (7' S,8' S)-4'- O-Methylcleomiscosin D ( 5), cleomiscosin D ( 9), skimmianine ( 18), robustine ( 19), and integrifoliolin ( 23) exhibited inhibition (IC 50 < or = 18.19 microM) of superoxide anion generation by human neutrophils in response to formyl- l-methionyl- l-leucyl- l-phenylalanine/cytochalasin B (FMLP/CB). In addition, skimmianine ( 18) inhibited FMLP/CB-induced elastase release with an IC 50 value of 19.15 +/- 0.66 microM.     

Sesquiterpene esters of aristolochic acid from the root and stem of Aristolochia heterophylla

Three novel sesquiterpene esters of aristolochic acid, aristoloterpenate-II (2), -III (3), and-IV (4), together with known aristoloterpenate-I (1), were isolated and characterized from the root and stem of Aristolochia heterophylla. Their structures were elucidated by spectroscopic methods. The absolute configuration of these compounds at C-4' was determined as R by circular dichroic studies. These compounds showed cytotoxicity against hepatoma G2, 2, 2, 15 cells.