Two ambuic acid dimers derived from homo-endo Diels-Alder reaction from Pestalotiopsis versicolor.

Two new dimers of ambuic acid, pestaloversicoloric acids A (1) and B (2), and a known derivative, 13(S)-hydroxyambuic acid (3), were isolated from the static fermentation product of Pestalotiopsis versicolor. The structural identification was accomplished via analyses on the data of HR-MS, 1 D and 2 D NMR, and ECD. Different from the well-known exo-type dimer, torreyanic acid, compounds 1 and 2 represent the first example of endo-type product derived from the intermolecular Diels-Alder reaction of two molecules of ambuic acid derivative with the identical absolute stereochemistry.

[Isoquinoline alkaloids from two species of Thalictrum genus plants].

The chemical constituents from the roots of Thalictrum cultratum and T. baicalense were investigated. By various isolation methods, such as silica gel, aluminium oxide, ODS, and Sephadex LH-20 column chromatographies, and semi-preparative HPLC, 11 simple isoquinoline alkaloids were isolated from the ethanol extract of the roots of these two plants, including a new compound, named dehydrothalflavine(1), and ten known ones(2-11): N-methylcorydaline(2), N-methylthalidaldine(3), thaliflavine(4), oxyhydrastinine(5), noroxyhydrastinine(6), dimethoxyisoquinolone(7), thalactamine(8), dehydronoroxyhydrastinine(9), 6,7-dimethoxy-2-methyl-1,2,3,4-tetrahydroisoquinoline(10), and isopicnarrhine(11). Their structures were elucidated on the basis of HR-ESI-MS and 1 D and 2 D NMR techniques. Compound 1 was a new isoquinoline alkaloid. Compound 11 was obtained from Tha-lictrum plant for the first time. All compounds did not show cytotoxic activities against HL-60, U937, HCT116, Caco-2, and HepG2 cancer cell lines.

Polyprenylated xanthones from the twigs and leaves of Garcinia nujiangensis and their cytotoxic evaluation.

Inspired by the intriguing structures and bioactivities of polyprenylated xanthones, ten previously undescribed polyprenylated xanthones, nujiangxanthones G-P (1-10), and fifteen known ones (11-25) were isolated from the twigs and leaves of Garcinia nujiangensis. The structures of these compounds were established on the basis of spectroscopic data as well as comparison with the literature. Most of the isolates showed potent cytotoxicity against selected cancer cells. Compound 8 showed the highest effects against MDA-MB-231 and A549 cell lines with IC50 values of 4.12 and 2.67 µM and 16 demonstrated the most potent activity against MCF-7 cell line with an IC50 value of 3.36 µM.

Three new polyketides from Ascotricha sp. ZJ-M-5 by the OSMAC strategy.

Three new compounds, ascotrichols A-B (1-2) and ascotrichrone A (3), along with two known isocoumarin derivatives (4-5), were isolated from the solid culture of a sea mud-derived fungus, Ascotricha sp. ZJ-M-5 on rice media. The structures were elucidated by extensive spectroscopic analyses, including 1D and 2D NMR data, and the absolute configurations were determined by electronic circular dichroism and biogenetic correlation.

Polyketides from Pestalotiopsis zonata and structure revision of pestalrones A and B.

The structures of pestalrones A-B were revised via reinterpretation of the NMR data and a brief chemical transformation from the co-occurring polyketides, in our investigation on the secondary metabolites of Pestalotiopsis zonata, which also afforded a new α-pyrone derivative, pestazonatic acid, and four known analogs.

Cytotoxic quinazoline alkaloids from the seeds of Peganum harmala.

Seventeen quinazoline alkaloids and derivatives, containing two pairs of new epimers, named as (S)- and (R)-1-(2-aminobenzyl)-3-hydroxypyrrolidin-2-one ß-d-glucopyranosyl-(1 → 6)-ß-d-glucopyranoside (1, 2), (S)- and (R)-vasicinone ß-d-glucopyranosyl-(1 → 6)-ß-d-glucopyranoside (3, 4), and a new enantiomer (12b), together with six known ones (5-8, 10, and 12a), and three pairs of known enantiomers (9, 11, and 13), were isolated from the ethanol extracts of the seeds of Peganum harmala L.. Their structures including the absolute configuration were elucidated by using 1D and 2D NMR, and ECD calculation approaches. The cytotoxic activities of all isolated compounds were evaluated. 11 showed moderate cytotoxicity against PC-3 cells with an IC50 value of 15.41 µM.

Bioassay- and Chemistry-Guided Isolation of Scalemic Caged Prenylxanthones from the Leaves of Garcinia bracteata.

With bioassay- and chemistry-guided fractionation, seven new caged prenylxanthones including two scalemic mixtures, epiisobractatin (1), 13-hydroxyisobractatin (2), 13-hydroxyepiisobractatin (3), 8-methoxy-8,8a-dihydrobractatin (4), 8-ethoxy-8,8a-dihydrobractatin (5), garcibracteatone (6), and 8-methoxy-8,8a-dihydroneobractiatin (7), and the eight known compounds 8-15 were isolated from the leaves of Garcinia bracteata. The structures were unambiguously elucidated through analysis of spectroscopic data. The 2D structures and relative configurations of 1 and 5 were confirmed by X-ray crystallographic analysis. The separation of the enantiomers of 1-5 was accomplished by chiral-phase HPLC. The absolute configurations of the enantiomers of 1 and 5 were assigned by comparison of the experimental and calculated electronic circular dichroism (ECD) spectra. The absolute configurations of the related compounds were determined via comparisons of their ECD data with those of the enantiomers of 1 and 5, respectively. Notably, compound 7, with a neo caged skeleton, is the first representative of a novel type of caged xanthone lacking a Δ8(8a) double bond. The isolated compounds exhibited significant cell growth inhibitory activities in vitro against human leukemic HL-60 and K562 cell lines, with GI50 values ranging from 0.2 to 8.8 µM. A preliminary structure-activity relationship is discussed.

Bioactive terpenoids from Silybum marianum and their suppression on NO release in LPS-induced BV-2 cells and interaction with iNOS.

Three new (1-3) and one known (4) bioactive terpenoids were isolated from the seeds of Silybum marianum based on the investigation to get new NO inhibitors. Their structures were determined by extensive NMR (1D and 2D NMR) and MS spectroscopic data, and the absolute configurations were identified by experimental and calculated ECD spectra. The NO inhibitory activities in murine microglial BV-2 cells and interactions with iNOS protein by molecular docking were evaluated for all compounds. The results showed that these compounds had potent NO inhibitory effects.

Neobraclactones A-C, three unprecedented chaise longue-shaped xanthones from Garcinia bracteata.

Neobraclactones A-C (1-3), featuring an unprecedented further rearranged prenylxanthone skeleton with a unique octahydro-2H-1,3-dioxacyclopenta[c,d]inden-2-one scaffold, along with their biosynthesis-related known compound neobractatin (4), were isolated from the leaves of Garcinia bracteata. Their structures with absolute configurations were determined by extensive analyses of spectroscopic data and ECD calculations. Compounds 1 and 2 showed significant growth inhibition activities against the human leukaemia HL-60 and K562 cell lines with GI50 values from 0.40 to 0.86 µM.

Structurally Diverse Alkaloids from the Seeds of Peganum harmala.

Investigation of the alkaloids from Peganum harmala seeds yielded two pairs of unique racemic pyrroloindole alkaloids, (±)-peganines A-B (1-2); two rare thiazole derivatives, peganumals A-B (3-4); six new ß-carboline alkaloids, pegaharmines F-K (5-10); and 12 known analogues. Their structures, including stereochemistry, were elucidated through spectroscopic analyses, quantum chemistry calculations, and single-crystal X-ray diffraction. Notably, the incorporation of pyrrole and indole moieties in peganines A-B, thiazole fragments in peganumals A-B, and a C-1 α,ß-unsaturated ester motif in pegaharmine F (5) are all rare, and their presence in the genus Peganum were demonstrated for the first time. All isolates were tested for antiproliferative activities against the HL-60, PC-3, and SGC-7901 cancer cell lines, and compounds 9, 11, 12, and 13 exhibited moderate cytotoxicity against HL-60 cancer cell lines with IC50 values in the range of 4.36-9.25 µM.

Antiproliferative Dimeric Aporphinoid Alkaloids from the Roots of Thalictrum cultratum.

Inspired by the intriguing structures and bioactivities of dimeric alkaloids, 11 new thalifaberine-type aporphine-benzylisoquinoline alkaloids, thalicultratines A-K, a tetrahydroprotoberberine-aporphine alkaloid, thalicultratine L, and five known ones were isolated from the roots of Thalictrum cultratum. Their structures were defined on the basis of NMR and HRESIMS data. The antiproliferative activities of compounds 1-17 were evaluated against human leukemia HL-60 and prostate cancer PC-3 cells. Most alkaloids showed potent cytotoxicity against selected cancer cells. Preliminary SARs are discussed. The most active new compound (3), with an IC50 value of 1.06 µM against HL-60 cells, was selected for mechanism of action studies. The results revealed that compound 3 induced apoptosis and arrested the HL-60 cell cycle at the S phase with the loss of mitochondria membrane potential. The nuclear morphological Hoechst 33258 staining assay was also carried out, and the results confirmed apoptosis.

Two new threitol orsellinates from a sea mud-derived fungus, Ascotricha sp. ZJ-M-5.

Two new d-threitol orsellinates (1-2) were isolated from the EtOAc extract of a sea mud-derived fungus, Ascotricha sp. ZJ-M-5, cultured in Czapek Dox broth. These two compounds featured in the symmetrical substitution of orsellinic acid or acetic acid, which was established on the basis of 1D and 2D NMR experiments. The characteristic optical rotations enabled the assignment of the absolute configuration.

ent-Abietane-type diterpenoids from the roots of Euphorbia ebracteolata with their inhibitory activities on LPS-induced NO production in RAW 264.7 macrophages.

Ten ent-abietane diterpenoids (1-10), including four new (1-4) and six known ones (5-10) were isolated from the roots of Euphorbia ebracteolata. Their structures were determined by 1D, 2D NMR, and HRESIMS. Compounds 2, 4, and 7 exhibited significant inhibitory activities on lipopolysaccharide (LPS)-induced nitric oxide production in RAW 264.7 macrophages with IC50 values of 0.69, 1.97, and 0.88µM, respectively. A primary structure-activity relationship was also discussed.

Antiproliferative activity and apoptosis inducing effects of nitric oxide donating derivatives of evodiamine.

The first series of nitric oxide donating derivatives of evodiamine were designed and prepared. NO releasing ability of all target derivatives was evaluated in BGC-823, Bel-7402 and L-02 cells. The cytotoxicity was evaluated against three human tumor cell lines (Bel-7402, A549 and BGC-823) and normal human liver cells L-02. The nitrate derivatives 11a and 11b only exhibited moderate activity and furoxan-based derivatives 13a-c, 14a and 14b showed promising activity. 13c showed good cytotoxic selectivity between tumor and normal liver cells and was further investigated for its apoptotic properties on human hepatocarcinoma Bel-7402 cells. The molecular mode of action revealed that 13c caused cell-cycle arrest at S phase and induced apoptosis in Bel-7402 cells through mitochondria-related caspase-dependent pathways.

Terpenoids from the Marine-Derived Fungus Aspergillus fumigatus YK-7.

Two new ß-bergamotane sesquiterpenoids, E-ß-trans-5,8,11-trihydroxybergamot-9-ene (1) and ß-trans-2ß,5,15-trihydroxybergamot-10-ene (2), were isolated from the marine-derived fungus Aspergillus fumigatus YK-7, along with three known terpenoids 3-5. Their structures were determined by spectroscopic methods (1D and 2D NMR, HR-ESI-MS). Antiproliferative effects on human leukemic monocyte lymphoma U937 and human prostate cancer PC-3 cell lines were measured in vitro. Compound 4 exhibited potent activity against the U937 cell line with an IC50 value of 4.2 µM.

Caryophyllene sesquiterpenes from the marine-derived fungus Ascotricha sp. ZJ-M-5 by the one strain-many compounds strategy.

The marine-derived fungus Ascotricha sp. ZJ-M-5, which can produce cyclonerodiol analogues, a 3,4-seco lanostane triterpenoid, and diketopiperazines in an eutrophic medium, was subjected to a one strain-many compounds (OSMAC) analysis. It was found to produce three new caryophyllene derivatives (1-3) and the known 1,3,6-trihydroxy-8-methylxanthone (4) in an oligotrophic medium, Czapek Dox broth with or without Mg(2+). (+)-6-O-Demethylpestalotiopsin A (1) and (+)-6-O-demethylpestalotiopsin C (2), which have a five-membered hemiacetal structural moiety, showed growth inhibitory effects against HL-60 and K562 leukemia cell lines with the lowest GI50 value of 6.9 ± 0.4 µM. It can be concluded that modification of the culture media is still effective in the discovery of novel bioactive fungal secondary metabolites.

Anti-inflammatory diterpenoids from the roots of Euphorbia ebracteolata.

Thirteen diterpenoids (1-13), including two new norditerpene lactones (1-2) and eight new rosane diterpenoids (3-10), were isolated from the roots of Euphorbia ebracteolata. The structures were determined by 1D and 2D NMR, HRESIMS, and electronic circular dichroism (ECD). The ECD-based empirical rule for α,ß-unsaturated-γ-lactones was applied to determine the absolute configurations of 1 and 2. Compounds 7, 10, and 13 exhibited significant inhibition of nitric oxide production in RAW 264.7 lipopolysaccharide-induced macrophages, with IC50 values of 2.44, 2.76, and 1.02 µM, respectively.

Antimicrobial constituents from the flowers of Trollius chinensis.

A new 1-aryl-isochroman, trolliusol A (1), was isolated from the flowers of Trollius chinensis, along with seven known phenolic compounds in an antimicrobial activity-directed phytochemical investigation. The structures of these compounds were elucidated by spectroscopic methods, and their inhibitory activities against one fungus and four bacterial strains were measured.

A new steroid with long cross-conjugation structure from the marine-derived fungus Aspergillus aculeatus.

A new steroid with a long cross-conjugation structure, 15a-hydroxy-(22E, 24R)-ergosta-3, 5, 8 (14), 22-tetraen-7-one (1), was isolated from the marine-derived fungus Aspergillus aculeatus. Its structure was established by the extensive spectroscopic analyses, and its cytotoxicities against P388, HL-60, and PC-3 cell lines were measured in vitro.

Antiproliferative polycyclic polyprenylated acylphloroglucinols from Garcinia paucinervis.

Bioassay-guided isolation of the stems of Garcinia paucinervis led to one new adamantane-type polycyclic polyprenylated acylphloroglucinols (PPAPs), (-)-garpauvinin A (1), and four known analogues (2-5). The structure and absolute configuration of 1 was established via spectroscopic techniques and ECD method. All the isolates displayed moderate antiproliferative activity against HL-60, PC-3 and Caco-2 human cancer cell lines with IC50 values ranging from 0.81 to 19.92 µM, and exhibited low toxicity on WPMY-1 normal human cells, showing selectivity between normal and malignant prostate cells. The biosynthetic pathways of the isolated PPAPs were proposed.