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).     

Modiolin and phthalide derivatives from the endophytic fungus Microsphaeropsis arundinis PSU-G18

One new modiolin, microsphaerodiolin (1), and seven new phthalides, microsphaerophthalides A-G (2-8), together with 12 known compounds were isolated from the endophytic fungus Microsphaeropsis arundinis PSU-G18. Their structures were elucidated by spectroscopic methods. The new 3-oxygenated phthalides are rare natural products. The known 1-(2,5-dihydroxyphenyl)-2-buten-1-one exhibited significant antifungal activity against Microsporum gypseum SH-MU-4 with an MIC value of 8 μg/mL, moderate antimalarial activity with an IC₅₀ value of 9.63 μg/mL and strong radical scavenging potency with the IC₅₀ value of 0.018 mg/mL. The new compounds 2 and 6 showed moderately antifungal activity against M. gypseum SH-MU-4 and Cryptococcus neoformans, respectively, with equal MIC values of 64 μg/mL.     

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.     

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.     

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).     

Zyzzyanone A, a novel pyrrolo[3,2-f]indole alkaloid from the Australian marine sponge Zyzzya fuliginosa

A new dipyrroloquinone, zyzzyanone A 1, having a pyrrolo[3,2-f]indole-4,8(1H,7H)-dione skeleton, was isolated from the Australian marine sponge Zyzzya fuliginosa, along with the known pyrroloquinoline alkaloids, makaluvamines C, E, G, H, and L, and damirones A and B. The structure of 1 was determined by spectroscopic data. Zyzzyanone A 1 shows moderate cytotoxic activity against mouse Ehrlich carcinoma cells (IC₅₀ 25 μg/mL), inhibits the cell division of fertilized sea urchin eggs at a concentration of 25 μg/mL, and exhibits UV-A and UV-B absorbing activity.     

An asymmetric ent-kauranoid dimer from Isodon rubescens var. lushanensis

A novel asymmetric ent-kauranoid dimer, lushanrubescensin J (1), was isolated from Isodon rubescens var. lushanensis. Its structure was elucidated by the spectroscopic evidences. The stereochemistry was confirmed by the single crystal X-ray diffraction of its tetraacetate. Compound (1) exhibited potent inhibitory activity against K562 cells with IC₅₀ = 0.93 μg/mL.     

Torrubiellutins A-C, from insect pathogenic fungus Torrubiella luteorostrata BCC 12904

Investigation of the insect pathogenic fungus Torrubiella luteorostrata led to the isolation of three new macrocyclic torrubiellutins A-C (1-3) and the known pyrone diterpene 4. Structures were elucidated by spectroscopic data including 1D, 2D NMR, and MS spectral data. The absolute stereochemistry was determined by chemical means using Mosher reactions and Marfey's reagent, together with NOESY spectral data. Torrubiellutin C showed biological activities against KB, MCF-7, NCI-H187, and Vero cell lines with IC₅₀ varying from 0.78 to 4.36 μg/mL, while compound 4 exhibited antimalaria and anti-inflammatory activity with IC₅₀ values of 3.49 and 1.21 μg/mL, respectively.     

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).     

N-Hydroxypyridone alkaloids,chromone derivatives,and tetrahydroxanthones from the scale-insect pathogenic fungus Orbiocrella sp. BCC 33248

Six new compounds, an N-hydroxypyridone glucoside, orbiocrellin A (1), its aglycone orbiocrellin B (2), chromone glucosides 3 and 4, a dihydrochromone 5a/5b, and a chromone 6, were isolated from the scale-insect pathogenic fungus Orbiocrella sp. BCC 33248. Orbiocrellin A (1) exhibited antimalarial activity against Plasmodium falciparum K1 (IC₅₀ 3.1 μg/mL) while it was non-cytotoxic. In contrast, orbiocrellin B (2) showed both antimalarial (IC₅₀ 2.1 μg/mL) and cytotoxic (NCI-H187 cells, IC₅₀ 0.70 μg/mL) activities.     

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).     

Dihydroanthracenone metabolites from the endophytic fungus Diaporthe melonis isolated from Annona squamosa

Chemical investigation of the endophytic fungus Diaporthe melonis, isolated from Annona squamosa, yielded two new dihydroanthracenone atropodiastereomers, diaporthemins A (1) and B (2), together with the known flavomannin-6,6′-di-O-methyl ether (3). The structures of the new compounds were established on the basis of extensive 1D and 2D NMR spectroscopy, as well as by high resolution mass spectrometry and by CD spectroscopy. Compounds 1–3 were tested for their antimicrobial activity against a multi-resistant clinical isolate of Staphylococcus aureus 25697, a susceptible reference strain of S. aureus ATCC 29213 and against Streptococcus pneumoniae ATCC 49619. Compound 3 strongly inhibited S. pneumonia growth with a MIC value of 2 μg/mL, and showed moderate activity against the S. aureus multi-resistant clinical isolate and susceptible reference strain (MIC 32 μg/mL), whereas 1 and 2 were not active against the tested strains.     

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).     

Synthesis and characterization of glycoconjugate tin(IV) complexes: In vitro DNA binding studies, cytotoxicity, and cell death

New glycosyl derived ligand and its complexes, with SnCl₄·5H₂O (1) and (CH₃)₂SnCl₂(2) were synthesized and characterized by spectroscopic (IR, ¹H, ¹³C, and ¹¹⁹Sn NMR, UV-vis, ESI-MS) and analytical methods. Interaction studies of 1 and 2 with CT DNA were studied by using various biophysical techniques, which showed high binding affinity of 2 with CT DNA. In vitro cytotoxicity of complexes 1 and 2 were evaluated against different human cancer cell lines of different histological origins by employing SRB Assay. The organotin(IV) complex 2 exhibited remarkable activity against DWD (oral cancer) cell lines with GI₅₀ values <10 μg/ml. Complex 2 induced apoptosis of DWD cell line at a very low concentration of 1-4 μg/mL.     

Antimalarial and antituberculosis substances from Streptomyces sp. BCC26924

Two new carbazomycin dimers (6 and 7) and 3-hydroxy-1,2-dimethyl-2,3-dihydro-1H-carbazol-4-one (9) together with six known compounds, carbazomycins A-D, cyclomarin C, and pimprinine have been isolated from Streptomyces sp. BCC26924. Carbazomycins B, C, and cyclomarin C exhibited antimalarial activity (against Plasmodium falciparum, K1 multi-drug resistant strain) with IC₅₀ in a range of 0.24-2.37 μg/mL. Cyclomarin C exhibited anti-TB activity with a minimum inhibitory concentration value of 0.10 μg/mL, while carbazomycin D, compound 7, and pimprinine displayed MIC values in a range of 12.5-25.0 μg/mL. In addition, compounds 2, 5, 6, and 7 showed weak cytotoxicity against cancerous (MCF-7, KB, NCI-H187) and non-cancerous (Vero) cells.     

Triterpenoids from Cedrela sinensis

Twenty-three new triterpenoids (1-23), all having an apotirucallane skeleton, were isolated from the seeds, leaves, and stems of Cedrela sinensis (Meliaceae). Their structures were determined by 2D NMR experiments, X-ray crystallographic analysis, and chemical methods. These triterpenoids showed a moderate cytotoxic activity against P-388 murine leukemia cells (IC₅₀ 0.26-9.9 μg/mL).     

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.     

Kehokorins A-C, novel cytotoxic dibenzofurans isolated from the myxomycete Trichia favoginea var. persimilis

Kehokorins A (1)-C (3), three novel dibenzofurans, have been isolated from field-collected fruit bodies of the myxomycete, Trichia favoginea var. persimilis, and their structures were elucidated by spectral data. Kehokorin A (1) was a α-l-rhamnopyranoside of kehokorin B (2), while kehokorin C (3) was a 1-demethoxy analog of 2. Kehokorin A (1) was cytotoxic against HeLa cells with an IC₅₀ value of 1.5 μg/mL.     

Saccharonol B,a new cytotoxic methylated isocoumarin from Saccharomonospora azurea

From an antimicrobial gram-positive actinomycete strain of Saccharomonospora azurea (MTCC11714) isolated from high altitude soil of Kargil (J&K, India), a new isocoumarin saccharonol B (2) along with two known compounds viz. saccharonol A (1) and piericidin A₃ (3) was isolated and characterized. The structure of the new compound was established based on extensive 2D-NMR data. Saccharonol B (2) exhibited mild antimicrobial activity against a standard panel of microorganisms Staphylococcus aureus ATCC 29213, Candida albicans ATCC 90028, and Aspergillus fumigatus MTCC 1811 with MIC values in the range of 128–248 μg/mL. Saccharonol B (2) and piericidin A₃ (3) showed selective cytotoxic activity against human pancreatic carcinoma cell line (MIAPaCa-2) with IC₅₀ values of 9 and 8 μM, respectively. Mechanistic studies indicated that saccharonol B (2) arrests S-phase of the cell cycle and causes dose-dependent loss of mitochondrial potential in MIAPaCa-2 cells.     

Absolute configuration and antibiotic activity of neosartorin from the endophytic fungus Aspergillus fumigatiaffinis

Neosartorin (1) was isolated from the endophytic fungus Aspergillus fumigatiaffinis. The absolute configuration of 1, including both axial and central chirality elements, was established as (aR,5S,10R,5′S,6′S,10′R) for the first time on the basis of its electronic circular dichroism (ECD) spectra aided with TDDFT–ECD calculations. Neosartorin (1) exhibited substantial antibacterial activity against a broad spectrum of Gram-positive bacterial species including staphylococci, streptococci, enterococci, and Bacillus subtilis with minimal inhibitory concentrations in the range of 4–32 μg/mL. When the toxicity of 1 against eukaryotic cells was measured using a panel of different cancer cell lines such as HELA and BALB/3T3, the average IC₅₀ values exceeded 32 μg/mL.