Chemotaxonomic implications of the absence of sesquiterpene lactones in Grazielia multifida (DC.) R.M.King & H.Rob. (Asteraceae)

The phytochemical investigation of Grazielia multifida aerial parts yielded eight compounds, including four ent-kaurenic acid diterpenes derivatives, 15-tiglinoyloxy-ent-kaur-16-en-19-oic acid (1), 15-hydroxy-ent-kaur-16-en-19-oic acid (2), 17-hydroxy-ent-kaur-15-en-19-oic acid (3) and 15-isovaleroyloxy-ent-kaur-16-en-19-oic acid (4), one amino acid, tryptophan (5), and three flavonoids, eupafolin (6), guaijaverin (7) and quercitrin (8). The structures of the isolated compounds were established based on analysis of their spectroscopic data and comparison with literature. All the compounds were isolated from this species for the first time. The chemotaxonomic significance of the absence of sesquiterpene lactones in G. multifida has also been summarized.     

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.     

Microbial transformation of isosteviol oxime and the inhibitory effects on NF-κB and AP-1 activation in LPS-stimulated macrophages

Microbial transformation of isosteviol oxime (ent-16-E-hydroxyiminobeyeran-19-oic acid) (2) with Aspergillus niger BCRC 32720 and Absidia pseudocylindrospora ATCC 24169 yielded several compounds. In addition to bioconverting the d-ring to lactone and lactam moieties, 4α-carboxy-13α-hydroxy-13,16-seco-ent-19-norbeyeran-16-oic acid 13,16-lactone (7) and 4α-carboxy-13α-amino-13,16-seco-ent-19-norbeyeran-16-oic acid 13,16-lactam (10), one known compound, ent-1β,7α-dihydroxy-16-oxo-beyeran-19-oic acid (6), and five new compounds, ent-7α-hydroxy-16-E-hydroxyiminobeyeran-19-oic acid (3), ent-1β,7α-dihydroxy-16-E-hydroxyiminobeyeran-19-oic acid (4), ent-1β-hydroxy-16-E-hydroxyiminobeyeran-19-oic acid (5), ent-8β-cyanomethyl-13-methyl-12-podocarpen-19-oic acid (8), and ent-8β-cyanomethyl-13-methyl-13-podocarpen-19-oic acid (9), were isolated from the microbial transformation of 2. Elucidation of the structures of these isolated compounds was primarily based on 1D and 2D NMR, and HRESIMS data, and 3–5 were further confirmed by X-ray crystallographic analyses. Additionally, the inhibitory effects of all of these compounds were evaluated on NF-κB and AP-1 activation in LPS-stimulated RAW 264.7 macrophages. Among the compounds tested, 5 and 10 significantly inhibited NF-κB activation, with 5 showing equal potency to dexamethasone; 3 and 6–9 significantly inhibited AP-1 activation, particularly 8, which showed more inhibitory activity than dexamethasone.     

Bibenzyl and phenolic glycosides from Pterospermum heterophyllum

A new bibenzyl, heterophyllic acid (1), and three new phenolic glycosides, heterophylloside A–C (2–4), along with two known phenolic glycosides oldhamioside (5) and 6′-O-vanilloylisotachioside (6) were isolated from Pterospermum heterophyllum. The structures of these compounds were elucidated on the basis of 1D, 2D NMR, MS spectroscopic analysis, and chemical methods. Their cytotoxic activities against KB and MCF-7 cancer cell lines were evaluated. Compound 2 showed significant cytotoxic activities.     

Bioactivity-guided isolation of chemical constituents against H2O2-induced neurotoxicity on PC12 from Cimicifuga dahurica (Turcz.) Maxim.

Three new compounds (1, 6, 9), with six known compounds (2–5, 7–8) were obtained from water-soluble extract of Cimicifuga dahurica (Turcz.) Maxim. by bioactivity-guided isolation. Their structures were elucidated by chemical and spectral analysis, including 1D, 2D NMR data and HRESIMS. H₂O₂-induced neurotoxicity on PC12 cells model were conducted to evaluate the neuro-protective capability of these compounds. The piscidic acid derivatives compounds 4–7 showed marked neuro-protective effect at certain concentration.     

Cytotoxic terpenoids from Nardophyllum bryoides

The investigation of the ethanol extract of fresh aerial parts of the Patagonian shrub Nardophyllum bryoides collected in the province of Chubut, Argentina, yielded eleven terpenoids. These include: three seco-ent-halimane diterpenoids (1–3), two ent-halimanes (4–5) and six pentacyclic oleanane and ursane triterpenoids (6–11). Four of these compounds (2, 6, 8 and 11) are hitherto unknown, while two others (1 and 4) have been previously reported but only as synthetic products. Several of these compounds showed moderate cytotoxicity against a human pancreatic adenocarcinoma cell line while compounds 4 and 5 were active at micromolar concentrations. The main component, seco-chiliolidic acid (1), could be isolated from this extract in large amounts, turning N. bryoides into a sustainable source of this bioactive compound.     

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.     

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.     

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.     

Mannic acid,a new ent-kaurane dimer diterpenoid and other chemical constituents from different parts of Diospyros mannii

A new dimeric ent-kaurane diterpene, mannic acid (1), and 19 known compounds were isolated from the methanol extract of the stems, roots and leaves of Diospyros mannii Hiern (Ebenaceae). Their structures were established by NMR and MS data. This is the first report of asperglaucide from the family Ebenaceae, while mannic acid (1) and xylopic acid (2) are the first ent-kaurane diterpenes isolated from this family. Their chemotaxonomic value is discussed.     

β-Resorcylic acid derivatives with α-glucosidase inhibitory activity from Lasiodiplodia sp. ZJ-HQ1, an endophytic fungus in the medicinal plant Acanthus ilicifolius

Three new β-resorcylic acid derivatives, compounds 1–3, along with six known analogues (4–9) were isolated from an endophytic fungus Lasiodiplodia sp. ZJ-HQ₁ derived from medicinal plant Acanthus ilicifolius. Their structures were elucidated by 1D and 2D NMR spectroscopic analysis, high resolution mass spectrometric (HREIMS) data, and X-ray crystallography. The absolute configurations of compounds 1 and 2 were determined by the modified Mosher’s method. Compounds 1–7 showed more potent inhibitory effects against α-glucosidase activity than the clinical α-glucosidase inhibitor acarbose.     

Two new ent-kaurane diterpenoids from the leaves of Sphagneticola trilobata

Two new ent-kaurane diterpenoids, namely 3α,16α-dihydroxy-ent-kauran-19-oic acid (1) and 3α,9β-dihydroxy-ent-kauran-19-oic acid (2), together with eight known compounds were isolated and identified from the leaves of Sphagneticola trilobata. Their structures were elucidated on the basis of extensive spectroscopic analysis including 1D, 2D NMR and MS techniques. Known compounds 4, 5 and 8−10 were obtained from S. trilobata for the first time. These compounds were tested for their in vitro α-glucosidase inhibitory activity and their tyrosinase inhibitory potential. Compounds 2, 3 and 6 were found to show in vitro α-glucosidase inhibitory activity with IC₅₀ values ranging from 0.398 to 0.476 mM, which were close or more potent than reference compound acarbose (IC₅₀ 0.410 mM). Compounds 2 and 6 were further revealed to show in vitro tyrosinase inhibitory activity (IC₅₀ 29.25 and 40.74 μM) but inferior to that of the positive control kojic acid (IC₅₀ 12.55 μM).     

Polyoxygenated seco-cyclohexenes and other constituents from Uvaria valderramensis

Phytochemical study on the Philippine endemic Annonaceae plant Uvaria valderramensis afforded a new highly oxygenated seco-cyclohexene derivative, valderepoxide (1), along with the six known compounds uvamalols D (2) and G (3), grandiuvarone (4), 2′-hydroxy-3′,4′,6′-trimethoxychalcone (5), valderramenol B (6) and benzoic acid. The structure of 1 was determined through extensive spectroscopic analyses including 1D, 2D NMR and HRESIMS. Its relative stereochemistry was established using 2D-NOESY. This is the first report on the isolation of polyoxygenated compounds 1–3 and chalcone 5 from U. valderramensis.     

New alkamide and ent-kaurane diterpenoid derivatives from Senecio erechtitoides (Asteraceae)

Fractionation of a MeOH/CH₂Cl₂ (1/1) extract of the aerial parts of Senecio erechtitoides led to the isolation of six compounds including the hitherto unknown N-phenethylamide derivative named N-(p-hydroxyphenethyl)pentacosanamide (1), and a kauranoid derivative named derivative named ent-7-oxo-16α,17-dihydroxykauran-19-oic acid (2), as well as four known compounds, ent-Kaur-16-en-19-oic acid (3), ent-7β-hydroxykaur-16-en-19-oic acid (4), ent-7-oxokaur-16-en-19-oic acid (5), steppogenin 4′-O-β-d-glucoside (6). Their structures and relative configurations were elucidated on the basis of spectroscopic methods, chemical reactions, and comparison with previously known analogs. All isolates were evaluated for their antimicrobial activity and only diterpenoids were found to possess a potent inhibitor effect against the range of microorganism.     

Nitric oxide inhibitory constituents from Siegesbeckia pubescens

Two new sesquiterpenoids (1 and 2) and a new ent-pimarane type diterpenoid (3), together with eighteen known compounds (4–21), were isolated from the whole plants of Siegesbeckia pubescens. The structures of the new compounds were determined on the basis of 1D-, 2D NMR and HRESIMS data. All compounds were evaluated for their inhibitory effects on LPS-induced nitric oxide production in RAW 264.7 macrophages. Of these, highly oxygenated germacrane type sesquiterpenoids (1–2 and 13–14) showed significant inhibitory effects with IC₅₀ values ranging from 3.9 to 16.8 μM.     

Two new ent-kaurane diterpenoids from Wedelia trilobata (L.) Hitchc

Two new ent-kaurane diterpenoids, 16α,17,19-trihydroxy-18-nor-ent-kauran-4β-ol (1) and 17-chloro-16β-hydroxy-ent-kauran-19-oic acid (2) were isolated from the whole plant of Wedelia trilobata, together with five known ones (3–7). Their structures were elucidated on the basis of extensive spectroscopic analyses, including NMR and MS techniques. Compound 1 is an 18-nor-ent-kaurane type diterpenoid which is rare in nature, and compound 2 is the first chlorine-containing ent-kaurane diterpenoid so far isolated from plant family of Asteraceae. Known compound 4 was obtained from the genus Wedelia for the first time. Compounds 4–6 selectively showed in vitro antibacterial activity against three assayed Gram-(+) bacteria, especially 5 and 6 which showed the antibacterial activity against Staphylococcus aureus with MIC values (3.125–6.25 μg/mL) comparable to reference compound Kanamycin (MIC 3.125 μg/mL). Compounds 4–6 further displayed significant antibacterial activity against Gram-(−) bacterium Shigella dysenteriae with MIC value 3.125–12.5 μg/mL.     

Phytochemical study on the leaves of Wollemia nobilis

In this work, a phytochemical study performed on the leaves of the rare species, Wollemia nobilis W.G. Jones, K.D. Hill & J.M. Allen, is reported. By means of classical column chromatography and NMR Spectroscopy and Mass Spectrometry, nine compounds were evidenced. These were: pheophorbide a (1), isocupressic acid (2), acetyl-isocupressic acid (3), sandaracopimaric acid (4), agathic acid (5), 7–4′-4‴-tri-O-methyl-agathisflavone (6), 7–4′-7″-4‴-tetra-O-methyl-agathisflavone (7), caffeic acid (8) and shikimic acid (9). Compared to our previous phytochemical analysis on the male cones, some further compounds were identified i.e. compounds 1, 5, 6, 7 and 8. This confirmed the previous chemotaxonomic considerations of the species but also added new ones which were discussed within the text. In addition, a possible different accumulation of secondary metabolites in the tissues and organs of this plant was even noticed.     

Two new cryptoporic acid derivatives from the fruiting bodies of Cryptoporus volvatus

Two new cryptoporic acid derivatives, cryptoporic acid R (1) and 6′,6‴-cryptoporic acid G dimethyl ester (2), together with two known compounds, cryptoporic acid E (3) and cryptoporic acid E pentamethyl ester (4), were isolated from a 90% alcohol extract of the fruiting bodies of Cryptoporus volvatus. Their structures were established on the basis of NMR spectroscopic and mass spectrometry data. Cryptoporic acid E (3) and cryptoporic acid E pentamethyl ester (4) exhibited antiviral activity against porcine reproductive and respiratory syndrome virus.     

Two new quinic acid derivatives from the fruits of Chaenomeles speciosa

Two new quinic acid derivatives (1, 2), together containing eighteen (3–20) known compounds, were isolated from the fruits of Chaenomeles speciosa. Spectroscopic methods and previous data retrieved from the literature were used to determine the chemical structures of the compounds. Among the compounds, quinic acid derivatives (3, 4, 6, 7), phenolic acid compounds (8, 10, 11) and catechin derivatives (18, 19, 20) were isolated for the first time from the family Chaenomeles. The chemotaxonomic significance of the compounds was also discussed.