Isolation and characterization of three pairs of indolediketopiperazine enantiomers containing infrequent N-methoxy substitution from the marine algal-derived endophytic fungus Acrostalagmus luteoalbus TK-43

Three pairs of new N-methoxy-containing indolediketopiperazine enantiomers, acrozines A–C (1–3), were isolated from the culture extract of Acrostalagmus luteoalbus TK-43, an endophytic fungus obtained from the marine green alga Codium fragile. The optical resolution of compounds 1–3 by chiral HPLC successfully afforded individual enantiomers (+)-1/(–)-1, (+)-2/(–)-2, and (+)-3/(–)-3, respectively. The structures of all these compounds were established on the basis of detailed interpretation of their NMR and mass spectroscopic data. X-ray crystallographic analysis confirmed the structures of compounds 1–3, while the absolute configurations were determined by TDDFT-ECD calculations. All these compounds containing a N-methoxy group which is uncommon in indolediketopiperazines. The enantiomers, (+)-2/(–)-2, showed different antimicrobial activities against several plant-pathogenic fungi, while (+)-1 displayed better inhibitory activity against acetylcholinesterase than that of (–)-1.     

Oxirapentyns B–D produced by a marine sediment-derived fungus Isaria felina (DC.) Fr

Three new highly oxygenated chromene derivatives, oxirapentyns B–D (1–3) and one known oxirapentyn A (4) were isolated from the lipophilic extract of the marine-derived fungus Isaria felina KMM 4639. The structures of compounds 1–3 were determined based on spectroscopic methods. The absolute configuration of oxirapentyn B (1) as 2R, 4S, 5S, 6S, 7R, 8S, 9S was established by a combination of modified Mosher's method, X-ray analysis, and NOESY data. Oxirapentyn A (4) showed weak cytotoxicity against SK-Mel-5, SK-Mel-28 human malignant melanoma, and T-47D human breast cancer cell lines.     

Chemical constituents of Gardneria ovata wall

A phytochemical investigation on the aerial parts of Gardneria ovata Wall resulted in the isolation and identification of 14 compounds, including three gardneria glycoalkaloids (1–2 and 6), seven gardneria alkaloids (3–5 and 7–10), and four oxindole alkaloids (11–14). The structure of compound 1 was elucidated by means of spectroscopic analysis, including HRESIMS together with 1D and 2D NMR experiments. Compounds 1–2 and 11–14 are the first time reported from of G. ovate, while the compounds 3–4, 6, and 8 are also the characteristic secondary metabolites of the title plant. The chemotaxonomic significance and distribution of these monoterpenoid indole alkaloids in Gardneria genus are discussed.     

Polyketides from the marine mangrove-derived fungus Aspergillus ochraceus MA-15 and their activity against aquatic pathogenic bacteria

Three new polyketides, namely, asperochrins A–C (1–3), along with 12 known related derivatives (4–15), were isolated from Aspergillus ochraceus MA-15, a fungus obtained from the rhizospheric soil of marine mangrove plant Bruguiera gymnorrhiza. The structures of these compounds were elucidated on the basis of spectroscopic analysis and the absolute configurations of the new compounds were determined by CD experiments and modified Mosher's method. The X-ray crystallographic experiment of compound 4 disclosed its racemic nature as (±)-botryoisocoumarin A for the first time. The brine shrimp lethality and antibacterial activity of compounds 1–15 were evaluated. Compounds 1, 5, 6, 9, 11, and 15 showed inhibitory activity against aquatic pathogenic bacterial Aeromonas hydrophila, Vibrio anguillarum, and Vibrio harveyi.     

Design,synthesis and antimicrobial activities evaluation of Schiff base derived from secnidazole derivatives as potential FabH inhibitors

FabH, β-ketoacyl-acyl carrier protein (ACP) synthase III, is critically important to the initiation of fatty acid biosynthesis and is highly conserved among Gram-positive and Gram-negative bacteria. A series of novel secnidazole derivatives (1–20) were synthesized and fully characterized by spectroscopic methods and elemental analysis. Among these compounds, 6, 8, 11, 13, 14, 16–20 were reported for the first time. These compounds were tested for antibacterial activities against Escherichia coli, Pseudomonas aeruginosa, Bacillus subtilis and Staphylococcus aureus. The compounds inhibitory assay and docking simulation indicated that compound 20 (E)-2-(2-methyl-5-nitro-1H-imidazol-1-yl)-N′-(3,4,5-trimethylbenzylidene)acetohydrazide with MIC of 3.13–6.25 μg/mL against the tested bacterial strains was a potent inhibitor of Escherichia coli FabH.     

Synthesis,biological evaluation and molecular docking analysis of novel benzopyrimidinone derivatives as potential anti-tyrosinase agents

2-substitued-benzopyrimidinones 2 were synthesized in high to excellent yields in a single step via condensation of 2-aminobenzamide 1 with some aryl-aldehydes in the presence of iodine. Cyclocondensation reaction of hydrazides 3 which were obtained in two steps from benzopyrimidinones 2, with some electrophilic species such as 2,4-pentandione, 2,5-hexandione, 1-phenylbutan-1,3-dione and cyclic anyhdrides provided the new compounds 4a–c, 5a–c, 6a–c, 7a–c, 8a–c and 9a–c. The synthesized compounds were characterized by spectroscopic means. They were also evaluated for their anti-tyrosinase potential. The structure-activity relationship (SAR) was discussed on the basis of the molecular docking analysis.     

Phytochemical and chemotaxonomic study on Dianella ensifolia (L.) DC

Phytochemical investigation of the roots of Dianella ensifolia led to the isolation of eleven known compounds, including two aromatics (1, 2), two chromones (3, 4), and seven flavonoids (5–11). The structures of these compounds were elucidated on the basis of spectral analysis and comparison with data reported in literature. In the present research, all of the isolated compounds 1–11 were reported for the first time in the species D. ensifolia. Compounds 1–4 and 7–11 were firstly isolated from the genus Dianella. Compounds 1, 2, 8, and 9 have not been reported from any species in Liliaceae family. The chemotaxonomic significance of the isolated compounds was summarized.     

Flavonoid glycosides from the aerial parts of Curcuma comosa

Four new flavonoid glycosides, curcucomosides A–D (1–4), three known flavonoid glycosides, 5–7, and four known diarylheptanoids, 8–11, were isolated from the ethanol extract of the aerial parts of Curcuma comosa. The structures of the new compounds were established as rhamnazin 3-O-α-l-arabinopyranoside (1), rhamnocitrin 3-O-α-l-arabinopyranoside (2), rhamnazin 3-O-α-l-rhamnopyranosyl-(1→2)-O-α-l-arabinopyranoside (3), and rhamnocitrin 3-O-α-l-rhamnopyranosyl-(1→2)-O-α-l-arabinopyranoside (4) by spectroscopic analysis and chemical reactions whereas those of the known compounds were identified by spectral comparison with those of the reported values.     

Bioactive constituents of Morus wittiorum

From the stem bark of Morus wittiorum, one new Diels–Alder type adduct wittiorumin G (1) and three new 2-arylbenzofuran derivatives wittifurans P–R (2–4) along with five known Diels–Alder type adducts albafuran C, sorocein A, mulberrofuran E, mulberrofuran F and mulberrofuran O were isolated. Their structures were determined on the basis of spectroscopic analysis. Compounds 2–4 and two known compounds sorocein A and mulberrofuran F were evaluated for their antioxidant activity in a Fe²⁺/cysteine-induced microsomal lipid peroxidation assay and cytotoxicity against five human cancer cell lines respectively.     

Neuraminidase inhibitory activities of flavonols isolated from Rhodiola rosea roots and their in vitro anti-influenza viral activities

Five flavonols (3, 5, and 9–11) were isolated from Rhodiola rosea, and compared with commercially available flavonoids (1, 2, 4, 6–8, and 12–14) to facilitate analysis of their structure–activity relationship (SAR). All compounds (1–14) showed neuraminidase inhibitory activities with IC₅₀ values ranging from 0.8 to 56.9 μM. The in vitro anti-influenza virus activities of flavonoids 1–6, 8–12, and 14 were evaluated using two influenza viral strains, H1N1 (A/PR/8/34) and H9N2 (A/Chicken/Korea/MS96/96), testing their ability to reduce virus-induced cytopathic effect (CPE) in MDCK cells. We found that the activity of these compounds ranged from 30.2 to 99.1 μM against H1N1- and 18.5 to 133.6 μM against H9N2-induced CPE. Of compounds 1–14, gossypetin (6) exhibited the most potent inhibitory activity, with IC₅₀ values of 0.8 and 2.6 μM on neuraminidases from Clostridium perfringens and recombinant influenza virus A (rvH1N1), respectively. In contrast, kaempferol (3) exhibited the highest activity against two influenza viruses, H1N1 and H9N2 with EC₅₀ values of 30.2 and 18.5 μM, respectively. Activity depended on the position and number of hydroxy groups on the flavonoids backbone. In kinetic studies, all isolated compounds behaved as noncompetitive inhibitors.     

Chemical constituents from Anemone vitifolia Buch.-Ham. (Ranunculaceae)

A phytochemical investigation of Anemone vitifolia (Buch.-Ham.) led to the isolation of twelve compounds, including six lignans (1–6), four benzoic acid esters (7–10), one norsesquiterpenoid (11) and one lactone (12). The structures of these metabolites were established on the basis of detailed spectroscopic analysis, as well as comparisons with the data available in the literature. Among them, compounds 10 (dimethyl 2-(benzoyloxy)succinate) and 12 (4-hydroxy-5-methyl-γ-butyrolactone) were isolated for the first time as natural products. Compounds 1 and 11, compounds 2, 3, 5–7 and 9, and compounds 4 and 8 were isolated for the first time in family Ranunculaceae, genus Anemone and A. vitifolia respectively. The chemotaxonomic significance of the isolated compounds was discussed.     

Identification,characterization, kinetics,and molecular docking of flavonoid constituents from Archidendron clypearia (Jack.) Nielsen leaves and twigs

In our search for natural soluble epoxide hydrolase (sEH) inhibitors from plants, we found that the methanolic extract of the leaves and twigs of Archidendron clypearia (Jack.) Nielsen (Fabaceae) significantly inhibits sEH in vitro. In a phytochemical investigation of the water layer of A. clypearia, we isolated two new chalcones, clypesides A–B (1–2), 13 flavonoid derivatives (3–15) and established their structures based on an extensive 1D and 2D NMR, CD data, and MS analysis. All of the flavonoid derivatives inhibited sEH enzymatic activity in a dose-dependent manner, with IC₅₀ values ranging from 10.0 ± 0.4 to 30.1 ± 2.1 μM. A kinetic analysis of compounds 4, 8–10, 12, 13, and 15 revealed that the compounds 8–10 were non-competitive, 4, 13, and 15 were mixed-type, and 12 was competitive inhibitors. Additionally, molecular docking increased our understanding of their receptor-ligand binding. These results demonstrated that flavonoid derivatives from A. clypearia are potential sEH inhibitors.     

Chemical constituents of Melodinus hemsleyanus diels

Phytochemical investigation on the aerial parts of Melodinus hemsleyanus diels (Jahrb, Syst, 1995) led to the isolation and identification of 27 compounds, including fifteen aspidosperma-type alkaloids (1–15), four quinoline-type alkaloids (16–19), three quebrachamine-type alkaloids (20–22), and five eburna-type alkaloids (23–27). The structure of compound 1 was elucidated by means of spectroscopic analysis, including HRESIMS, and 1D and 2D NMR experiments. Compounds 1–2, 6, 10, 12, 13, 15, 16 and 20–27 are herein reported for the first time from the studied plant, while the compounds 1–2 and 21 have not previously been recorded in the genus Melodinus. The aspidosperma-type monoterpenoid indole alkaloids in M. hemsleyanus could serve as chemotaxonomic markers.     

Isolation of three new meroterpenoids and seven known compounds from Albatrellus yasudae and their Aβ-aggregation inhibitory activity

Alzheimer’s disease is a serious neurologic disorder that cannot be cured completely. In this study, we targeted compounds that inhibit amyloid-beta (Aβ) aggregation, based on the amyloid cascade hypothesis. Ten compounds (1–10) were isolated from CHCl₃ extracts of the mushroom Albatrellus yasudae using Aβ-aggregation inhibitory activity–guided separation. The structures of these compounds were elucidated from 1D and 2D NMR and MS spectral data. Compounds 1–3 were novel, whereas 4–10 were identified as the known compounds grifolin, grifolic acid, neogrifolin, confluentin, 2-hydroxyneogrifolin, daurichromenic acid, and a cerebroside derivative. Compounds 1–10 were tested for Aβ-aggregation inhibitory activity. Compounds 1, 3, 5, 6, 8, and 9 have potential as Aβ-aggregation inhibitory activity.     

Chemical constituents from bulbs of Fritillaria pallidiflora Schrenk

A new steroidal alkaloid, 5α, 14α, 17β-cevanin-6-oxo-3β, 20β, 24β-triol(1), together with ten known compounds (2–11) were isolated from the bulbs of Fritillaria pallidiflora Schrenk. Their structures were determined on the basis of spectroscopic analysis and by comparison of their spectral data with those reported in the literature. Compounds 8, 9, 10 were obtained from the genus Fritillaria for the first time; Compounds 2, 3, 4 and 11 are isolated from this plant for the first time.     

Flavonoids,megastigmanes and other constituents from Ardisia incarnata

Phytochemical investigation of the leaves and twigs of Ardisia incarnata Pit. (syn. Ardisia hanceana Mez, Primulaceae) led to the isolation of one bicyclic monoterpene (1), five phenolic compounds (2–5, 8), two megastigmanes (6–7) and one glyceroglycolipid (9). Their structures were established based on analysis of their spectroscopic data and comparison with literature. The compounds 1 and 6–9, isolated for the first time from Ardisia genus, may constitute chemomarkers of A. incarnata within Primulaceae family. Moreover, the flavonoid fingerprint may also be of chemotaxonomic significance.     

New diplosporin and agistatine derivatives produced by the fungal endophyte Xylaria sp. isolated from Vitis labrusca

A Xylaria sp. was isolated as an endophyte from a surface-sterilized Concord grape leaf (Vitis labrusca). Dereplication and LC–MS analysis of the filtrate extracts identified two new structures, compound 1, 13-O-methyl-(5R) diplosporin, and 2 a new agistatine. Additionally, five known compounds 3–7 including an agistatine, coriloxin, (5R)-diplosporin, and two mellein derivatives were also isolated. This is the first report of these structurally-related metabolites isolated from the same fungus, suggesting they share a related biosynthesis. Metabolites were isolated using liquid chromatography-solid phase extraction (LC-SPE) and semi-preparative HPLC. Structures were elucidated on the basis of 1D and 2D NMR analysis, HRMS measurements and X-ray structural analysis for compound 1.     

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.     

Nortriterpenoids from the roots of Paeonia emodi

Chemical investigation of chloroform–ethyl acetate extract from the roots of Paeonia emodi yielded four hitherto unknown noroleanane triterpenoids (1–4) together with four known compounds (5–8). Their structures were established by analysis of spectroscopic data. Compounds 1–8 were evaluated for cytotoxic activities against human cancer cell lines A549, HL-60, HCT116 and ZR-75-30. Compounds 1, 2, 3, 6 and 7 showed modest cytotoxicity against HL-60, HCT116 and ZR-75-30.     

Anthraquinone derivatives from Rumex plants and endophytic Aspergillus fumigatus and their effects on diabetic nephropathy

Two new oxanthrone C-glycosides, patientosides A (14) and B (15), together with three known ones (11–13), were isolated from Rumex patientia. Their structures were identified on the basis of spectroscopic methods. The absolute configuration for 14 and 15 were deduced by analysis of their CD spectra and comparison with those of known similar compounds. Compounds 11–15, and 14 known anthraquinones (1–4, 6–10, 16–20) previously isolated from Rumex nepalensis, Rumex hastatus, and endophytic Aspergillus fumigatus, respectively, as well as a commercially available compound rhein (5) were evaluated for their inhibitory effects on IL-6 and extracellular matrix production in mesangial cells.