Drimane Sesquiterpenoids from the Aspergillus oryzae QXPC‐4

Three new drimane sesquiterpenoids, astellolides C–E ( 1 – 3 , resp.), four new drimane sesquiterpenoid p‐hydroxybenzoates, astellolides F–I ( 4 – 7 , resp.), together with two known compounds astellolides A and B ( 8 and 9 , resp.), have been isolated from the liquid culture of Aspergillus oryzae (strain No. QXPC‐4). Their structures were established by comprehensive analysis of spectroscopic data. The relative and absolute configurations were determined on the basis of NOESY and CD data, together with single‐crystal X‐ray diffraction analyses of compounds 1 – 3 . The metabolites were evaluated for their cytotoxic activities, however, no compounds showed a significant cytotoxicity against the tested cell lines at a concentration of 20 μM .     

New Labdane Diterpenes and Their Glycoside Derivatives from the Roots of Isodon adenantha

Two new labdane‐type diterpenes (adenanthic acids A and B; 1 and 2 , resp.) and three new labdane diterpene glycosides (adenanthosides A–C; 3 – 5 , resp.) were isolated from the roots of Isodon adenantha, together with 23 known constituents including seven diterpenoids ( 6 – 12 ), eight triterpenoids ( 13 – 20 ), one lignan glycoside ( 21 ), six steroids ( 22 – 27 ), and one ceramide ( 28 ). Their structures were elucidated by spectroscopic methods including extensive 2D‐NMR techniques. Cytotoxicity and antibacterial activities of the samples were measured by the MTT method and the filter paper disc agar diffusion method. But none of them showed significant activities.     

Three New Isomeric Indole Alkaloids from Nauclea officinalis

Three new isomeric monoterpene indole alkaloids, naucleofficines I–III ( 1 – 3 , resp.) were isolated from the stems (with bark) of Nauclea officinalis. Their structures were elucidated on the basis of spectroscopic methods and single‐crystal diffraction analyses. The cytotoxic activities of 1 – 3 against human colon cancer, human gastric cancer, and human hepatoma cells were also investigated.     

Novel Zierane‐ and Guaiane‐Type Sesquiterpenes from the Root of Melicope denhamii

Two novel zierane‐type sesquiterpenes, named melicodenones A and B ( 1 and 2 , resp.), and three new guaiane‐type sesquiterpenes, named melicodenones C–E ( 3 – 5 ), were isolated from the root of Melicope denhamii (Seem. ) T. G. Hartley together with zierone ( 6 ). Their structures were established by extensive NMR‐spectroscopic analyses. Compounds 1 – 6 were tested for cytotoxicity using human colon cancer DLD‐1 cells, and melicodenone A ( 1 ) was found to exhibit moderate activity.     

Pierisformotoxins A – D,Polyesterified Grayanane Diterpenoids from Pieris formosa and Their cAMP‐Decreasing Activities

Four highly acylated diterpenoids, designated as pierisformotoxins A–D ( 1 – 4 , resp.), along with 26 known compounds, were isolated from the flowers of Pieris formosa. Among them, pierisformotoxins A and B ( 1 and 2 , resp.) were new highly acylated grayanane diterpenoids, of which the five‐membered ring A has undergone an oxidative cleavage between C(3) and C(4), followed by lactonization, to give rise to a five‐membered lactone ring between C(3) and C(5), differing from the previously reported grayanane diterpenoids with a 5/7/6/5 ring system. Results of the cAMP‐regulation‐activity assay showed that pierisformotoxin C ( 3 ) at 10 μM (inhibitory ratio (IR): 10.1%) or 2 μM (9.8%), and pierisformotoxin B ( 2 ) at 50 μM (13.9%) significantly decreased the cAMP level in N1E‐115 neuroblastoma cells (p<0.05).     

Cytotoxic Tetraprenylated Alkaloids from the South China Sea Gorgonian Euplexaura robusta

Nine achiral tetraprenylated alkaloids, including three new compounds, named malonganenones I–K ( 1 – 3 , resp.), together with six known analogs, 4 – 9 , were isolated from the gorgonian Euplexaura robusta collected from Weizhou Island of Guangxi Province, China. The structures of compounds 1 – 3 were elucidated by extensive spectral analyses, especially of their 1D‐ and 2D‐NMR data. Compounds 1, 4, 6 , and 7 showed moderate cytotoxicities against K562 and HeLa tumor cell lines with IC₅₀ values ranging from 0.35 to 10.82 μM . Compound 6 also showed moderate inhibitory activity against c‐Met kinase at a concentration of 10 μM .     

Crassocolides G–M,Cembranoids from the Formosan Soft Coral Sarcophyton crassocaule

Seven new polyoxygenated cembranoids possessing an α‐methylene‐γ‐lactone group, crassocolides G–M ( 1 – 7 , resp.), have been isolated from the AcOEt extract of the Formosan soft coral Sarcophyton crassocaule. The structures of compounds 1 – 7 were established by detailed spectroscopic analyses, including 2D‐NMR spectroscopy (¹H,¹H‐COSY, HMQC, HMBC, and NOESY), while the absolute configuration of 1 was determined using a modified reaction of Mosher's method. The cytotoxicity of compounds 1 – 7 against a limited panel of cancer cell lines was also determined.     

Identification and Antifeedant Activities of Limonoids from Azadirachta indica

Four new limonoids, azadiraindins A–D ( 1 – 4 , resp.), together with seven known analogs, were isolated from the MeOH extract of Azadirachta indica. The structures of 1 – 4 were elucidated by NMR and MS spectroscopic analyses, and the relative configuration of 1 was determined by single‐crystal X‐ray crystallography. The compounds isolated in comparatively large amount were evaluated for their antifeedant activities against Plutella xylostella; the antifeedant rate of 10 was 90.6% and the corrected mortality of 8 was 79.2%.     

Four New Flavonoids with α‐Glucosidase Inhibitory Activities from Morus alba var. tatarica

Four new flavonoids, mortatarins A–D ( 1 – 4 , resp.), along with eight known flavonoids ( 5 – 12 ) were isolated from the root bark of Morus alba var. tatarica. Their structures were established on the basis of spectroscopic data analysis, and the absolute configuration of 4 was determined by analysis of its CD spectrum. All isolates were tested for inhibitory activities against α‐glucosidase. Compounds 4, 7 , and 8 exhibited a significant degree of inhibition with IC₅₀ values of 5.0±0.3, 7.5±0.5, and 5.9±0.2 μM , respectively.     

Inhibitory Effects of Maleimide Derivatives from the Mycelia of the Fungus Antrodia cinnamomea BCRC 36799 on Nitric Oxide Production in Lipopolysaccharide (LPS)‐Activated RAW264.7 Macrophages

Four new maleimide derivatives, antrocinnamomins E–H ( 1 – 4 , resp.), together with (3S,4R)‐1‐hydroxy‐3‐(4‐hydroxyphenyl)‐4‐(2‐methylpropyl)pyrrolidine‐2,5‐dione ( 5 ) and ergosterol were isolated from the mycelia of Antrodia cinnamomea BCRC 36799. The structures were elucidated by 1D‐ and 2D‐NMR spectroscopy, and mass spectrometry. Compounds 1 – 5 were evaluated for their inhibitory effects on nitric oxide (NO) production by macrophages. Compounds 2 and 4 showed stronger inhibition of NO production than the positive control quercetin.     

Triterpenoids from the Stem Bark of Melia toosendan and Determination of Their Absolute Configurations at C(24)

Six new triterpenoids, meliasenins S–X ( 1 – 6 , resp.), were isolated from the stem bark of Melia toosendan. Their structures were elucidated by mass spectrometry, NMR experiments, and comparison with the known compounds. Particularly, the absolute configuration at C(24) in new compounds was determined through their CD spectra of the [Pr(FOD)₃] complex (fod=1,1,1,2,2,3,3,7,7,7‐decafluoroheptane‐4,6‐dione) in CCl₄, as well as by using Mosher's method.     

Antituberculosis Agents and an Inhibitor of the para‐Aminobenzoic Acid Biosynthetic Pathway from Hydnocarpus anthelminthica Seeds

Investigation on the extracts of Hydnocarpus anthelminthica seeds led to the isolation of three new compounds, anthelminthicins A–C ( 1 – 3 , resp.), and two known ones, namely chaulmoogric acid ( 4 ) and ethyl chaulmoograte ( 5 ). Their structures were determined mainly by using spectroscopic techniques. The absolute configuration at the cyclopentenyl moiety of compound 2 was rationalized by quantum calculations. Base hydrolysis, followed by optical‐rotation comparison, allowed assignment of the configuration of chaulmoogric‐acid moiety of compounds 3 and 5 . Biological assays revealed that compounds 1 – 5 significantly inhibit Mycobacterium tuberculosis (MTB) growth with MIC values of 5.54, 16.70, 4.38, 9.82, and 16.80 μM , respectively. Compound 3 was found to inhibit the pathway between chorismate and para‐aminobenzoic acid (pAba) with a MIC value of 11.3 μM , representing a new example of pAba inhibitor isolated from a natural source. All compounds were not toxic to Candida albicans SC5314 at a concentration up to 100 μM .     

Cytotoxic ent‐Kaurane Diterpenoids from Isodon nervosus

Four new ent‐kaurane diterpenoids, rabdonervosins G–J ( 1 – 4 , resp.), were isolated from the leaves and stems of Isodon nervosus. Their structures were elucidated by extensive spectroscopic analyses, including 1D‐, 2D‐NMR and HR mass spectra. Compound 2 showed potent cytotoxicity against the HepG2 and PC‐9/ZD cell lines with IC₅₀ values of 2.36 and 6.07 μM , respectively, and compound 3 exhibited cytotoxicity against the HepG2 and CNE2 cell lines with IC₅₀ values of 8.64 and 9.77 μM , respectively.     

Immunosuppressive Withanolides from Withania coagulans

Six new withanolides, withacoagulins A–F ( 1 – 6 , resp.), together with ten known withanolides, 7 – 16 , were isolated from the aerial parts of Withania coagulans. Their structures were determined by spectroscopic techniques including 1D‐ and 2D‐NMR (¹H, ¹³C, HMQC, and HMBC) and MS experiments. These compounds, including the crude extracts of this herb, exhibited strong inhibitory activities on the T‐ and B‐cell proliferation.     

New 3,4‐Secocycloartane and 3,4‐Secodammarane Triterpenes from the Ecuadorian Plant Coussarea macrophylla

Coussarea macrophylla (Mart .) Müll.Arg . (Rubiaceae) was collected in Ecuador, and the bark was extracted with AcOEt. Chromatographic separation afforded six novel 3,4‐secocycloartane and 3,4‐secodammarane triterpenes, named macrocoussaric acids A–F, together with the known metabolites secaubryenol and 3,4‐secodammara‐4(28),20,24‐triene‐3,26‐dioic acid. The structures of the new compounds were determined on the basis of their spectroscopic data. This is the first report of 3,4‐secocycloartane and 3,4‐secodammarane triterpenes occurring in a Coussarea species. Macrocoussaric acids A and B ( 2 and 3 , resp.) were found to be moderately cytotoxic against five different tumor cell lines.     

Bioactive Diphenyl Ether Derivatives from a Gorgonian‐Derived Fungus Talaromyces sp.

Three new diphenyl ether derivatives, talaromycins A–C ( 1 – 3 , resp.), together with six known analogs, 4 – 9 , were isolated from a gorgonian‐derived fungus, Talaromyces sp. The structures of the new compounds were determined by analysis of extensive NMR spectroscopic data. All of the isolated metabolites, 1 – 9 , were evaluated for their cytotoxic and antifouling activities. Compound 4 exhibited pronounced cytotoxicity against the tested human cell lines with the IC₅₀ values ranging from 4.3 to 9.8 μM . Compounds 3, 5, 8 , and 9 showed potent antifouling activities against the larval settlement of the barnacle Balanus amphitrite with the EC₅₀ values ranging from 2.2 to 4.8 μg/ml.     

Tirucallane Triterpenoids from the Stems of Brucea mollis

Three new tirucallane triterpenoids, brumollisols A–C ( 1 – 3 , resp.), together with five known analogues, (23R,24S)‐23,24,25‐trihydroxytirucall‐7‐ene‐3,6‐dione ( 4 ), piscidinol A ( 5 ), 24‐epipiscidinol A ( 6 ), 21α‐methylmelianodiol ( 7 ), and 21β‐methylmelianodiol ( 8 ), were isolated from an EtOH extract of the stems of Brucea mollis. Their structures were elucidated by means of spectroscopic methods including 1D‐ and 2D‐NMR techniques and mass spectrometry. In the in vitro assays, compound 6 exhibited significant cytotoxic activity against A549 and BGC‐823 cancer cells with IC₅₀ values of 1.16 and 3.01 μM , respectively. At a concentration of 10 μM , compounds 1 – 5, 7 , and 8 were found to inhibit NO production in mouse peritoneal macrophages with inhibitory ratios ranging from 39.8±7.7 to 68.2±4.5%.     

Netamines O–S,Five New Tricyclic Guanidine Alkaloids from the Madagascar Sponge Biemna laboutei,and Their Antimalarial Activities

In our continuing program to isolate new compounds from the Madagascar sponge Biemna laboutei, five new tricyclic guanidine alkaloids, netamines O – S ( 1 – 5 , resp.), have been identified together with the known compounds netamine E ( 6 ) and mirabilin J ( 7 ). The structures of all new netamines were assigned on the basis of spectroscopic analyses. Their relative configurations were established by analysis of ROESY data and comparison with literature data. Netamines O, P, and Q, which were isolated in sufficient quantities, were tested for their cytotoxic activities against KB cells and their activities against the malaria parasite Plasmodium falciparum. Netamines O and Q were found to be moderately cytotoxic. Netamines O, P, and Q exhibited antiplasmodial activities with IC₅₀ values of 16.99±4.12, 32.62±3.44, and 8.37±1.35 μM , respectively.     

Sinuladiterpenes A–F,New Cembrane Diterpenes from Sinularia flexibilis

Chromatographic investigation of the octocoral Sinularia flexibilis afforded six new cembrane diterpenes, sinuladiterpenes A–F ( 1 – 6 , resp.), in addition to four known cembranolides, 11‐episinulariolide acetate, 11 ‐ dehydrosinulariolide, 11‐episinulariolide, and sinulariolide. Their structures were elucidated by spectroscopic analysis, especially 2D‐NMR and HR‐ESI‐MS. Compound 2 exhibited significant in vitro cytotoxic activity against human colon adenocarcinoma (WiDr) cell line.     

Bioactive Xenicane Diterpenoids from the Taiwanese Soft Coral Asterospicularia laurae

Chemical investigation of the Taiwanese soft coral Asterospicularia laurae has led to the isolation of three new xenicane diterpenoids, named asterolaurins K–M ( 1 – 3 , resp.). Their chemical structures were determined through extensive spectroscopic analyses (¹H‐ and ¹³C‐NMR, ¹H,¹H‐COSY, HMBC, and NOESY). Compound 2 exhibited cytotoxic activity against HEp‐2, Daoy, MCF‐7, and WiDr tumor cells.