Microbial transformation of neoandrographolide by Mucor spinosus (AS 3.2450)

Microbial transformation of neoandrographolide (1), was performed by Mucor spinosus (AS 3.2450). Ten metabolites were obtained and identified as 14-deoxyandrographolide (2), 17,19-dihydroxy-8,13-ent-labdadien-16,15-olide (3), 3,14-dideoxyandrographolide (4), 7β-hydroxy-3,14-dideoxyandrographolide (5), 17,19-dihydroxy-7,13-ent-labdadien-16,15-olide (6), 8(17),13-ent-labdadien-16,15-olid-19-oic acid (7), 8α,17β-epoxy-3,14-dideoxyandrographolide (8), 8β,17,19-trihydroxy-ent-labd-13-en-16, 15-olide (9), phlogantholide-A (10), 19-[(β-d-glucopyranosyl)oxy]-19-oxo-ent-labda-8(17),13-dien-16,15-olide (11) by spectroscopic and chemical means. Among them, products 3, 5, 6, 8 and 9 were characterized as new compounds. The inhibitory effects of compounds 1–11 on nitric oxide production in lipopolysaccharide-activated macrophages were evaluated and their preliminary structure–activity relationships (SAR) were discussed.     

Bioactive constituents of Helianthus tuberosus (Jerusalem artichoke)

In a cytotoxicity-guided study using the MCF-7 human breast cancer cell line, nine known compounds, ent-17-oxokaur-15(16)-en-19-oic acid (1), ent-17-hydroxykaur-15(16)-en-19-oic acid (2), ent-15β-hydroxykaur-16(17)-en-19-oic acid methyl ester (3), ent-15-nor-14-oxolabda-8(17),12E-dien-18-oic acid (4), 4,15-isoatriplicolide angelate (5), 4,15-isoatriplicolide methylacrylate (6), (+)-pinoresinol (7), (?)-loliolide (8), and vanillin (9) were isolated from the chloroform-soluble subfraction of a methanol extract of the whole plant of Helianthus tuberosus collected in Ohio, USA. This is the first time that diterpenes have been isolated and identified from this economically important plant. The bioactivities of all isolates were evaluated using the MCF-7 human breast cancer cell line as well as a soybean isoflavonoid defense activation bioassay. The results showed that two germacrane-type sesquiterpene lactones, 5 and 6, are cytotoxic agents. While compounds 2, 3, 5 and 6 blocked isoflavone accumulation in the soybean, the norisoprenoid (?)-loliolide (8) was somewhat stimulatory of these defense metabolites.     

Phenolic constituents from the roots of Rosa laevigata (Rosaceae)

Chemical investigation of the root of Rosa laevigata led to the isolation of sixteen phenolic compounds, including seven flavonoids (1–7), five condensed tannins (8–12), two stilbenes (13 and 14) and two benzoic acid derivatives (15 and 16). Their structures were identified as (+)-catechin (1), (+)-gallocatechin (2), (2R, 3S, 4S)-cis- leucocyanidin (3), (2R, 3S, 4S)-cis-leucofisetinidin (4), (2S, 3R, 4R)-cis- leucofisetinidin (5), dehydrodicatechin A (6), phloridzin (7), procyanidin B3 (8), fisetinidol-(4α, 8)-catechin (9), guibourtinidol- (4α, 8)-catechin (10), ent- isetinidol -(4α, 6)-catechin (11), fisetinidol-(4β, 8)-catechin (12), (Z)-3-methoxy-5-hydroxy- stilbene (13), (Z)-piceid (14), gallic acid (15) and 4-hydroxybenzoic acid- 4-O-β-D-glucopyranoside (16). Among them, compounds 3–7, 9–14, and 16 were isolated from R. laevigata for the first time, and compounds 3–7, 9, 10, 12–14 and 16 were reported for the first time from the genus Rosa. The chemotaxonomic significance of these compounds was summarized.     

Phytochemical and chemotaxonomic study on Piper pleiocarpum Chang ex Tseng

The phytochemical study of Piper pleiocarpum Chang ex Tseng led to the isolation of eighteen compounds (1–18), including ten lignanoids, galbelgin (1), (+) sesamin (2), denudatin A (3), hancinone (4), (7S,8S, 3′R)-Δ^8'-3,3′,4-trimethoxy-3′,6′-dihydro-6′-oxo-7.0.4′,8.3′-lignan[(2S,3S,3aR)-2-(3,4-dimethoxyphenyl)-3,3a-dihydro-3a-methoxy-3-methyl-5-(2-propenyl)-6(2H))-benzofuranone] (5), (−)-(7R,8R)-machilin D (6), (1R,2R)-2-[2-methoxy-4-((E)-prop-1-enyl)phenoxy]-1-(3,4-dimethoxyphenyl)propyl acetate (7), piperbonin A (8), machilin D (9), 4-methoxymachilin D (10), one amide alkaloid, Δ^α,β-dihydropiperine (11), six polyoxygenated cyclohexenes, ent-curcuminol F (12), uvaribonol E (13), ellipeiopsol A (14), 1S,2R,3R,4S-1-ethoxy-2-[(benzoyloxy)methyl]cyclohex-5-ene-2,3,4-triol, 3-acetate (15), (+)-crotepoxide (16), (+)-senediol (17), and one benzoate derivative, 2-acetoxybenzyl benzoate (18). Their structures were established by spectroscopic data and by comparison with the literature. All the compounds were firstly isolated from P. pleiocarpum, while ten compounds 6–7, 9–10, 12–15, 17–18 were isolated from the genus Piper and the family Piperaceae for the first time. The chemotaxonomic significance of these compounds was also discussed. The isolation of compounds 6–7, 9–10 may be used as chemotaxonomic markers for the genus of Piper.     

Chemotaxonomic significance of lindenane sesquiterpenoid dimers and eudesmane sesquiterpenoids from Chloranthus henryi Hemsl. var. hupehensis (Pamp.) K. F. Wu

Seventeen known compounds were isolated from the 95% alcohol extract of the aerial parts of Chloranthus henryi Hemsl. var. hupehensis (Pamp.) K. F. Wu, including five lindenane sesquiterpenoid dimers (1–5) and twelve eudesmane sesquiterpenoids (6–17). In the present research, compounds 3 sarcaglabrin C, 6 neolitacumone C, 7 ent-Atractylenolide III and 8 dehydrocarissone were reported from the Chloranthus genus for the first time, and compounds 1 spicachlorantin B, 2 chloramultilide C, 4 shizukaol B, 5 japonicone C, 9 6α-hydroxyeudesma-4(15),7(11),8(9)-triene-12,8-olide, 10 ent-(3R)-3-hydroxyatractylenolide III, 11 8βH-hydroxyeudesma-4(14),7(11)-dien-12,8-olide, 12 lasianthuslactone A, 13 (5S,6R,8S,10R)-6-hydroxyeudesma-4(15),7(11)-diene-12,8-olide, 14 4β-hydroxy5α,8β(H)-eudesm-7(11)-en-8,12-olide, 15 4β,8β-dihydroxy-5α(H)-eudesm-7(11)-en-8,12-olide, 16 curcolonol and 17 1β, 8β-dihydroxyeudesm - 3,7(11)-dien-8α,12-olide were firstly isolated from the plant. Their structures were elucidated on the basis of extensive spectroscopic and chemical analyses. Moreover, the chemotaxonomic significance of the isolated compounds is discussed.     

Diterpenoids from the stems of Tripterygium hypoglaucum (Celastraceae) and cytotoxic evaluation

Four new diterpenoids, 2α,16α-hydroxy-ent-kauran-19,20-olide (1), isopimara-8(14),15-diene-11β,19-diol (2), isopimara-8(14),15-diene-12α,19-diol (3), and 3-oxo-14,15-dihydroxyabieta-8,11,13-trien-19-ol (4), along with seven known compounds (5–11) were isolated from Tripterygium hypoglaucum. Their structures were established on the basis of extensive spectroscopic analysis. Triptolide (5) and 2-epitripdiolide (6) showed significant cytotoxicity against A549, DU145, KB, KBvin and MDA-MB-231 cell lines with IC₅₀ values of 0.0012–0.1306 μM in vitro.     

Chemical constituents from Hovenia dulcis Thunb. And their chemotaxonomic significance

Phytochemical investigations on the fruit stalks and seeds of the plant Hovenia dulcis Thunb. led to the isolation of twenty-one compounds, including three triterpenes (1–3), two sterols (4–5), five flavonoids (6–10), two sesquiterpenes (11–12), one lignan (13), two phenylpropanoids (14–15), four benzoic acid derivatives (16–19), one acid amide (20) and one cerebroside (21). The structures of these compounds were elucidated on the basis of spectroscopic analysis and comparison with previous literatures. Among them, ten compounds (4, 11–12, 14–20) were isolated from familiy Rhamnaceae, two (13, 21) from the genus Hovenia, and three (5, 8, 10) from the species Hovenia dulcis Thunb. for the first time, respectively. The chemotaxonomic significance of these isolates was also discussed.     

Two new antioxidant flavones from the twigs of Eriosema robustum (Fabaceae)

Phytochemical study of the ethanol extract of the twigs of Eriosema robustum, a Cameroonian medicinal plant resulted to the isolation of two new flavones, 2′,3′,5′,5,7-pentahydroxy-3,4′-dimethoxyflavone (1) and 2′,3,5′,5,7-pentahydroxy-4′-methoxyflavone (2), along with five known compounds: 6-prenylpinocembrin (3), 1-O-heptatriacontanoyl glycerol (4), β-sitosterol (5), stigmasterol (6) and 3-O-β-d-glucopyranoside of sitosterol (7). The structure of the isolated compounds were elucidated on the basis of their NMR, UV and MS data, and by comparison with those reported in the literature. The ethanol crude extract, fractions and some isolated compounds (1–4) were evaluated for their radical scavenging capacity using 2,2-diphenyl-1-picryhydrazyl (DPPH). The crude extract, fraction II, the new compounds namely robusflavones A (1) and B (2) exhibited significant antioxidant activity.     

Zierane sesquiterpene lactone,cembrane and fusicoccane diterpenoids,from the Tahitian liverwort Chandonanthus hirtellus

Cembrane-type diterpenoids, 13,18,20-epi-iso-chandonanthone (1) and (8E)-4α-acetoxy-12α,13α-epoxycembra-1(15),8-diene (2), two fusicoccane-type diterpenoids, fusicoauritone 6α-methyl ether (3) and 6β,10β-epoxy-5β-hydroxyfusicocc-2-ene (4) and a zierane sesquiterpene γ-lactone, chandolide (5) were isolated from the Tahitian liverwort Chandonanthus hirtellus (Web.) Mitt., together with eight known diterpenoids, chandonanthine (6), fusicogigantone A (7), fusicogigantone B (8), fusicogigantepoxide (9), anadensin (10), fusicoauritone (11), ent-verticillol (12) and ent-epi-verticillol (13). Their structures were established by a combination of extensive NMR spectroscopy and/or X-ray crystallographic analyses. Compounds 1, 5 and 10 showed weak cytotoxic activity against HL-60. Compound 3 also indicated weak cytotoxic activity against KB cell lines.     

Renoprotective chemical constituents from an edible mushroom,Pleurotus cornucopiae in cisplatin-induced nephrotoxicity

Pleurotus cornucopiae (Pleurotaceae) is an edible and medicinal mushroom widely distributed in Korea, China, and Japan. The MeOH extract of the fruiting bodies of P. cornucopiae showed renoprotective effects against cisplatin-induced kidney cell damage. Chemical investigation of the MeOH extract led to the isolation and identification of 12 compounds including noransine (1), uridine (2), uracil (3), (3β, 5α, 6β, 22E, 24S) -ergosta-7, 22-diene-3, 5, 6, 9-tetrol (4), (22E,24S)-ergosta-7,22-diene-3β,5α,6β-triol (5), (22E,24R)-ergosta-8(14),22-diene-3β,5α,6β,7α-tetrol (6), cerebroside B (7), (2R) -N- [(1S, 2R, 3E, 7E) -1- [(β-d-glucopyranosyloxy) methyl] -2-hydroxy-8-methyl-3, 7-heptadecadien-1-yl] -2-hydroxy-heptadecanamide (8), cerebroside D (9), nicotinamide (10), 1,2-bis(hydroxymethyl)-4,5-dimethoxybenzene (11), and benzoic acid (12). Among them, compounds 1 and 11 were isolated as naturally occurring products for the first time, though they were reported as synthetic products in previous papers. All of the compounds (except 8 and 11) abrogated cisplatin-induced LLC-PK1 cell damage in a dose-dependent manner. Of special note, compounds 2, 5, 6, and 12 ameliorated cisplatin-induced nephrotoxicity to 80% of the control value at 10 μM. The protective effects of compounds 2, 5, 6, and 12 were mediated via the deactivation of JNK-caspase 3 apoptotic cascade. This study is the first to demonstrate that the chemical constituents of P. cornucopiae display renoprotective effects against anticancer drug-induced damage in kidney cells.     

Chemical constituents from the fruits of Rhus typhina L. and their chemotaxonomic significance

This work describes the isolation and characterization of twenty-nine compounds from the fruits of Rhus typhina L., including eleven flavonoids (1–11), eleven phenols (12–22), two pentacyclic triterpenes (23–24), two organic acids (25–26), one lumichrome (27), one courmarin (28) and one pyrimidine (29) on the basis of their spectroscopic data. Compounds apigenin (1), daidzein (4), orobol (5), 3′, 5, 5′, 7-tetrahydroxyflavanone (6), naringenin (7), butein (8), (-)-catechin (9), quercetin-3-O-α-L-(3″-O-galloyl)-rhamnoside (11), 2-hydroxybenzoic acid (13), 4-hydroxybenzaldehyde (14), vanillin (15), methyl 3,4-dihydroxybenzoate (16), 3,5-dihydroxybenzamide (18), tyrosol (19), caffeic acid (20), 3-(2,4,6-trihydroxyphenyl)-1-(4-hydroxyphenyl)-propan-1-one (21), phlorizin (22), friedelin (23), oleanolic acid (24), 4,4-dimethyl-heptanedioic acid (25), anthranilic acid (26), lumichrome (27), scoparone (28) and uracil (29) have not been recorded before in this plant. This is the first report on the occurrence of compounds 4–7, 9, 11, 13–14, 16, 18–21, 25–29 from the genus Rhus. Moreover, the chemotaxonomic significance of these isolated compounds was also summarized.     

Biotransformation of ent-pimaradienoic acid by cell cultures of Aspergillus niger

Microbial transformation stands out among the many possible semi-synthetic strategies employed to increase the variety of chemical structures that can be applied in the search for novel bioactive compounds. In this paper we obtained ent-pimaradienoic acid (1, PA, ent-pimara-8(14),15-dien-19-oic acid) derivatives by fungal biotransformation using Aspergillus niger strains. To assess the ability of such compounds to inhibit vascular smooth muscle contraction, we also investigated their spasmolytic effect, along with another five PA derivatives previously obtained in our laboratory, on aortic rings isolated from male Wistar rats. The microbial transformation experiments were conducted at 30 °C using submerged shaken liquid culture (120 rpm) for 10 days. One known compound, 7α-hydroxy ent-pimara-8(14),15-dien-19-oic acid (2), and three new derivatives, 1β-hydroxy ent-pimara-6,8(14),15-trien-19-oic acid (3), 1α,6β,14β-trihydroxy ent-pimara-7,15-dien-19-oic acid (4), and 1α,6β,7α,11α-tetrahydroxy ent-pimara-8(14),15-dien-19-oic acid (5), were isolated and identified on the basis of spectroscopic analyses and computational studies. The compounds obtained through biotransformation (2–5) did not display a significant antispasmodic activity (values ranging from 0% to 16.8% of inhibition); however the previously obtained diterpene, methyl 7α-hydroxy ent-pimara-8(14),15-dien-19-oate (8), showed to be very effective (82.5% of inhibition). In addition, our biological results highlight the importance to study the antispasmodic potential of a large number of novel diterpenes, to conduct further structure–activity relationship investigations.     

Alkaloid and coumarins from the green fruits of Aegle marmelos

Five (1–5) and 15 known compounds (6–20) were isolated from the acetone extract of the green fruits of Aegle marmelos. The structure of compounds 1–5, marmesiline (1), 6-(4-acetoxy-3-methyl-2-butenyl)-7-hydroxycoumarin (2), 6-(2-hydroxy-3-hydroxymethyl-3-butenyl)-7-hydroxycoumarin (3), marmelonine (4) and 8-hydroxysmyrindiol (5), were determined on the basis of spectroscopic analyses. Antifungal and antibacterial activities of selected compounds were also evaluated.     

Chemical constituents from the roots of Cichorium glandulosum Boiss. et Huet (Asteraceae)

A phytochemical investigation of the roots extract of Cichorium glandulosum led to the isolation and characterization of fourteen compounds, including five sesquiterpene lactones (1–5), five flavonoids (6–10), and four lignans (11–14). Their structures were determined by spectroscopic data analysis and comparison with the literatures. This is the first report of the crystal data of lactucopicrin (1). This is the first time to report the isolation of 6,8,11-epi-desacetylmatricarin (2), desacetylmatricarin (3), ixerisoslde C (4), magnodelavin (5), 2ʹ,4-dihydroxy-4ʹ-methoxy-6ʹ-O-β-glucopyranoside dihydrochalcone (6), (−)-evofolin B (7), isoquercitrin (8), myricetin 7-methyl-ether-3-O-glucoside (9), (+)-medioresinol (12), 4-O-methylcedrusin [2-(3ʹ,4ʹ-dimethoxyphenyl)-3-hydroxymethyl-2,3-dihydro-7-hydroxybenzofuran-5-propan-1-ol] (13), and (2R,3S)-samwirin A (14) from C. glandulosum. Among them, compounds 5, 9, 13, and 14 were obtained from Asteraceae family for the first time. The chemotaxonomic significance of all the isolates 1–14 was discussed.     

New hexalactone derivatives and a pair of new oxaspiro-carbon epimeric glycosides from the fruits of Illicium lanceolatum

Five new compounds (1–5), including three hexalactone derivatives (1–3) and a pair of new oxaspiro-carbon epimeric glycosides (4 and 5), and six known compounds (6–11) were obtained from the fruits of Illicium lanceolatum. The structures of the new compounds were elucidated using extensive spectroscopic data. The absolute configurations of compounds 1–3 were determined by an analysis of their CD spectra. It was determined that compounds 4 and 5, which are epimeric at C-5, possess the same 1-oxaspiro[4,5]decane-7α,8α,9β-triol moiety. Plausible biogenetic pathways for 4 and 5 derived from the key precursor shikimic acid were proposed. Compounds 1–11 were all assayed on monosodium glutamate-induced human neuroblastoma SH-SY5Y cell damage. The results demonstrated that compounds 4, 5, and 8–10 possess potential neuroprotective effects. The anti-inflammatory, antiviral, and cytotoxic activities of 1–11 were also evaluated.     

Ultraviolet-induced amides and casbene diterpenoids from rice leaves

To discover new phytoalexins, an 80% MeOH extract of UV-irradiated rice leaves was analyzed using LC–MS, resulting in the detection of three unidentified compounds. We isolated the compounds from the UV-irradiated rice leaves using chromatographic methods and identified the compounds as N-benzoyltyramine (1), and two casbene-type diterpenes, 5-dihydro-ent-10-oxodepresssin (2) and 5-deoxo-ent-10-oxodepressin (3), using spectroscopic methods. Additionally, we compared the accumulation levels of major UV-inducible compounds in response to Magnaporthe oryzae inoculation and the antifungal activities of the compounds against M. oryzae colony growth. Although 1–3 showed negligible antifungal activity against M. oryzae, the compounds significantly accumulated in M. oryzae-inoculated rice leaves. Furthermore, we confirmed that N-benzoyltryptamine and N-cinnamoyltryptamine also accumulated after M. oryzae inoculation and have relatively high antifungal activity against M. oryzae to the same extent as phytocassanes. These results strongly support the hypothesis that the two amides are rice phytoalexins.     

Triterpenoids from the seedpods of Holarrhena curtisii King and Gamble

Two new hydroperoxy pentacyclic triterpenoids, 3β-hydroxy-11α-hydroperoxyolean-12-en-28-oic acid (1) and 3β-hydroxy-11α-hydroperoxyursan-12-en-28-oic acid (2), together with nine known triterpenoids, squalene (3), β-amyrin acetate (4), α-amyrin acetate (5), lupeol acetate (6), lupeol (7), lanosta-7,24-dien-3β-ol (8), cycloeucalenol (9), oleanolic acid (11) and ursolic acid (12), a known phytosterol, 24-methylenepollinastanol (10), and two known flavanols, (–)-catechin (13) and (–)-gallocatechin (14), were isolated from the methanolic extract of the fresh seedpods of Holarrhena curtisii. Their structures were determined by spectroscopic analysis (one and two dimensional nuclear magnetic resonance, high resolution electrospray ionization mass spectrometry and attenuated total reflectance-Fourier transform infrared spectroscopy). All compounds (except squalene) were evaluated for their in vitro α-glucosidase inhibitory activity. Compounds 1, 2, 11 and 12, which had a pentacyclic triterpenoid acid skeleton, showed a strong in vitro α-glucosidase inhibitory activity compared to that of the standard control, acarbose.     

Phytochemical and chemotaxonomic studies on the stems and leaves of Schisandra chinensis (Turcz.) Baill

A comprehensive phytochemical investigation of the stems and leaves of Schisandra chinensis (Turcz.) Baill. resulted in isolation of seventeen compounds, including five lignans: meso-dihydroguaiaretic acid (1), licarin-A (2), pregomisin (3), gomisin A (4), acutissimanide (5), three phenylpropanoids: 2-[4-(3-hydroxypropyl)-2-methoxyphenoxy]-propane-1,3-diol (6), 2-methoxy-4-(2-propenyl) phenyl β-D-glucopyranoside (7), erigeside 2 (8), six sesquiterpenoids: 7′-hydroxy-abscisic acid (9), burmannic acid (10), (3S,5R,6R,7E)-3,5,6-trihydroxy-7-megastigmen-9-one (11), 3-Cyclohexene-1,2-diol, 4-(3-hydroxybutyl)- 3, 5, 5-trimethyl- (12), (−)-loliolide (13), (3Z,5R,8R,11R)-Caryophyll-3-ene-5,8,15-triol (14), one monoterpenoid: (6R,3Z)-6,7-dihydroxy-3,7-dimethyl-2-octenoic acid (15) and two other compounds: methyl shikimate (16), 4-Hydroxydodec-2-enedioic acid (17). Their chemical structures were confirmed through NMR, HRESIMS and comparison with the data in the literature. This is the first report of compounds 5, 6, 8–15, 17 from the family Schisandraceae and compounds 2, 16 from the genus Schisandra. Furthermore, we performed a chemotaxonomic study of the separated compounds.     

NO inhibitory diterpenoids as potential anti-inflammatory agents from Euphorbia antiquorum

Two new ent-atisane-type diterpenoids (1 and 2), three new lathyrane-type diterpenoids (3–5), and seven known analogues (6–12) were isolated from Euphorbia antiquorum. The structures of these diterpenoids were established by analysis of their NMR, MS, and electronic circular dichroism data. The anti-inflammatory activities were evaluated biologically and compounds 1, 4, 7, 8, and 10 displayed strong NO inhibitory effects with IC₅₀ values less than 40 μM. The potential anti-inflammatory mechanism was also investigated using molecular docking and Western blotting.     

Chemotaxonomic significance of lignans from Serissa japonica (Thunb.) Thunb

Sixteen known lignans were isolated from the 95% alcohol extract of the whole plant of Serissa japonica (Thunb.) Thunb., including nine furofurans (1–9), three tetrahydrofurans (10–12) and four arylnaphthalenes (13–16). In the present report, compounds (+)-epipinoresinol (1), (+)-1-hydroxy-6-epipinoresinol 4,4″-di-O-methyl ether (3), (−)-pinoresinol (4), (+)-8-hydroxypinoresinol (6), pseuderesinol (7), (+)-1-hydroxysyringaresinol (8), (−)-(7′S,8S,8′R)-4,4′-dihydroxy-3,3′,5,5′-tetramethoxy-7′,9-epoxylignan-9′-ol-7-one (10), wikstrone (11), 7'-(+)-oxomatairesinol (12), (+)-cycloolivil (13), (+)-isolariciresinol (14), 5-methoxy-(+)-isolariciresinol (15) and cyclolignans (16) were reported from the Serissa genus for the first time, and compounds (+)-lirioresinol A (2) and (−)-lirioresinol B (5) were firstly isolated from the plant. Their structures were elucidated on the basis of extensive spectroscopic and chemical analyses. Moreover, the chemotaxonomic significance of the isolated compounds is discussed.