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.     

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).     

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.     

Antimicrobial sesquiterpenes from the Chinese medicinal plant, Chloranthus angustifolius

Two new eudesmane-type sesquiterpenes, 9α-hydroxycurcolonol (1) and 3α-hydroxy-4-deoxy-5-dehydrocurcolonol (2), along with nine known sesquiterpenes (3–11), were isolated from the roots of Chloranthus angustifolius. The antimicrobial activities of compounds 1–11 were evaluated against five bacteria and six fungal strains. Compounds 6–11 showed potent activities against Candida albicans with MIC values ranging from 4 to 8 μg/mL. The structures of the two new compounds 1 and 2 were established by a detailed analysis of their NMR and mass spectroscopic data.     

Banchromene and other secondary metabolites from the endophytic fungus Fusarium sp. obtained from Piper guineense inhibit the motility of phytopathogenic Plasmopara viticola zoospores

A new chromene, (S)-banchromene (1), together with seven known compounds, ergosterol, beauvericin (2), fusaproliferin (3), radicinin (4), poly(3-hydroxybutyric acid) (PHB, 5), N-methylpyrrolidone and an inseparable mixture of isochromene derivatives 6a, 6b, were isolated from a culture of Fusarium sp. strain CAMKT24b1, an endophytic fungus from the leaves and twigs of Piper guineense (Piperaceae). The structures of these metabolites were elucidated on the basis of their spectroscopic data; the absolute configuration of 1 was determined by ab initio-calculation of the optical rotation. In tests with the zoospores of the grapevine downy mildew pathogen Plasmopara viticola, compounds 1–4 showed moderate to high levels of motility-impairing activity at concentrations as low as 2.5 μg/mL. Compound 2 was the most active, exhibiting both motility-halting and lytic activities. Furthermore, compounds 2 and 3 displayed significant cytotoxic activity against brine shrimp larvae (Artemia salina) at 10 μg/mL. This is the first report on motility inhibitory and lytic activities of metabolites from an endophytic Fusarium species against the zoospores of the downy mildew pathogen P. viticola.     

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.     

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.     

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.     

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).     

Oxygenated xanthones and biflavanoids from the twigs of Garcinia xanthochymus

Three new xanthones, xanthochymones A–C (1–3), together with six known compounds including two xanthones, three biflavanoids, and one mellein derivative are isolated from the methanol extract of the twigs of Garcinia xanthochymus. Their structures are identified on the basis of their spectroscopic data. Compound 3 displays moderate antibacterial activity against Staphylococcus aureus while compounds 2 and 3 are weakly active against methicillin-resistant S. aureus.     

Angumycinones A and B,two new angucyclic quinones from Streptomyces sp. KMC004 isolated from acidic mine drainage

Two new angucyclic quinones, angumycinones A (1) and B (2) and six known angucyclinone analogues (3–8) were isolated from a liquid culture extract of the Streptomyces sp. KMC004 strain from acidic coal mine drainage. The structures of these compounds were established using extensive spectroscopic data analyses, including NMR, HRFABMS, UV, CD, and X-ray crystallography. Compounds 1–8 were tested for antimicrobial activity against ten pathogenic microbial or fungal strains. Angumycinone B (2) exhibited antimicrobial activity against Micrococcus luteus, Enterococcus hirae, and methicillin-resistant Staphylococcus aureus (MRSA) with minimum inhibitory concentration values of 0.78, 1.56, and 12.5 μg/mL, respectively.     

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).     

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).     

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.     

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.     

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.     

Musanahol: a new aureonitol-related metabolite from a Chaetomium sp.

Two antibacterial furano-polyenes, (−)-musanahol (1) and 3-epi-aureonitol (5), and a fatty acid, linoleic acid (8) were isolated from the laboratory cultures of a Chaetomium sp. accessed from tomato fruits, and grown on YMG medium (yeast extract, glucose, malt extract and water) at pH 5.8-6.0. The structure of compound 1, a new furano-polyene, was elucidated by spectroscopic methods that include extensive 2D NMR experiments, double resonance experiments, Mosher's method and PM3 calculations. (−)-Musanahol (1) and 3-epi-aureonitol (5) were present in the culture filtrate of the fungus. 3-epi-Aureonitol (5) completely inhibited the growth of Streptococcus pyogenes at 15.63 μg/mL and Escherichia coli, Staphylococcus aureus, Salmonella choleraesuis and Corynebacterium diphtheriae at 31.25 μg/mL, whereas (−)-musanahol (1) lacked the antimicrobial potency of compound 5 in spite of the similarities in their structures. Linoleic acid (8) was isolated from the mycelia of the fungus; it inhibited the growth of S. aureus and Bacillus subtilis at a minimum concentration of 15.62 μg/mL.     

Two novel polycyclic spiro lignans from Gymnotheca involucrata

Two novel lignans, gymnothespirolignans A (1) and B (2), possessing a rare polycyclic spiro skeleton, were isolated from the endemic plant of Gymnotheca involucrata Pei. Their structures were determined by spectroscopic evidences and the absolute configurations were confirmed by single crystal X-ray diffraction analysis. Compounds 1 and 2 showed promising antiviral activities against RSV with an IC₅₀ value of 31.87 and 17.51 μM, respectively.     

Six insecticidal isoryanodane diterpenoids from the bark and twigs of Itoa orientalis

Four rare isoryanodane diterpenoids namely itols A-D (1-4) and two isoryanodane glucosides (5 and 6) were isolated from the bark and twigs of Itoa orientalis. Their structures were determined by NMR and MS techniques and the structure of 1 was confirmed by a single-crystal X-ray diffraction. These six diterpenoids obviously showed insecticidal activity against Spodoptera exigua, with LC₅₀ 28.62 ppm for 1 and 52.76 ppm for 2, respectively. In anti-inflammatory assay, compounds 1 and 4-6 showed anti-COX-2 activity, with inhibitory rates of 54.7-78.3% at 10 μM.     

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).