Longipedlactones A-I, nine novel triterpene dilactones possessing a unique skeleton from Kadsura longipedunculata

Nine novel triterpene dilactones with an unprecedented rearranged pentacyclic skeleton, longipedlactones A-I (1-9), have been isolated from the leaves and stems of Kadsura longipedunculata Finet et Gagnep (Schisandraceae). Their structures were determined on the basis of comprehensive spectroscopic analysis and single-crystal X-ray structure determination. A biogenetic pathway for longipedlactone A (1) was also proposed. Compounds 1-3, 6, and 8 showed significant cytotoxicity against A549, with HT-29 and K562 cell lines having IC₅₀ values of 0.84-11.38 μM in vitro.     

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.     

Takaneones A-C, prenylated butylphloroglucinol derivatives from Hypericum sikokumontanum

Three new prenylated butylphloroglucinol derivatives, takaneones A-C (1-3), were isolated from the MeOH extracts of the aerial parts of Hypericum sikokumontanum together with two new prenylated phloroglucinol derivatives, takaneols A and B (4 and 5). The structures of the isolated compounds were elucidated by exhaustive spectroscopic analysis. The cytotoxicities of the isolated compounds against human cancer cell lines were evaluated. Compounds 2-4 showed cytotoxicities against K562/Adr multi-drug resistant (MDR) cancer cells with IC₅₀ values ranging from 4.7 to 10.0 μg/mL, which were slightly more potent than doxorubicin. Their potency of cytotoxicities against MDR cancer cell lines (KB-C2 and K562/Adr) were similar to those against sensitive cell lines (KB and K562).     

Pre-schisanartanins C-D and propintrilactones A-B, two classes of new nortriterpenoids from Schisandra propinqua var. propinqua

Four new nortriterpenoids, pre-schisanartanins C and D (1-2) with pre-schisanartane backbone, and propintrilactones A and B (3-4) possessed wuweiziartane framework, were isolated from the acetone extract of the stems of Schisandra propinqua var. propinqua. Their structures were characterized by extensive spectroscopic analyses. Compounds 3 and 4 existed as a pair of slowly interconverting diastereomers at room temperature; their absolute configuration was established by CD methods. Compounds 1-4 showed no cytotoxicity against K562, A549, and HT-29 human cancer cells.     

Novel cytotoxic icetexane diterpenes from Premna latifolia Roxb

Chromatographic fractionation of a hexane extract from stem-bark of Premna latifolia yielded three new icetexane diterpenes (1-3). Their structures were elucidated on the basis of spectroscopic data, mainly NMR and MS, data. Compounds 1-3 were also evaluated for the cytotoxicity against the cancer cell lines (HT-29, A-431, MCF-7, Hep-G2, PC-3, A-549, B-16 F10 and ACHN). Compounds 1 and 2 displayed potent cytotoxic activity against HT-29 and Hep-G2 cell lines with IC₅₀ values of 0.04 and 0.18 μg/mL, respectively.     

3,4-seco-Diterpenoids from Trigonostemon flavidus

Phytochemical investigation on the stems of Trigonostemon flavidus resulted in the isolation of five new 3,4-seco-diterpenoids, trigoflavidones A-E (1-5), structurally related to the main co-occurring known 3,4-seco-sonderianic acid (6) and 3,4-seco-sonderianol (7). Compound 4 possesses new 3,4-seco rearranged ent-pimarane skeletal type, characteristic of a vinyl group at C-8, while 5 features a unique five-membered ring (C₁) fused with a cyclopropane ring (C₂). The structures of the new compounds were established by a combination of spectroscopic data and computational methods. Compounds 1-7 were tested for their cytotoxicities on HL-60, SMMC-7721, A-549, MCF-7, and SW480 human tumor cell lines.     

Aspergiolide A, a novel anthraquinone derivative with naphtho[1,2,3-de]chromene-2,7-dione skeleton isolated from a marine-derived fungus Aspergillus glaucus

Aspergiolide A (1), an anthraquinone derivative with naphtho[1,2,3-de]chromene-2,7-dione skeleton, has been isolated from cultures of a marine-derived fungus Aspergillus glaucus. The structure and stereochemistry of 1 was determined by NMR and X-ray diffraction analyses. Compound 1 showed selective cytotoxicities against A-549, HL-60, BEL-7402, and P388 cell lines.     

Eight new limonoids from Turraea pubescens

Eight new ring B-seco limonoids, turrapubesic acids A-C (1-3) and turrapubesins C-G (4-8), along with turraflorin E and isoazadironolide were isolated from the twigs and leaves of Turraea pubescens. Turrapubesic acids A-C (1-3) are a group of ring B-seco limonoid 17-carboxylic acids with a new C₂₃ skeleton, and turrapubesin C (4) incorporates an unprecedented 1,30-oxygen bridge. The structures including absolute stereochemistry of 1-8 were established on the basis of extensive NMR spectroscopic analysis and CD study. The cytotoxicity of the isolates against the P-388 and A-549 cells was evaluated.     

New alkaloids and diterpenes from a deep ocean sediment derived fungus Penicillium sp.

Four new alkaloids, including two new meleagrin analogs, meleagrins B (2) and C (3), and two new diketopiperazines, roquefortines F (5) and G (6), together with six new diterpenes, conidiogenones B-G (7-12), were isolated from a deep ocean sediment derived fungus Penicillium sp. The structures and stereochemistry of the new compounds were elucidated by spectroscopic methods. The cytotoxicity of the new compounds against the HL-60, A-549, BEL-7402, and MOLT-4 cell lines was evaluated.     

Cytotoxic ent-kauranoid derivatives from Isodon rubescens

An extensive study of the diterpenoids produced by the species of Isodon rubescens, has led to the isolation of 12 new ent-kaurane diterpenoids, hebeirubescensins A-L (1-12), and 19 known analogues. Their structures were determined on the basis of spectroscopic analysis. Selected compounds were assayed for their inhibitory ability against human A549, HT-29, and K562 cells. Among them, hebeirubescensins B and C exhibited significant cytotoxicity with IC₅₀ values of <2.0 μM. The structure-activity relationships were discussed.     

Chloctanspirones A and B, novel chlorinated polyketides with an unprecedented skeleton, from marine sediment derived fungus Penicillium terrestre

Two novel chlorinated sorbicillinoids named chloctanspirones A (1) and B (2), possessing an unprecedented bicyclo[2.2.2]octane-2-spiro cyclohexane skeleton, together with their quasi-precursors terrestrols K (3) and L (4), two additional new chlorinated compounds, were isolated from a marine sediment derived fungus Penicillium terrestre. Their structures including absolute stereochemistries were elucidated by analysis of NMR, MS data, and TDDFT CD calculations. The cytotoxic effects of 1-4 were preliminarily evaluated in HL-60 and A-549 cells. Compound 1 was active against both HL-60 and A-549 cells with IC₅₀s 9.2 and 39.7 μM, respectively, while 2 showed weaker activity only against HL-60 cells (IC₅₀ 37.8 μM).     

Novel carbon-bridged citrinin dimers from a volcano ash-derived fungus Penicillium citrinum and their cytotoxic and cell cycle arrest activities

Three novel carbon-bridged citrinin dimers, dicitrinones A-C (1-3), were isolated from a volcano ash-derived fungus Penicillium citrinum. Their structures were elucidated by spectroscopic methods. Dicitrinone A (1) and B (2) are two atropisomeric mixtures, which were verified by both NMR and quantum chemical calculations. Their cytotoxicity against four tumor cell lines (HL-60, MOLT-4, A-549, and BEL-7402) was evaluated by SRB and MTT methods. Dicitrinone B (2) arrested the HL-60 cell cycle at the G2/M phase, which was analyzed using flow cytometry.     

Three new sulfur-containing alkaloids, polycarpaurines A, B, and C, from an Indonesian ascidian Polycarpa aurata

Three new sulfur-containing alkaloids, polycarpaurines A (1), B (2), and C (3) were isolated from the tropical ascidian Polycarpa aurata collected in Indonesia, together with six known compounds (4-9). The structures of new compounds were assigned on the basis of their spectral data. Compounds 1, 3, 4, and 8 inhibited colony formation of Chinese hamster V79 cells with EC₅₀ values of 6.8, 8.6, 3.8, and 10 μM, respectively. Compounds 2 and 7 showed modest activity against V79 cells (EC₅₀>10 μM).     

Guignardins A–F,spirodioxynaphthalenes from the endophytic fungus Guignardia sp. KcF8 as a new class of PTP1B and SIRT1 inhibitors

Six new guignardins A–F (1–6) were isolated from the cultures of endophytic fungus Guignardia sp. KcF8 derived of a mangrove plant Kandelia candel, along with three known analogues, palmarumycins C₁ (7), BG1 (8), and JC1 (9). Compounds 2, 3, 7, and 8 showed antimicrobial activities. Compounds 5–7 exhibited significant cytotoxicities against 10 human tumor cell lines. Compound 3 also displayed significant inhibitory activity against human protein tyrosine phosphatase 1B and histone deacetylase silent information regulator T1enzymes, two key targets for the treatment of diabetes. This is the first report on the anti-PTP1B and anti-SIRT1 activities of spirodioxynaphthalenes.     

Withaphysanolide A, a novel C-27 norwithanolide skeleton, and other cytotoxic compounds from Physalis divericata

A novel C-27 norwithasteroid, withaphysanolide A (1) containing a pyran ring was isolated from the aerial parts of Physalis divericata. Four known withaphysalins (2-5) and five physalins (6-10) were also isolated. The structural assignment for 1 was done based on spectroscopic and single-crystal X-ray diffraction data. Logical biosynthetic pathways were postulated. Compounds 6, 7, and 10 displayed potent cytotoxic activity against HCT-116 and H460 human cancer cell lines, with IC₅₀ values less than 2.0 μM.     

3-Oxyanthranilic acid derivatives from Actinomadura sp. BCC27169

Eight new compounds including 9′-[2-amino-3-(4″-O-methyl-α-rhamnopyranosyloxy) phenyl]nonanoic acid (1), 9′-[2-amino-3-(4″-O-methyl-α-ribopyranosyloxy)phenyl] nonanoic acid (2), 11′-[2-amino-3-(4″-O-methyl-α-rhamnopyranosyloxy)phenyl]undecanoic acid (3), 11′-[2-amino-3-(4″-O-methyl-α-ribopyranosyloxy)phenyl]undecanoic acid (4), 8-(4′-O-methyl-α-rhamnopyranosyloxy)-3,4-dihydroquinolin-2(1H)-one (5), 8-(4′-O-methyl-α-ribopyranosyloxy)-3,4-dihydroquinolin-2(1H)-one (6), 8-(4′-O-methyl-α-rhamnopyranosyloxy)-2-methyquinoline (7), and 8-(4′-O-methyl-α-ribopyranosyloxy)-2-methylquinoline (8) were isolated from Actinomadura sp. BCC27169. The chemical structures of these compounds were determined based on NMR and high-resolution mass spectroscopy. The absolute configurations of these monosaccharides were revealed by the hydrolysis of compounds 7 and 8. Compounds 3 and 8 exhibited antitubercular activity at MIC 50 μg/mL. Only compound 3 showed cytotoxicity against KB cell at IC₅₀ 18.63 μg/mL, while other isolated compounds were inactive at tested maximum concentration (50 μg/mL).     

Antileukemic α-pyrone derivatives from the endophytic fungus Alternaria phragmospora

Four new (1–4) and two known (5 and 6) α-pyrone derivatives have been isolated from Alternaria phragmospora, an endophytic fungus from Vinca rosea, leaves. The isolated compounds were chemically identified to be 5-butyl-4-methoxy-6-methyl-2H-pyran-2-one (1), 5-butyl-6-(hydroxymethyl)-4-methoxy-2H-pyran-2-one (2), 5-(1-hydroxybutyl)-4-methoxy-6-methyl-2H-pyran-2-one (3), 4-methoxy-6-methyl-5-(3-oxobutyl)-2H-pyran-2-one (4), 5-(2-hydroxyethyl)-4-methoxy-6-methyl-2H-pyran-2-one (5), and 5-[(2E)-but-2-en-1-yl]-4-methoxy-6-methyl-2H-pyran-2-one (6). Compounds 2 and 4 showed moderate antileukemic activities against HL60 cells with IC₅₀ values of 2.2 and 0.9 μM and against K562 cells with IC₅₀ values of 4.5 and 1.5 μM, respectively.     

Bioactive meroterpenoids and alkaloids from the fungus Eurotium chevalieri

Five new meroterpenoids, chevalones A-D (1-4), aszonapyrone B (8), and a new sequiterpene alkaloid, eurochevalierine (5), together with four known compounds, sequiterpene (6), terpenoid pyrrolobenzoxazine named CJ-12662 (7), meroterpenoid, aszonapyrone A (9), and ergosterol were isolated from the fungus Eurotium chevalieri. The structures were established on the basis of spectroscopic evidence. The configurations of 1 and 5 were determined by X-ray analysis. The biosynthetic pathway of 1-3, 8, and 9 were proposed. Chemical transformation of aszonapyrone A (9) was also studied. Compounds 4, 5, and 7 exhibited antimalarial activity against Plasmodium falciparum, while 3, 5, and 7 showed antimycobacterial activity against Mycobacterium tuberculosis. In addition, compounds 2-7 showed cytotoxicity against cancer cell lines.     

Polyhydroxylated steroids from the octocoral Isis hippuris

The specimens for previous studies on the secondary metabolites of the Formosan octocoral Isis hippuris were all collected at Green Island. In the course of our studies on bioactive compounds from marine organisms, the acetone-solubles of the Formosan octocoral I. hippuris collected at Orchid Island has led to the isolation of six new polyoxygenated steroids (1-6), along with a known compound 7. Compound 6 possesses a new type of steroid side chain moiety. The structures of these compounds were determined on the basis of their spectroscopic and physical data. The anti-HCMV (human cytomegalovirus) activity and cytotoxicity against selected cell lines of 1-7 were evaluated. Compound 3 exhibited inhibitory activity against HCMV, with an EC₅₀ values of 2.0 μg/mL, respectively. Compound 7 displayed cytotoxicity against P-388 and A-549 cell lines with ED₅₀ values of 3.2 and 3.86 μg/mL, respectively.     

New oxygenated diterpenes from an Australian nudibranch of the genus Chromodoris

Chemical analysis of a chromodorid nudibranch has provided two new diterpene metabolites 1 and 2 together with the known metabolites 3-6. In an NMR study, the dialdehyde metabolite 1 underwent facile conversion to cyclic hemiacetals 8-9 on exposure to methanol, a reaction that mimics chemical conversions that may occur during the isolation of some diterpenes from molluscs and sponges. Compounds 1, 2, 5 and 8 showed moderate cytotoxicity against P388 cells (IC₅₀=1.2-4.1 μg/mL).