Secondary metabolites from an algicolous Aspergillus versicolor strain

Two new compounds, asperversin A (1) and 9ξ-O-2(2,3-dimethylbut-3-enyl)brevianamide Q (2), and nine known compounds, brevianamide K (3), brevianamide M (4), aversin (5), 6,8-di-O-methylnidurufin (6), 6,8-di-O-methylaverufin (7), 6-O-methylaverufin (8), 5α,8α-epidioxyergosta-6,22-dien-3β-ol (9), ergosta-7,22-diene-3β,5α,6β-triol (10), and 6β-methoxyergosta-7,22-diene-3β,5α-diol (11), were obtained from the culture of Aspergillus versicolor, an endophytic fungus isolated from the marine brown alga Sargassum thunbergii. The structures of these compounds were established by spectroscopic techniques. Compounds 4, 7 and 8 exhibited antibacterial activities against Escherichia coli and Staphyloccocus aureus, and 7 also showed lethality against brine shrimp (Artemia salina) with an LC₅₀ value of 0.5 μg/mL.     

Indole Diterpenoids and Isocoumarin from the Fungus,Aspergillus flavus,Isolated from the Prawn,Penaeus vannamei

Two new indole-diterpenoids (1 and 2) and a new isocoumarin (3), along with the known β-aflatrem (4), paspalinine (5), leporin B (6), α-cyclopiazonic acid (7), iso-α-cyclopiazonic acid (8), ditryptophenaline (9), aflatoxin B₁ (10), 7-O-acetylkojic acid (11) and kojic acid (12), were isolated from the fermentation broth of the marine-derived fungus, Aspergillus flavus OUCMDZ-2205. The structures of Compounds 1–12 were elucidated by spectroscopic analyses, quantum ECD calculations and the chemical method. New Compound 1 exhibited antibacterial activity against Staphylococcus aureus with a MIC value of 20.5 μM. Both new Compounds 1 and 2 could arrest the A549 cell cycle in the S phase at a concentration of 10 μM. Compound 1 showed PKC-beta inhibition with an IC₅₀ value of 15.6 μM. In addition, the absolute configurations of the known compounds, 4–6 and leporin A (6a), were also determined for the first time.     

Evaluation of Pyridoacridine Alkaloids in a Zebrafish Phenotypic Assay

Three new minor components, the pyridoacridine alkaloids 1-hydroxy-deoxyamphimedine (1), 3-hydroxy-deoxyamphimedine (2), debromopetrosamine (3), and three known compounds, amphimedine (4), neoamphimedine (5) and deoxyamphimedine (6), have been isolated from the sponge Xestospongia cf. carbonaria, collected in Palau. Structures were assigned on the basis of extensive 1D and 2D NMR studies as well as analysis by HRESIMS. Compounds 1–6 were evaluated in a zebrafish phenotype-based assay. Amphimedine (4) was the only compound that caused a phenotype in zebrafish embryos at 30 μM. No phenotype other than death was observed for compounds 1–3, 5, 6.     

Oxygenated Eremophilane- and Neolemnane-Derived Sesquiterpenoids from the Soft Coral Lemnalia philippinensis

Five sesquiterpene-related metabolites (1–5), including two new eremophilane-type compounds, philippinlins C and D (1 and 2) and a 4,5-seconeolemnane philippinlin E (3), were isolated from the organic extract of a Taiwanese soft coral Lemnalia philippinensis. The structures of the new metabolites were determined on the basis of extensive spectroscopic analysis and by comparison of NMR data with those of related metabolites. Compound 3 was suggested to be derived from the neolemnane skeleton.     

Reduced height alleles (Rht) and Hagberg falling number of wheat

Near-isogenic lines varying for alleles for reduced height (Rht) and photoperiod insensitivity (Ppd-D1) in cv. Mercia (2005/6–2010/11; rht (tall), Rht-B1b, Rht-D1b, Rht-B1c, Rht8c+Ppd-D1a, Rht-D1c, Rht12) and cvs Maris Huntsman and Maris Widgeon (2007/8–2010/11; rht (tall), Rht-B1b, Rht-D1b, Rht-B1c, Rht-B1b+Rht-D1b, Rht-D1b+Rht-B1c) were compared at one field site, but within different systems (‘organic’, O, 2005/6–2007/8 v. ‘intensive’, I, 2005/6–2010/11). Further experiments at the site (2006/7–2008/9) compared 64 lines of a doubled-haploid (DH) population [Savannah (Rht-D1b) × Renesansa (Rht-8c+Ppd-D1a)]. Gibberellin (GA) insensitive dwarfing alleles (Rht-B1b; Rht-B1c; Rht-D1b; Rht-D1c) could reduce α-amylase activity and/or increase Hagberg falling number (HFN) but effects depended greatly on system, background and season. Only Rht-B1c increased grain dormancy despite producing plants taller than Rht-D1c. The GA-sensitive Rht8c+Ppd-D1a in Mercia was associated with reduced HFN but analysis of the DH population suggested this was more closely linked with Ppd-D1a, rather than Rht8c. The GA-sensitive severe-dwarfing allele Rht12 was associated with reduced HFN. Instability in HFN over season tended to increase with degree of dwarfing. There was a negative association between mean grain weight and HFN that was in addition to effects of Rht and Ppd-D1 allele.     

Compatibility of entomopathogenic nematodes (Nematoda: Rhabditida) with registered insecticides for Spodoptera frugiperda (Smith, 1797) (Lepidoptera: Noctuidae) under laboratory conditions

The fall armyworm, Spodoptera frugiperda (Smith, 1797) (Lepidoptera: Noctuidae) is considered the main key pest of corn crops in Brazil. Entomopathogenic nematodes (EPNs) may be used to control this pest, applied together with other different entomopathogen agents or phytosanity products in the spraying mixture. Thus, the objective of work was to evaluate the compatibility of EPNs with different insecticides used of S. frugiperda control in laboratory conditions. Three species of EPNs (Heterorhabditis indica, Steinernema carpocapsae and Steinernema glaseri) and 18 insecticides registered to control of S. frugiperda in corn crops were tested. Compatibility of the insecticides with EPNs was evaluated by observing mortality and infectivity of infecting juveniles (IJs) 48 h after immersion in solution of the insecticide formulations. Among all insecticides tested, Lorsban™ (chlorpyrifos), Decis™ (deltamethrin), Match™ (lufenuron), Deltaphos™ (deltramethrin + triazophos), Dimilin™ (diflubenzuron), Stallion™ (gamacyhalothrin), Karate Zeon™ (lambdacyhalothrin) Tracer™ (spinosad), Vexter™ (chlorpyrifos), Galgotrin™ (cypermethrin), Certero™ (triflumuron), and Talcord™ (permethrin) were compatible (class 1) with the three nematode species tested under laboratory conditions.     

Four New Antibacterial Xanthones from the Marine-Derived Actinomycetes Streptomyces caelestis

Four new polycyclic antibiotics, citreamicin θ A (1), citreamicin θ B (2), citreaglycon A (3), and dehydrocitreaglycon A (4), were isolated from marine-derived Streptomyces caelestis. The structures of these compounds were elucidated by 1D and 2D NMR spectra. All four compounds displayed antibacterial activity against Staphylococcus haemolyticus, Staphylococcus aureus, and Bacillus subtillis. Citreamicin θ A (1), citreamicin θ B (2) and citreaglycon A (3) also exhibited low MIC values of 0.25, 0.25, and 8.0 μg/mL, respectively, against methicillin-resistant Staphylococcus aureus (MRSA) ATCC 43300.     

Cembrane Derivatives from the Soft Corals,Sinularia gaweli and Sinularia flexibilis

A new norcembranoidal diterpene, 1-epi-sinulanorcembranolide A (1), and a new cembranoidal diterpene, flexibilin D (2), were isolated from the soft corals, Sinularia gaweli and Sinularia flexibilis, respectively. The structures of new metabolites 1 and 2 were elucidated by spectroscopic methods, and compound 2 was found to significantly inhibit the accumulation of the pro-inflammatory iNOS and COX-2 proteins of the lipopolysaccharide (LPS)-stimulated RAW264.7 macrophage cells. In addition, S. flexibilis yielded a known cembrane, 5-dehydrosinulariolide (3); the structure, including its absolute stereochemistry, was further confirmed by single-crystal X-ray diffraction analysis.     

Occurrence and characterization of fungi and oomycetes transmitted via potting mixtures and organic manures

A study was conducted to investigate the most common fungal and oomycete pathogens introduced into farms in Oman via potting mixtures and organic manures. A total of 37 commercial types of potting mixtures (2 local and 35 imported from overseas), 4 commercial types of organic manures and 11 non-commercial types of organic manures were included in the study. Identification of the isolated species was based on morphological characteristics, except for the most common species which were further identified using sequences of the internal transcribed spacer region of the ribosomal DNA (ITS rDNA). Fusarium spp. (14%), Pythium aphanidermatum (3%), Alternaria spp. (5%), Helminthosporium spp. (5%) and Cladosporium spp. (3%) were recovered at different frequencies from samples of potting mixtures. Fusarium solani (40%) and Fusarium equiseti (47%) were recovered at high frequencies from samples of organic manures. Isolations from organic manures also yielded Pythium periplocum (7%), Rhizoctonia solani (7%), Fusarium lichenicola (7%), Helminthosporium spp. (27%) and Alternaria spp. (27%). Trichoderma spp., Penicillium spp., Aspergillus spp. and Rhizopus spp. were found to be common in samples of potting mixtures and organic manures. Investigating sensitivity to hymexazol among 9 isolates of F. equiseti and 13 isolates of F. solani revealed variations among different isolates. The EC₅₀ values ranged from 1 to over 1200 (avg. 192 μg ml⁻¹) for F. equiseti isolates and from 135 to 789 (avg. 324 μg ml⁻¹) for F. solani isolates, indicating presence of resistance to this important fungicide among some Fusarium isolates. This appears to be the first report of contamination with R. solani, P. periplocum, F. solani, F. equiseti and F. lichenicola of organic manures. This study appears to report for the first time F. lichenicola in Oman and appears to be the first report of occurrence of resistance to hymexazol among F. equiseti and F. solani isolates.     

Cytotoxic and Antibacterial Cembranoids from a South China Sea Soft Coral,Lobophytum sp

Chemical examination of a South China Sea soft coral Lobophytum sp. led to the isolation of three new α-methylene-γ-lactone-containing cembranoids, (1R*,3R*,4R*,14R*,7E,11E)-3,4-epoxycembra-7,11,15(17)-trien-16,14-olide (1), (1R*,7S*,14S*,3E,11E)-7-hydroperoxycembra-3,8(19),11,15(17)-tetraen-16,14-olide (2), and (1R*,7S*,14S*,3E,11E)-18-acetoxy-7-hydroperoxycembra-3,8(19),11,15(17)-tetraen-16,14-olide (3), along with eleven known analogues 4–14. The structures of the new compounds were elucidated through extensive spectroscopic analysis, including 1D and 2D NMR data. Compounds 1–3 exhibited moderate cytotoxic activity against the selected tumor cell lines. Moreover, 2 and 3 were found to be moderate inhibitors against the bacteria S. aureus and S. pneumoniae.     

Antibacterial Activities of a New Brominated Diterpene from Borneon Laurencia spp

In our continuous interest to study the diversity of halogenated metabolites of Malaysian species of the red algal genus Laurencia, we examined the chemical composition of five populations of unrecorded Laurencia sp. A new brominated diterpene, 10-acetoxyangasiol (1), and four other known metabolites, aplysidiol (2), cupalaurenol (3), 1-methyl-2,3,5-tribromoindole (4), and chamigrane epoxide (5), were isolated and identified. Isolated metabolites exhibited potent antibacterial activities against clinical bacteria, Staphylococcus aureus, Staphylococcus sp., Streptococcus pyogenes, Salmonella sp. and Vibrio cholerae.     

Actinomycetes mediated biochemical responses in tomato (Solanum lycopersicum) enhances bioprotection against Rhizoctonia solani

Six actinomycetes isolates, namely Streptomyces toxytricini vh6, Streptomyces flavotricini vh8, S. toxytricini vh22, Streptomyces avidinii vh32, Streptomyces tricolor vh85 and vh41, an isolate of an unknown species of Actinomycetales, were tested for their efficacy in protecting tomato (Solanum lycopersicum) against Rhizoctonia solani under green house conditions. Actinomycetes treated plants showed better growth in terms of high chlorophyll content, higher phenylalanine ammonia lyase (PAL) activity and high total phenolic content. Qualitative and quantitative estimation of phenolic compounds from tomato leaves showed significant accumulation of six phenolic acids, gallic (29.02 μg g⁻¹ fresh leaf wt), ferulic (11.44 μg g⁻¹ fresh wt), cinnamic (56.84 μg g⁻¹ fresh wt), gentisic (24.19 μg g⁻¹ fresh wt), chlorogenic acid (1.72 μg g⁻¹ fresh wt) and salicylic (0.39 μg g⁻¹ fresh wt) acid, in actinomycetes treated plants. Biochemical profiling, when correlated with plant mortality in actinomycetes treated and untreated plants, indicated that isolates vh6 and vh8 offered 44.55% and 40.14% disease reductions, respectively compared to the control. These results established that these organisms have the potential to act as biocontrol agents.     

Five New Cytotoxic Metabolites from the Marine Fungus Neosartorya pseudofischeri

The marine fungus Neosartorya pseudofischeri was isolated from Acanthaster planci from the South China Sea. In a preliminary bioactivity screening, the crude methanol extract of the fungal mycelia showed significant inhibitory activity against the Sf9 cell line from the fall armyworm Spodoptera frugiperda. Five novel compounds, including 5-olefin phenylpyropene A (1), 13-dehydroxylpyripyropene A (4), deacetylsesquiterpene (7), 5-formyl-6-hydroxy-8-isopropyl-2- naphthoic acid (9) and 6,8-dihydroxy-3-((1E,3E)-penta-1,3-dien-1-yl)isochroman-1-one (10), together with eleven known compounds, phenylpyropene A (2) and C (3), pyripyropene A (5), 7-deacetylpyripyropene A (6), (1S,2R,4aR,5R,8R,8aR)-1,8a-dihydroxy-2-acetoxy-3,8-dimethyl-5- (prop-1-en-2-yl)-1,2,4a, 5,6,7,8,8a-octahydronaphthalene (8), isochaetominine C (11), trichodermamide A (12), indolyl-3-acetic acid methyl ester (13), 1-acetyl-β-carboline (14), 1,2,3,4-tetrahydro-6-hydroxyl-2-methyl-l,3,4-trioxopyrazino[l,2-a]-indole (15) and fumiquinazoline F (16), were obtained. The structures of these compounds were determined mainly by MS and NMR data. The absolute configuration of 9 was assigned by the single-crystal X-ray diffraction studies. Compounds 1–11 and 15 showed significant cytotoxicity against the Sf9 cells from S. frugiperda.     

Meroterpenes from Endophytic Fungus A1 of Mangrove Plant Scyphiphora hydrophyllacea

Four new meroterpenes, guignardones F–I (1–4), together with two known compounds guignardones A (5) and B (6) were isolated from the endophytic fungus A1 of the mangrove plant Scyphiphora hydrophyllacea. Their structures and relative configurations were elucidated by spectroscopic data and single-crystal X-ray crystallography. A possible biogenetic pathway of compounds 1–6 was also proposed. All compounds were evaluated for inhibitory activity against methicillin-resistant Staphylococcus aureus (MRSA) and Staphylococcus aureus.     

Alkaloids from the Mangrove-Derived Actinomycete Jishengella endophytica 161111

A new alkaloid, 2-(furan-2-yl)-6-(2S,3S,4-trihydroxybutyl)pyrazine (1), along with 12 known compounds, 2-(furan-2-yl)-5-(2S,3S,4-trihydroxybutyl)pyrazine (2), (S)-4-isobutyl-3-oxo-3,4-dihydro-1H-pyrrolo[2,1-c][1,4]oxazine-6-carbaldehyde (3), (S)-4-isopropyl-3-oxo-3,4-dihydro-1H-pyrrolo[2,1-c][1,4]oxazine-6-carbaldehyde (4), (4S)-4-(2-methylbutyl)-3-oxo-3,4-dihydro-1H-pyrrolo[2,1-c][1,4]oxazine-6-carbaldehyde (5), (S)-4-benzyl-3-oxo-3,4-dihydro-1H-pyrrolo[2,1-c][1,4]oxazine-6-carbaldehyde (6), flazin (7), perlolyrine (8), 1-hydroxy-β-carboline (9), lumichrome (10), 1H-indole-3-carboxaldehyde (11), 2-hydroxy-1-(1H-indol-3-yl)ethanone (12), and 5-(methoxymethyl)-1H-pyrrole-2-carbaldehyde (13), were isolated and identified from the fermentation broth of an endophytic actinomycetes, Jishengella endophytica 161111. The new structure 1 and the absolute configurations of 2–6 were determined by spectroscopic methods, J-based configuration analysis (JBCA) method, lactone sector rule, and electronic circular dichroism (ECD) calculations. Compounds 8–11 were active against the influenza A virus subtype H1N1 with IC₅₀ and selectivity index (SI) values of 38.3(±1.2)/25.0(±3.6)/39.7(±5.6)/45.9(±2.1) μg/mL and 3.0/16.1/3.1/11.4, respectively. The IC₅₀ and SI values of positive control, ribavirin, were 23.1(±1.7) μg/mL and 32.2, respectively. The results showed that compound 9 could be a promising new hit for anti-H1N1 drugs. The absolute configurations of 2–5, ¹³C nuclear magnetic resonance (NMR) data and the specific rotations of 3–6 were also reported here for the first time.     

Dereplication Strategies for Targeted Isolation of New Antitrypanosomal Actinosporins A and B from a Marine Sponge Associated-Actinokineospora sp. EG49

High resolution Fourier transform mass spectrometry (HRFTMS) and nuclear magnetic resonance (NMR) spectroscopy were employed as complementary metabolomic tools to dereplicate the chemical profile of the new and antitrypanosomally active sponge-associated bacterium Actinokineospora sp. EG49 extract. Principal Component (PCA), hierarchical clustering (HCA), and orthogonal partial least square-discriminant analysis (OPLS-DA) were used to evaluate the HRFTMS and NMR data of crude extracts from four different fermentation approaches. Statistical analysis identified the best culture one-strain-many-compounds (OSMAC) condition and extraction procedure, which was used for the isolation of novel bioactive metabolites. As a result, two new O-glycosylated angucyclines, named actinosporins A (1) and B (2), were isolated from the broth culture of Actinokineospora sp. strain EG49, which was cultivated from the Red Sea sponge Spheciospongia vagabunda. The structures of actinosporins A and B were determined by 1D- and 2D-NMR techniques, as well as high resolution tandem mass spectrometry. Testing for antiparasitic properties showed that actinosporin A exhibited activity against Trypanosoma brucei brucei with an IC₅₀ value of 15 µM; however no activity was detected against Leishmania major and Plasmodium falciparum, therefore suggesting its selectivity against the parasite Trypanosoma brucei brucei; the causative agent of sleeping sickness.     

Identification of Two Novel Anti-Fibrotic Benzopyran Compounds Produced by Engineered Strains Derived from Streptomyces xiamenensis M1-94P that Originated from Deep-Sea Sediments

The benzopyran compound obtained by cultivating a mangrove-derived strain, Streptomyces xiamenensis strain 318, shows multiple biological effects, including anti-fibrotic and anti-hypertrophic scar properties. To increase the diversity in the structures of the available benzopyrans, by means of biosynthesis, the strain was screened for spontaneous rifampicin resistance (Rif), and a mutated rpsL gene to confer streptomycin resistance (Str), was introduced into the S. xiamenensis strain M1-94P that originated from deep-sea sediments. Two new benzopyran derivatives, named xiamenmycin C (1) and D (2), were isolated from the crude extracts of a selected Str-Rif double mutant (M6) of M1-94P. The structures of 1 and 2 were identified by analyzing extensive spectroscopic data. Compounds 1 and 2 both inhibit the proliferation of human lung fibroblasts (WI26), and 1 exhibits better anti-fibrotic activity than xiamenmycin. Our study presents the novel bioactive compounds isolated from S. xiamenensis mutant strain M6 constructed by ribosome engineering, which could be a useful approach in the discovery of new anti-fibrotic compounds.     

Bioactive hydroperoxyl cembranoids from the Red Sea soft coral Sarcophyton glaucum

A chemical investigation of an ethyl acetate extract of the Red Sea soft coral Sarcophyton glaucum has led to the isolation of two peroxide diterpenes, 11(S) hydroperoxylsarcoph-12(20)-ene (1), and 12(S)-hydroperoxylsarcoph-10-ene (2), as well as 8-epi-sarcophinone (3). In addition to these three new compounds, two known structures were identified including: ent-sarcophine (4) and sarcophine (5). Structures were elucidated by spectroscopic analysis, with the relative configuration of 1 and 2 confirmed by X-ray diffraction. Isolated compounds were found to be inhibitors of cytochrome P₄₅₀ 1A activity as well as inducers of glutathione S-transferases (GST), quinone reductase (QR), and epoxide hydrolase (mEH) establishing chemo-preventive and tumor anti-initiating activity for these characterized metabolites.     

Eight New Peptaibols from Sponge-Associated Trichoderma atroviride

Eight new and four known peptaibols were isolated from a strain of the fungus, Trichoderma atroviride (NF16), which was cultured from an Axinellid sponge collected from the East Mediterranean coast of Israel. The structures of the pure compounds were determined using HRMS, MS/MS and one- and two-dimensional NMR measurements. The isolated compounds belong to the trichorzianines, a family of 19-residue linear hydrophobic peptides containing a high proportion of α-aminoisobutyric acid (Aib), an acetylated N-terminus and a C-terminal amino alcohol. These new peptaibols exhibited antimicrobial activity against environmental bacteria isolated from the Mediterranean coast of Israel.     

Diketopiperazine Derivatives from the Marine-Derived Actinomycete Streptomyces sp. FXJ7.328

Five new diketopiperazine derivatives, (3Z,6E)-1-N-methyl-3-benzylidene-6-(2S-methyl-3-hydroxypropylidene)piperazine-2,5-dione (1), (3Z,6E)-1-N-methyl-3-benzylidene-6-(2R-methyl-3-hydroxypropylidene)piperazine-2,5-dione (2), (3Z,6Z)-3-(4-hydroxybenzylidene)-6-isobutylidenepiperazine-2,5-dione (3), (3Z,6Z)-3-((1H-imidazol-5-yl)-methylene)-6-isobutylidenepiperazine-2,5-dione (4), and (3Z,6S)-3-benzylidene-6-(2S-but-2-yl)piperazine-2,5-dione (5), were isolated from the marine-derived actinomycete Streptomyces sp. FXJ7.328. The structures of 1–5 were determined by spectroscopic analysis, CD exciton chirality, the modified Mosher’s, Marfey’s and the C₃ Marfey’s methods. Compound 3 showed modest antivirus activity against influenza A (H1N1) virus with an IC₅₀ value of 41.5 ± 4.5 μM. In addition, compound 6 and 7 displayed potent anti-H1N1 activity with IC₅₀ value of 28.9 ± 2.2 and 6.8 ± 1.5 μM, respectively. Due to the lack of corresponding data in the literature, the ¹³C NMR data of (3Z,6S)-3-benzylidene-6-isobutylpiperazine-2,5-dione (6) were also reported here for the first time.