Fascioquinols A-F: bioactive meroterpenes from a deep-water southern Australian marine sponge, Fasciospongia sp.

Chemical investigation of a southern Australian deep-water marine sponge, Fasciospongia sp., returned the new meroterpene sulfate fascioquinol A (1) together with a series of acid mediated hydrolysis/cyclization products, fascioquinols B (2), C (3) and D (4), and strongylophorine-22 (5). Additional co-metabolites include the new meroterpenes fascioquinol E (6) and fascioquinol F (8), together with the known sponge metabolite geranylgeranyl 1,4-hydroquinone (7). Structures were assigned to 1-8 on the basis of detailed spectroscopic analysis, chemical interconversion, mechanistic and biosynthetic considerations, and literature comparisons. The known 1,4-hydroquinone 7 was identified as the dominant cytotoxic principle in the Fasciospongia sp. extract, with selective inhibitory activity against gastric adenocarcinoma (AGS, IC₅₀ 8 μM) and neuroblastoma (SH-SY5Y, IC₅₀ 4 μM) cell lines. By contrast, while the fascioquinols displayed little or no inhibitory activity towards human cell lines, 1 and 2 displayed promising Gram-positive selective antibacterial activity towards Staphylococcus aureus (IC₅₀ 0.9-2.5 μM) and Bacillus subtilis (IC₅₀ 0.3-7.0 μM).     

Polyketides from the mangrove-derived endophytic fungus Acremonium strictum

Five new polyketide derivatives, 6′-hydroxypestalotiopsone C (1), acropyrone (2), bicytosporone D (3), waol acid (4), and pestalotiopene C (5), together with seven known metabolites (6–12), were obtained from extracts of the endophytic fungus Acremonium strictum, isolated from the mangrove tree Rhizophora apiculata. The structures of the isolated compounds were elucidated on the basis of comprehensive NMR and MS analysis. Compounds 6, 7, and 9 showed moderate cytotoxic activity against human cisplatin-sensitive (IC₅₀ values 27.1, 76.2, and 8.3 μM, respectively) and resistant A2780 cell lines (IC₅₀ values 12.6, 30.1, and 19.0 μM, respectively), whereas only 9 exhibited antibacterial activity against Staphylococcus aureus (MIC value 14.3 μM).     

Isolation of secondary metabolites from Hortia oreadica (Rutaceae) leaves through high-speed counter-current chromatography

High-speed counter-current chromatography (HSCCC) with a two-phase solvent system (hexane–ethanol–acetonitrile–water 10:8:1:1, v/v) was applied to examine the leaves of Hortia oreadica, which afforded the known limonoid guyanin (1), the alkaloids rutaecarpin (2) and dictamnine (6), the dihydrocinnamic acid derivatives methyl 5,7-dimethoxy-2,2-dimethyl-2H-1-benzopyran-6-propanoate (3), 5,8-dimethoxy-2,2-dimethyl-2H-1-benzopyran-6-propanoic acid (4), together with the new E-3,4-dimethoxy-α(3-hydroxy-4-carbomethoxyphenyl)cinnamic acid (5). The recovery of compounds 1–6 was determined by comparison with LC-atmospheric pressure chemical ionization MS/MS data: 66.2%, 93.1%, 102.5%, 101.2%, 99.0% and 84.9%, respectively. Compound 3 showed IC₅₀ of 23.6 μM against Plasmodium falciparum and 15.6 μM against Trypanosoma brucei rhodesienses and was not toxic to KB cells (IC₅₀ > 100 μM).     

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).     

Two novel diterpenoids from Isodon rubescens var. lushanensis

Two novel diterpenoids, luanchunins A (1) and B (2), along with their precursor, kamebakaurin (3), had been isolated from the stems and leaves of Isodon rubescens var. lushanensis. Their structures were elucidated on the basis of extensive spectroscopic analyses. Compounds 1 and 2 showed potent cytotoxic activity against HL-60 with IC₅₀ values of 4.81 μM and 3.52 μM, respectively. Plausible pathways for the biosynthesis of 1 and 2 were also postulated.     

Isolation, structure elucidation and bioactivity of schischkiniin, a unique indole alkaloid from the seeds of Centaurea schischkinii

Reversed-phase HPLC analysis of the methanol extract of the seeds of Centaurea schischkinii afforded a novel indole alkaloid, named schischkiniin (1), together with four lignans, arctiin (2), matairesinoside (3), matairesinol (4), and arctigenin (5), and three flavonoids, astragalin (6), afzelin (7) and apigenin (8). While the structure of schiskiniin (1) was established unequivocally by UV, HRFABMS and a series of 1D and 2D NMR analyses, all known compounds were readily identified by comparison of their spectroscopic data with literature data. The free radical scavenging properties of these compounds were assessed using the DPPH assay, and their general toxicity and cytotoxicity were evaluated, respectively, by brine shrimp lethality and MTT cytotoxicity assays with CaCo-2 colon cancer cell lines. Arctigenin (5) exhibited promising in vitro anticancer activity (IC₅₀=7 μM) while with schischkiniin (1) the activity was of moderate level (IC₅₀=76 μM).     

Lissoclibadins 1-3, three new polysulfur alkaloids, from the ascidian Lissoclinum cf. badium

Three new polysulfur alkaloids, lissoclibadins 1 (1)-3 (3), were isolated from the ascidian Lissoclinum sp. (cf. L. badium Monniot, F. and Monniot, C., 1996). The structures of 1-3 were assigned on the basis of their spectral data, and the computational modeling study was utilized for 1. Compound 1 had a trimeric structure of three identical aromatic anime moieties connected through two sulfide and a disulfide bonds. Compounds 2 and 3 were dimeric structures of the same unit as that of 1 connected through a sulfide and disulfide bonds (2) and two sulfide bonds (3). Compounds 1 and 2 inhibited the growth of the marine bacterium Ruegeria atlantica (15.2 mm at 20 μg/disk and 12.2 mm at 5 μg/disk, respectively) and 2 showed antifungal activity to Mucor hiemalis (13.8 mm at 50 μg/disk). Compounds 1-3 were cytotoxic against HL-60 (IC₅₀=0.37, 0.21, and 5.5 μM, respectively).     

Sphenalactones A-D, a new class of highly oxygenated trinortriterpenoids from Schisandra sphenanthera

Four novel highly oxygenated trinortriterpenoids, sphenalactones A-D (1-4), were isolated from the leaves and stems of Schisandra sphenanthera and their structures were elucidated by extensive analysis of 1D and 2D NMR data. Compounds 1-4 featured a C₂₇ backbone and showed anti-HIV-1 activity with EC₅₀ values in the range of 35.5-89.1 μg/mL with low cytotoxicity against C8166 cells (CC₅₀ > 200 μg/mL).     

Montamine, a unique dimeric indole alkaloid, from the seeds of Centaurea montana (Asteraceae), and its in vitro cytotoxic activity against the CaCo2 colon cancer cells

Reversed-phase HPLC analysis of the methanol extract of the seeds of Centaurea montana afforded a flavanone, montanoside (4), six epoxylignans, berchemol (7), berchemol 4′-O-β-d-glucoside (5), pinoresinol (10), pinoresinol 4-O-β-d-glucoside (8), pinoresinol 4,4′-di-O-β-d-glucoside (6), pinoresinol 4-O-apiose-(1→2)-β-d-glucoside (9), two quinic acid derivatives, trans-3-O-p-coumaroylquinic acid (1), cis-3-O-p-coumaroylquinic acid (2), and eight indole alkaloids, tryptamine (3), N-(4-hydroxycinnamoyl)-5-hydroxytryptamine (11), cis-N-(4-hydroxycinnamoyl)-5-hydroxytryptamine (12), centcyamine (16), cis-centcyamine (17), moschamine (13), cis-moschamine (14) and a dimeric indole alkaloid, montamine (15). While the structures of two new compounds, montanoside (4) and montamine (15), were established unequivocally by UV, IR, MS and a series of 1D and 2D NMR analyses, all known compounds were identified by comparison of their spectroscopic data with literature data. The antioxidant properties of these compounds were assessed by the DPPH assay, and their toxicity towards brine shrimps and cytotoxicity against CaCo-2 colon cancer cells were evaluated by the brine shrimp lethality and the MTT cytotoxicity assays, respectively. The novel dimer, montamine (15), showed significant in vitro anticolon cancer activity (IC₅₀=43.9 μM) while that of the monomer, moschamine (13), was of a moderate level (IC₅₀=81.0 μM).     

Carbamidocyclophanes F and G with anti-Mycobacterium tuberculosis activity from the cultured freshwater cyanobacterium Nostoc sp.

Two new (1 and 2) and three known (3–5) carbamidocyclophanes were isolated from a cultured freshwater cyanobacterium Nostoc sp. (UIC 10274) obtained from a sample collected at Des Plaines, Illinois. Their planar structures and stereoconfigurations were determined by extensive spectroscopic analysis including 1D/2D NMR experiments, HRESIMS as well as CD spectroscopy. Carbamidocyclophane F (1) showed potent anti-Mycobacterium tuberculosis activity in the microplate Alamar blue assay and low-oxygen-recovery assay with MIC values of 0.8 and 5.4 μM, respectively. Carbamidocyclophane F (1) also displayed antimicrobial activities against the gram positive bacteria Staphylococcus aureus and Enterococcus faecalis with MIC values of 0.1 and 0.2 μM, respectively. Carbamidocyclophane F (1) and Carbamidocyclophane G (2) both showed antiproliferative activity against MDA-MB-435 and HT-29 human cancer cell lines with IC₅₀ values in the range from 0.5 to 0.7 μM.     

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.     

Novel sesquiterpenes and norergosterol from the soft corals Nephthea erecta and Nephtheachabroli

Chemical investigations on the acetone extract of the Formosan soft coral Nephthea erecta have afforded a new calamenene-type sesquiterpene with a mercaptan group at C-15, erectathiol (1), and a previously reported sesquiterpenoid, (+)-trans-calamenene (2). A novel sec-germacrane sesquiterpene (3), along with a novel norergosterol, chabrosterol (4), possessing a 19-norergostane skeleton, was isolated from the other soft coral Nephthea chabroli. The structures of these metabolites were elucidated through extensive spectroscopic analyses. In vitro anti-inflammatory activity of 1 and 4 (10 μM) significantly reduced the levels of the iNOS protein (58.0 ± 6.5% and 12.4 ± 2.9%) and COX-2 protein (108.7 ± 4.5% and 45.2 ± 5.4%). In addition, metabolite 1 (166 μg/disk) exhibited antimicrobial activities against a small panel of bacterial strains.     

Proteasome-inhibitory and cytotoxic constituents of Garcinia lateriflora: absolute configuration of caged xanthones

A new biflavonoid (1), a new xanthone enantiomer (2), five new caged xanthones (3-7), and several known compounds were isolated from the stem bark of Garcinia lateriflora, collected in Indonesia. The structures of the new compounds were determined by analysis of spectroscopic data, and the absolute configuration of the caged xanthones was shown for the first time at carbons 5, 7, 8, 8a, 10a, and 27, by analysis of COSY and NOESY NMR and ECD spectra. The biflavonoids exhibited proteasome-inhibitory activity, and the known compound, morelloflavone (8) was found to have the greatest potency (IC₅₀=1.3 μM). The caged xanthones were cytotoxic toward HT-29 cells, with the known compound, morellic acid (10) being the most active (ED₅₀=0.36 μM). However, when tested in an in vivo hollow fiber assay, it was inactive at the highest dose tested (20 mg/kg).     

Synthesis, characterization and reactivity of tribenzylphosphine rhodium and iridium complexes

New rhodium and iridium complexes, with the formula [MCl(PBz₃)(cod)] [M = Rh (1), Ir (2)] and [M(PBz₃)₂(cod)]PF₆ [M = Rh (3), Ir (4)] (cod = 1,5-cyclooctadiene), stabilized by the tribenzylphosphine ligand (PBz₃) were synthesized and characterized by elemental analysis and spectroscopic methods. The molecular structures of 1 and 2 were determined by single-crystal X-ray diffraction. The addition of pyridine to a methanol solution of 1or 2, followed by metathetical reaction with NH₄PF₆, gave the corresponding derivatives [M(py)(PBz₃)(cod)]PF₆ [M = Rh (5), Ir (6)]. At room temperature in CHCl₃ solution, 4 converted spontaneously to the ortho-metallated complex [IrH(PBz₃)(cod){η²-P,C-(C₆H₄CH₂)PBz₂}]PF₆ (7) as a mixture of cis/trans isomers via intramolecular C-H activation of a benzylic phenyl ring. The reaction of 3 or 4 with hydrogen in coordinating solvents gave the dihydrido bis(solvento) derivative [M(H)₂(S)₂(PBz₃)₂]PF₆ (M = Rh, Ir; S = acetone, acetonitrile, THF), that transformed into the corresponding dicarbonyls [M(H)₂(CO)₂(PBz₃)₂]PF₆ by treatment with CO. Analogous cis-dihydrido complexes [M(H)₂(THF)₂(py)(PBz₃)₂]PF₆ (M = Rh, Ir) were observed by reaction of the py derivatives 5 and 6 with H₂.     

Trisorbicillinone A, a novel sorbicillin trimer, from a deep sea fungus, Phialocephala sp. FL30r

A novel sorbicillin trimer, trisorbicillinone A (1), was isolated from a deep sea fungus, Phialocephala sp. FL30r. The structure and relative stereochemistry of 1 were determined based on spectroscopic methods. Trisorbicillinone A (1) showed cytotoxicity against P388 and HL60 cells with the IC₅₀ value of 9.10 and 3.14 μM, respectively.     

Neosappanone A, a xanthine oxidase (XO) inhibitory dimeric methanodibenzoxocinone with a new carbon skeleton from Caesalpinia sappan

A novel dimeric methanodibenzoxocinone, named neosappanone A (1), possessing a unique unprecedented novel carbon framework, has been isolated from the heartwood of Caesalpinia sappan L. of Vietnam, and its structure was elucidated on the basis of spectroscopic analysis. Neosappanone A (1) competitively inhibited xanthine oxidase in a concentration-dependent manner (IC₅₀, 29.7 μM; K_i, 16.3 μM).     

Synthesis and molecular structures of dinuclear complexes with 1,2-dihydro-1,2-diphenyl-naphtho[1,8-c,d]1,2-diphosphole as a bridging ligand

A bisphosphine in which a PhP-PPh bond bridges 1,8-positions of naphthalene, 1,2-dihydro-1,2-diphenyl-naphtho[1,8-cd]-1,2-diphosphole (1), was used as a bridging ligand for the preparation of dinuclear group 6 metal complexes. Free trans-1, a more stable isomer having two phenyl groups on phosphorus centers mutually trans with respect to a naphthalene plane, was allowed to react with two equivalents of M(CO)₅(thf) (M = W, Mo, Cr) at room temperature to give dinuclear complexes (OC)₅M(μ-trans-1)M(CO)₅ (M = W (2a), Mo (2b), Cr (2c)). The preparation of the corresponding dinuclear complexes bridged by the cis isomer of 1 was also carried out starting from the free trans-1 in the following way. Mono-nuclear complexes M(trans-1)(CO)₅ (M = W (3a), Mo (3b), Cr (3c)) which had been prepared by a reaction of trans-1 with one equivalent of the corresponding M(CO)₅(thf) (M = W, Mo, Cr) complex, were heated in toluene, wherein a part of the trans-3a-c was converted to their respective cis isomer M(cis-1)(CO)₅. Each cis trans mixture of the mono-nuclear complexes 3a-c was treated with the corresponding M(CO)₅(thf) to give a cis trans mixture of the respective dinuclear complexes 2a-c. The cis isomer of the ditungsten complex 2a was isolated, and its molecular structure was confirmed by X-ray analysis, showing a shorter W?W distance of 5.1661(3) Å than that of 5.8317(2) Å in trans-2a.     

Abiesanordines A-N: fourteen new norditerpenes from Abies georgei

Fourteen new norditerpenoids (abiesanordines A-N, 1-14), including a novel podocarpene bearing a rare enolic structure (abiesanordine A, 1), were isolated from Abies georgei together with eight known ones. Their structures were determined mainly by detailed analysis of 1D and 2D NMR spectroscopic data including HSQC, DQF COSY, HMBC, and NOESY. All the isolates were tested for inhibitory activities against LPS-induced NO production in RAW264.7 macrophages, abiesanordine I (9) showed the strongest activity with the IC₅₀ value of 17.0 μg/mL. Furthermore, it exhibited no cytotoxicity against RAW264.7 macrophages under the concentration of 50 μg/mL.     

Chlorahololides C-F: a new class of potent and selective potassium channel blockers from Chloranthus holostegius

Four unusually fused polycyclic sesquiterpenoid dimers, chlorahololides C-F (1-4), were isolated from the whole plant of Chloranthus holostegius. Their structures and absolute configurations were established by spectroscopic methods, including 2D NMR and CD spectra. Chlorahololides C-F (1-4) exerted potent and selective inhibition on the delayed rectifier (I_K) K⁺ current with the IC₅₀ values of 3.6±10.1, 2.7±0.3, 27.5±5.1 and 57.5±6.1 μM, respectively.     

Synthesis and cytotoxicity studies of new dimethylamino-functionalised and heteroaryl-substituted titanocene anti-cancer drugs

From the carbolithiation of N,N-dimethylamino fulvene (3a) and different ortho-lithiated heterocycles (furan, thiophene and N-methylpyrrole), the corresponding lithium cyclopentadienide intermediate (4a-c) was formed. These three lithiated intermediates underwent a transmetallation reaction with TiCl₄ resulting in dimethylamino-functionalised titanocenes 5a-c. When these titanocenes were tested against LLC-PK cells, the IC₅₀ values obtained were of 240, and 28 μM for titanocenes 5a and 5b, respectively. The most cytotoxic titanocene 5c with an IC₅₀ value of 5.5 μM is found to be almost as cytotoxic as cis-platin, which showed an IC₅₀ value of 3.3 μM, when tested on the LLC-PK cell line, and titanocene 5c is approximately 400 times better than titanocene dichloride itself.