Secondary metabolites of the lichen-associated fungus Apiospora montagnei

The endolichenic fungus Apiospora montagnei isolated from the lichen Cladonia sp. was cultured on solid rice medium, yielding the new diterpenoid libertellenone L (1), the new pyridine alkaloid, 23-O-acetyl-N-hydroxyapiosporamide (2) and the new xanthone derivative 8-hydroxy-3-hydroxymethyl-9-oxo-9H-xanthene-1-carboxylic acid methyl ether (3) together with 19 known compounds (4–22). The structures of the new compounds were elucidated by 1D and 2D NMR spectra as well as by HRESIMS data. The absolute configuration of the new 6,7-seco-libertellenone derivative 1 was determined by single-crystal X-ray diffraction. Four additional known compounds 23–26 were isolated when NaCl or NH₄Cl were added to solid rice medium. Compounds 7–9, 18 and 26 exhibited significant cytotoxicity against the L5178 murine lymphoma cell line with IC₅₀ values of 2.6, 0.2, 2.1, 2.7 and 1.7 μM, respectively.     

Complanadine B, obscurumines A and B, new alkaloids from two species of Lycopodium

A new dimer of C₁₆N₂ type alkaloid, complanadine B (1), and two new C₁₆N type alkaloids, obscurumines A (2) and B (3), have been isolated from the club moss Lycopodium complanatum and L. obscurum, respectively. The structures and stereochemistry of 1-3 were elucidated by combination of 2D NMR spectra and chemical transformation. Complanadine A (4) isolated together with 1 induced secretion of neurotrophic factors from human astrocytoma cells.     

A new steroid with unique rearranged seven-membered B ring isolated from roots of Asparagus filicinus

A novel skeleton steroid aspafilisine (1), which has a unique rearranged seven-membered B ring formed by the C₍₇₎–C₍₁₄₎ linkage were isolated from the roots of Asparagus filicinus. A novel hemiketal derivative (1a) was synthesized to identify the structure of 1. The structures of 1 and 1a were elucidated by 1D and 2D NMR spectra as well as by HRESIMS data. The absolute configuration of 1 was assigned on the basis of ROESY spectrum, comparison with literature and computational methods. A plausible biosynthetic pathway of 1 was also proposed.     

Additional cytotoxic substances isolated from the sponge-derived Gymnascella dankaliensis

A continuous investigation of secondary metabolites produced by the sponge-derived fungus, Gymnascella dankaliensis, has yielded a new polyketide tyrosine derivative, dankastatin C (3) and the known steroid, demethylincisterol A₃ (4), which was originally found from a Homaxinella marine sponge. The stereostructure of the new compound has been determined based on the analysis of 1D and 2D NMR data. Dankastatin C (3) showed potent cell growth inhibitory activity against the murine P388 cell line.     

Characterization and cytotoxicity of ellagitannins from Stachyurus praecox fruit

This study aimed to characterize and evaluate the cytotoxicities of ellagitannins from S. praecox fruit. Fractionation of an acetone extract of the fruit led to isolation of five new ellagitannins—stachyuranin D (15), stachyuranin E (16), stachyuranin F (17), stachyugluconin (18), and stachyuglyconin (19)—along with seven ellagitannins previously isolated from S. praecox leaves and seven known ellagitannins isolated from Stachyuraceae for the first time. Two-dimensional NMR and other spectroscopic methods enabled complete elucidation of the structures of the new compounds. Structure of flavanoellagitannin (16) was confirmed by ¹H NMR comparison with synthetic analogs. The configuration of stachyuglyconin (19) with a C₈-aldonic acid core was established with the aid of density functional theory calculations. A MTT assay revealed 5-desgalloylpterocarinin A (11) and hippophaenin B (9) had the highest cytotoxicities among the compounds against HeLa (IC₅₀ = 35.35 μM) and HepG2 (IC₅₀ = 60.00 μM) cells, respectively.     

Kingamide A, a new indole alkaloid from the ascidian Leptoclinides kingi

Chemical investigation of the CH₂Cl₂/MeOH extract from the Australian ascidian Leptoclinideskingi led to the isolation of a new brominated indole alkaloid, kingamide A (1). The planar structure of kingamide A was elucidated following the interpretation of 1D/2D NMR and MS data, and the absolute configuration was determined using Marfey’s method. This is the first report of a natural product from L. kingi.     

Amphimedonoic acid and psammaplysene E,novel brominated alkaloids from Amphimedon sp.

Examination of the CH₂Cl₂-MeOH (1:1) extract from the Madagascan sponge Amphimedon sp. highlighted two new brominated alkaloids, amphimedonoic acid (1) and psammaplysene E (2), along with the known 3,5-dibromo-4-methoxybenzoic acid (3). Their structures were elucidated by 1D and 2D NMR spectroscopy and HRESIMS data.     

New biphenantherene and nervogenic acid derivatives from Liparis regnieri Finet and their inhibitory activities against NF-κB activation

A phytochemical investigation of the whole plant of Liparis regnieri Finet led to the isolation of one new biphenantherene (1) and ten new nervogenic acid derivatives (2–11), together with nine known compounds. Their structures were elucidated mainly by extensive analyses of 1D and 2D NMR spectroscopic data and chemical reactions. Additionally, for the first time a previously unreported biphenantherene was discovered to effectively suppress TNF-α induced expression of NF-κB-Luc in Hela cells with the IC₅₀ value of 1.80 μM and the structure-activity relationshipwas also discussed.     

Pellynols M−O,cytotoxic polyacetylenic alcohols from a Niphates sp. marine sponge

Three new polyacetylenic alcohols, pellynols M?O (1–3), along with two known ones, melyne A (4) and melyne B (5), were isolated from a Niphates sp. marine sponge collected off the South China Sea. The structures of new compounds were determined based on a combination of 1D and 2D NMR analysis, ESI-MSⁿ fragmentation, and chemical (ozonolysis) method. Their absolute configurations were assigned by modified Mosher's method. All the isolates showed potent cytotoxic activity against PC9 and HepG2 human cancer cell lines with IC₅₀ values of 2.9–7.6?μM.     

Vincamajorines A and B,monoterpenoid indole alkaloids with new carbon skeletons from Vinca major

Two new monoterpenoid indole alkaloids, vincamajorines A (1) and B (2), were isolated from Vinca major. Their structures were elucidated by means of 1D and 2D NMR, and HREIMS spectroscopic data. The relative and absolute configurations were deduced by comparing the experimental ¹³C NMR, ECD spectra, and OR data with those theoretically calculated. Vincamajorine A (1) represents a new C₂₀ carbon skeleton arranged compactly in seven rings, and vincamajorine B (2) is an alkaloid with an unprecedented 6/5/7/5/6 pentacyclic ring system. A possible biosynthetic pathway was also proposed for the formation of 1 and 2.     

Anti-inflammatory polyketides from the mangrove-derived fungus Ascomycota sp. SK2YWS-L

A pair of novel 2,3-diaryl indone derivatives (+)- and (?)-ascomindone D [(+)-1 and (?)-1, respectively], as well as two new prenylated polyketides ascomfurans C (2) and ascomarugosin A (3) were obtained from the culture of a mangrove endophytic fungus Ascomycota sp. SK2YWS-L together with three known compounds (4–6). The enantiomers (+)-1 and (?)-1 were purified through chiral HPLC separation, which represented the first example of resolving 2,3-diaryl indone atropisomers in natural products. The structures of the new compounds were determined on the basis of interpretation of spectroscopic data including X-ray diffractions and the absolute configurations of (+)-1 and (?)-1 were elucidated by ECD calculations. The biosynthesis pathway was proposed. In the anti-inflammatory assay, (+)-1 and (?)-1 exhibited potential anti-inflammatory effects by inhibiting against the production of nitric oxide (NO) in lipopolysaccharide (LPS)-induced RAW 246.7 mouse macrophages with the IC₅₀ values of 17.0 and 17.1 μM, respectively.     

Antitrypanosomal pyridoacridine alkaloids from the Australian ascidian Polysyncraton echinatum

Bioassay-guided fractionation of the crude CH₂Cl₂/MeOH extract from the Australian ascidian Polysyncraton echinatum led to the isolation of a new pyridoacridine alkaloid, 12-deoxyascididemin (1), along with two known analogues, ascididemin (2) and eilatin (3). The structure of 1 was determined following extensive analysis of 1D/2D NMR and MS data. Biological evaluation showed that compounds 1-3 are potent antitrypanosomal agents with IC₅₀ values of 0.077, 0.032, and 1.33 μM against Trypanosoma brucei brucei, respectively.     

Physalinol A,a 1,10-seco-physalin with an epidioxy from Physalis alkekengi L. var. franchetii (Mast.) Makino

Physalinol A (1), a novel 1, 10-seco-physalin with a peroxy bridge, was isolated from the organic extracts of Physalis alkekengi L. var. franchetii (Mast.) Makino. The structure was determined on the basis of 1D and 2D NMR spectra and HR-ESI-MS data. The absolute configuration of 1 was evidenced by X-ray diffraction data and further confirmed by ECD calculations. The isolated compound 1 has no cytotoxicity against HCT-116 and PC-3 cancer cell lines and a weak antimicrobial activity against Escherichia coil. In addition, compound 1 also exhibited a weak anti-inflammatory action in lipopolysacaride (LPS)-induced RAW 264.7 macrophages with an IC₅₀ value of 57.3?±?1.03?μM.     

Meroterpenoids with diverse ring systems and dioxolanone-type secondary metabolites from Phyllosticta capitalensis and their phytotoxic activity

Twenty meroterpenoids with diverse ring systems including five new ones (1, 2, 5, 6, and 15), together with two new (23 and 24) and two known dioxolanone-type secondary metabolites were isolated from Phyllosticta capitalensis, an endophytic fungus from Cephalotaxus fortunei Hook. Compound 1 was the first example with a 9,14-seco ring A and a five-membered ring B in guignardone derivatives. Compound 2 represented a novel guignardone derivative possessing a 5/7/6/5 ring system with CH₂-7 attached to C-4 rather than C-6 in ring D. The structures of all new compounds were elucidated using spectroscopic data analyses and electronic circular dichroism comparison. The phytotoxic effects of compounds 1–24 on Lactuca sativa and Lolium perenne were evaluated. Compound 22 showed inhibition activity on the shoots growth of L. sativa and L. perenne, as well as the roots growth of L. perenne.     

A new rearranged and a new seco-ent-kaurane diterpenoids from Isodon parvifolius

Parvifoline X (1), a new rearranged ent-kaurane diterpenoid, and parvifoline Y (2), a new 8,15-seco-ent-kaurane diterpenoid, were isolated from the leaves of Isodon parvifolius. Their structures were elucidated by spectroscopic methods including 2D NMR analysis, and supported by a biogenetic pathway. Parvifoline X (1), possessing a new 15(8→11)-abeo-7α,20-epoxy-ent-kaurane skeleton, was found from the genus Isodon for the first time. Compounds 1 and 2 were evaluated for their inhibitory activity against A549, HT-29, and K562 cell lines. Parvifoline Y (2) was the most cytotoxic against A549 cells with an IC₅₀ value of 4.97 μM.     

Acylphloroglucinol derivatives from the twigs and leaves of Callistemon salignus

Three new acylphloroglucinol derivatives, callisalignones A–C (1–3), six new meroterpenoids, callisalignenes A–F (4–9), along with 18 known analogues (10–27) were isolated from the twigs and leaves of Callistemon salignus. Their structures and absolute configurations were established by comprehensive spectroscopic evidences (NMR, MS, amd electronic circular dichroism calculations). The absolute configurations of callistenones B (13) and H (14) were determined by comparison of their ECD spectra with that of callisalignone B (2). Callisalignones B and C are new adducts of β-triketone and acylphloroglucinol, whereas callisalignenes A–D are new meroterpenoids of acylphloroglucinol and α-phellandrene with different coupling models via hetero-Diels-Alder reaction, respectively. Myrtucommulone D (15) showed significant antibacterial activity against Staphylococcus aureus and three drug resistant S. aureus strains with MIC values of 1.953 and 0.975 μg/mL, respectively. Isomyrtucommulone B (17) displayed remarkable antibacterial activity against Escherichia coli with an MIC value of 0.122 μg/mL. Cytotoxic assay revealed that isomyrtucommulone B (17) was the most active against HCT116 with an IC₅₀ value of 2.09 ± 0.10 μM.     

Cytosporins F–K,new epoxyquinols from the endophytic fungus Pestalotiopsis theae

Chemical investigation of an endophytic fungus, Pestalotiopsis theae, isolated from the leaves of Turraeanthus longipes (Meliaceae) collected in Cameroon, resulted in the isolation of six new epoxyquinols, cytosporins F–K (2–7), together with the known cytosporin D (1). The structures of the new compounds were unambiguously determined by analysis of the 1D, 2D NMR, and HRMS spectra. Cytosporins G–K (3–7) are the first cytosporins with a hydroxyl substituted C₇ side chain, while cytosporins F–I (2–5) contain a 13-acetoxyl group that was not reported previously. A plausible biosynthetic pathway for the cytosporin derivatives is proposed.     

Antiviral peptides from marine gorgonian-derived fungus Aspergillus sp. SCSIO 41501

A new cyclic pentapeptide and three new linear peptides, namely, aspergillipeptides D–G (1–4), were isolated from a culture broth of marine gorgonian-derived fungus Aspergillus sp. SCSIO 41501. Their structures were elucidated by spectroscopic analysis, and their absolute configurations were confirmed by Marfey’s method. Compounds 1 and 2 showed evident antiviral activity against herpes simplex virus type 1 (HSV-1) with IC₅₀ values of 9.5 and 19.8 µM under their non-cytotoxic concentrations against a Vero cell line, respectively, and 1 also had antiviral activity against acyclovir-resistant clinical isolates of HSV-1.     

Cytotoxic labdane diterpenes and bisflavonoid atropisomers from leaves of Araucaria bidwillii

Chemical investigation of a methanolic extract of leaves from Araucaria bidwillii (Araucariaceae) from Egypt afforded four new labdane diterpenoidal metabolites (1–4) together with one known diterpene, 7-oxocallitrisic acid (5), two triterpenoidal metabolites, 2-O-acetyl-11-keto-boswellic acid (6) and β-sitosterol-3-O-glucopyranoside (7), phloretic acid (8), and two methylated bisflavonoids, agathisflavone-4′,7,7″-trimethyl ether (9) and cupressuflavone-4′,7,7″-trimethyl ether (10). The new metabolites 1–4 were unambiguously identified by applying extensive 1D and 2D NMR spectroscopic studies as well as HRESIMS. The relative and absolute configurations of 1–4 were determined using ROESY and the modified Mosher's method, respectively. All isolated compounds were assessed for their antimicrobial, antitubercular and cytotoxic activities. Among the tested compounds, the new labdane diterpenes 1–4 revealed significant cytotoxic activity against mouse lymphoma L5178Y cell line with IC₅₀ values ranging from 1.4 to 12.9 μM, respectively.     

Neomerane-type sesquiterpenoids from Valeriana officinalis var. latifolia

Valeneomerins A–D, two new neomerane-type sesquiterpenoids and two new nor-sesquiterpenoids, were isolated from the roots of Valeriana officinalis var. latifolia. Among them, valeneomerin A (1) was identified as a sesquiterpenoid with an unprecedented 15,3-lactone loop while valeneomerin C (3) and valeneomerin D (4) were determined to be nor-sesquiterpenoids with a new 15-reductive neomerane-type carbon skeleton. Their structures were elucidated by detailed spectroscopic analysis and Cu Kα X-ray crystallography. Compounds 1, 2, and 4 exhibited significant neuroprotective effects against H₂O₂ induced oxidative stress in SH-SY5Y cells with viability of 49.8, 40.9, and 44.6% each at 50 μM, respectively, in contrast to positive control (catechin, 50 μM) with viability of 32.6%.