Citreobenzofuran D-F and Phomenone A-B: Five Novel Sesquiterpenoids from the Mangrove-Derived Fungus Penicillium sp. HDN13-494.

Five new sesquiterpenoids, citreobenzofuran D-F (1-3) and phomenone A-B (4-5), along with one known compound, xylarenone A (6), were isolated from the culture of the mangrove-derived fungus Penicillium sp. HDN13-494. Their structures were deduced from extensive spectroscopic data, high-resolution electrospray ionization mass spectrometry (HRESIMS), and electronic circular dichroism (ECD) calculations. Furthermore, the absolute structures of 1 were determined by single-crystal X-ray diffraction analysis. Citreobenzofuran E-F (2-3) are eremophilane-type sesquiterpenoids with rare benzofuran frameworks, while phomenone A (4) contains a rare thiomethyl group, which is the first report of this kind of sesquiterpene with sulfur elements in the skeleton. All the compounds were tested for their antimicrobial and antitumor activity, and phomenone B (5) showed moderate activity against Bacillus subtilis, with an MIC value of 6.25 µM.

One-step optimization strategy in the simulated moving bed process with asynchronous movement of ports: A VariCol case study.

The VariCol process is a variant of the conventional simulated moving bed (SMB) process, distinguished by the asynchronous shifting of the inlet and outlet ports of the chromatographic column train. This feature allows for a more flexible operation in column utilization and can also achieve higher separation performances. However, to take full benefit out of it, the operating parameters, such as the strategy for port switching, must be optimal. in this paper, a novel methodology for optimizing those parameters, based on a single NLP (non-linear programming), is proposed. The main advantage of this approach is that it significantly reduces the complexity of the original MINLP (mixed-integer non-linear programming) formulation currently discussed in the literature. The proposed optimization problem is built, considering that the average column configuration of three zones provides the necessary and sufficient information to describe the VariCol process. Several optimization scenarios for the enantioseparation of 1,1´-bi-2-naphthol and aminoglutethimide were considered to evaluate the proposed methodology and to compare the performance of VariCol and SMB processes. The results have shown that with the single NLP approach, it is possible to explore the optimal solution in all the VariCol process domains with less computational effort than other optimization strategies reported in the literature. That is a great advantage, especially in the context of real-time applications.

Oxygenated Geosmins and Plant-like Eudesmanes from a Bacterial Mangrove Endophyte.

Geosmin (1) is a microbial terpene metabolite that is responsible for the typical smell of soil and causes an off-odor of food and water. Eudesmane sesquiterpenes are commonly found in plant essential oils. Here we describe the discovery of four geosmin-type metabolites, 7R-hydroxygeosmin (2), 3-oxogeosmin (3), 2R-hydroxy-7-oxogeosmin (4), 5-deoxy-7ß,9ß-dihydroxygeosmin (5), the plant-like eudesmanes 4ß,10α-eudesmane-5ß,11-diol (6) and (1S,5S,6S,7S,10S)-10α-eudesm-4(15)-ene-1α,6α-diol (7), and the known 1(10)E,5E-germacradiene-2,11-diol (8) from a bacterial endophyte (Streptomyces sp. JMRC:ST027706) of the mangrove plant Bruguiera gymnorrhiza. By means of NMR, MS, and ECD spectroscopy, all chemical structures as well as the absolute configurations for the new compounds were elucidated. Compounds 2-5 represent the first geosmin-related metabolites directly as bacterial natural products. The plant-derived eudesmane-5ß,11-diol (6) and (1S,5S,6S,7S,10S)-10α-eudesm-4(15)-ene-1α,6α-diol (7) are also now reported as bacterial products. The broad antimicrobial activities of 6 against a suite of fungal and bacterial pathogens including methicillin-resistant Staphylococcus aureus suggest that this terpene could be an important active principle of the medicinal plant Cymbopogon distans. The discovery of geosmin metabolites from one actinomycete indicated that these bacteria could possess enzymes for modifying geosmin and offer a possibility for bioremediation.

A novel cyanobacterial geosmin producer, revising GeoA distribution and dispersion patterns in Bacteria.

Cyanobacteria are ubiquitous organisms with a relevant contribution to primary production in all range of habitats. Cyanobacteria are well known for their part in worldwide occurrence of aquatic blooms while producing a myriad of natural compounds, some with toxic potential, but others of high economical impact, as geosmin. We performed an environmental survey of cyanobacterial soil colonies to identify interesting metabolic pathways and adaptation strategies used by these microorganisms and isolated, sequenced and assembled the genome of a cyanobacterium that displayed a distinctive earthy/musty smell, typical of geosmin, confirmed by GC-MS analysis of the culture's volatile extract. Morphological studies pointed to a new Oscillatoriales soil ecotype confirmed by phylogenetic analysis, which we named Microcoleus asticus sp. nov. Our studies of geosmin gene presence in Bacteria, revealed a scattered distribution among Cyanobacteria, Actinobacteria, Delta and Gammaproteobacteria, covering different niches. Careful analysis of the bacterial geosmin gene and gene tree suggests an ancient bacterial origin of the gene, that was probably successively lost in different time frames. The high sequence similarities in the cyanobacterial geosmin gene amidst freshwater and soil strains, reinforce the idea of an evolutionary history of geosmin, that is intimately connected to niche adaptation.

Naphthalenones and Naphthols Isolated from the Saussurea laniceps Endophytic Fungus Didymella glomerata X223.

One new naphthalenone, didymelol A, and three new naphthols, didymelol B-D, together with three known naphthalenones, (3S,4R)-3,4,6-trihydroxy-3,4-dihydronaphthalen-1(2H)-one, (4S)-4,6-dihydroxy-3,4-dihydronaphthalen-1(2H)-one, (4S)-4-hydroxy-3,4-dihydronaphthalen-1(2H)-one, were isolated from the Saussurea laniceps endophytic fungus Didymella glomerata X223. The structures of the isolates were elucidated based on extensive spectroscopic data analysis. The absolute configuration of didymelol A was established through single-crystal X-ray diffraction data and didymelols B-D were identified through comparisons of experimental and calculated ECD spectra. All compounds were evaluated for cytotoxic activity against human non-small cell lung cancer A549 cells and human breast carcinoma MDA-MB-435 cells.

Ultrasound-assisted hydrophobic deep eutectic solvent based solid-liquid microextraction of Sudan dyes in spice samples.

An environmentally friendly, simple method was carried out with the help of an ultrasonic assisted solid-liquid microextraction technique using a new deep eutectic solvent (DES) for the extraction and determination of Sudan dyes (I-IV) in spice samples. In this method, parameters affecting the optimization were researched and optimized such as DES composition, DES volume, ultrasonic time, temperature and, centrifuge time. The analytical performance of the developed method was quite satisfactory, the R2 values were higher than 0.9989, and the limits of quantification were <1.17 µg g-1. Two different concentrations (10-50 µg g-1) were spiked to Chili peppers, paprika, cumin and sumac spices for the applicability and accuracy of the developed microextraction method. Some of these spices were found to contain Sudan I and IV dyes. The recovery values for spiked samples were found to be between 85.55% and 99.29% and relative standard deviations were found to be <3.17% when using a 10 µg g-1 Sudan dyes concentration. The results showed that the developed method can be successfully applied for extraction and determination of Sudan dyes in spice samples.

Overturning the Peribysin Family Natural Products Isolated from Periconia byssoides OUPS-N133: Synthesis and Stereochemical Revision of Peribysins A, B, C, F, and G.

Herein we report the stereochemical revision of peribysins A, B, C, F, and G, guided by enantiospecific total synthesis starting from (+)-nootkatone. Furthermore, we reconfirmed the absolute stereochemistry of peribysin Q. The highlights of the synthesis are enone transposition and kinetic iodination resulting in separation of diastereomers. Our findings coupled with synthetic and biological data previously reported by Danishefsky's group suggest that the original stereochemistries of peribysins A, B, C, F, and G were misassigned.

Potentiometric E-Tongue System for Geosmin/Isoborneol Presence Monitoring in Drinkable Water.

A potentiometric E-tongue system based on low-selective polymeric membrane and chalcogenide-glass electrodes is employed to monitor the taste-and-odor-causing pollutants, geosmin (GE) and 2-methyl-isoborneol (MIB), in drinkable water. The developed approach may permit a low-cost monitoring of these compounds in concentrations near the odor threshold concentrations (OTCs) of 20 ng/L. The experiments demonstrate the success of the E-tongue in combination with partial least squares (PLS) regression technique for the GE/MIB concentration prediction, showing also the possibility to discriminate tap water samples containing these compounds at two concentration levels: the same OTC order from 20 to 100 ng/L and at higher concentrations from 0.25 to 10 mg/L by means of PLS-discriminant analysis (DA) method. Based on the results, developed multisensory system can be considered a promising easy-to-handle tool for express evaluation of GE/MIB species and to provide a timely detection of alarm situations in case of extreme pollution before the drinkable water is delivered to end users.

Chemically modified chitosan­sodium alginate as chemo-sensor adsorbent for the detection of picric acid and removal of biebrich scarlet.

We report here on the green synthesis method of hydrogel nanocomposite (Na-Ala/Chit-cl-polyAAm/CQDs) incorporated with carbon quantum dots for picric acid sensing and biebrich scharlet dye removal from industrial waste water. The nanocomposite precursor was derived from chitosan­sodium alginate hybrid backbone and acrylamide monomer through the formation of semi-IPN matrix (Na-Ala/Chit-cl-polyAAm). The swelling percentage of semi-IPN can be controlled through process parameters such as reaction time, temperature, pH, water volume, acrylamide, N,N'-methylenebisacrylamide and ammonium persulphate concentrations. Hydrogel nanocomposite displayed 99% quenching efficiency for the selective detection of picric acid and 96% dye removal efficiency was found to be observed for the removal of biebrich scarlet dye. The sorption was found to be favorable though Freundlich and Temkin adsorption isotherms along with the 2nd order kinetics. The devices were found to be recyclable and reusable up to six consecutive cycles indicating their applicability in textile industries for the treatment of effluents.

Development of a liquid chromatography atmospheric pressure chemical ionization mass spectrometry method for determining off-flavor compounds and its application toward marine recirculating aquaculture system monitoring and evaluation of aeration as a depuration approach.

The off-flavor compounds geosmin and 2-methylisoborneol (2-MIB) are well-known to impact the quality of farmed freshwater fish species, but little is known about off-flavors in marine aquaculture. To begin addressing this knowledge gap, a method for determining geosmin and 2-MIB using LC with atmospheric pressure chemical ionization (APCI) MS detection was developed. While 2-MIB was readily detected using LC-APCI/MS, geosmin exhibited on-column degradation that was independent of column chemistry and could not be eliminated. Optimized conditions were identified that balanced the separation and ionization efficiency of 2-MIB and geosmin while minimizing geosmin degradation, but the overall method sensitivity for geosmin was reduced by the on-column losses. The method was used with direct aqueous injections to determine the volatilization rates of geosmin and 2-MIB at ppb levels during aeration under laboratory conditions in both salt water and pure water to simulate marine and fresh water aquaculture, respectively. The volatilization rates of both compounds were 30% faster in salt water than in fresh water with or without aeration, but aeration was found to enhance the rate by a factor of 2.5 in both water types. The LC-APCI/MS method was combined with stir bar sorptive extraction (SBSE) to achieve greater sensitivity for determining off-flavors in recirculating aquaculture system (RAS) water. Using SBSE-LC-APCI/MS, the LODs for geosmin and 2-MIB were 70 ng/kg (part per trillion) and 6 ng/kg, respectively. The on-column losses resulted in a relatively high LOD for geosmin that renders this method unsuitable for determining geosmin at the low ng/kg levels expected in RAS. SBSE using both grab water samples and an in-situ diving unit were used to evaluate 2-MIB levels in the culture water of two separate marine RAS that were supporting the growth of European sea bass but had differing levels of water treatment. 2-MIB was readily detected using both SBSE approaches in the RAS with less sophisticated treatment when the animal stocking density was at its highest (50 kg/m3) but was not detected in the more sophisticated RAS regardless of stocking density. Geosmin was not detected in either system, but the results were inconclusive given its higher LOD. These limited results suggest that the anaerobic water treatment components, present only in the more sophisticated RAS, maintained the level of 2-MIB below the LOD.

Protective effect of hypoxylonol C and 4,5,4',5'-tetrahydroxy-1,1'-binaphthyl isolated from Annulohypoxylon annulatum against streptozotocin-induced damage in INS-1 cells.

We evaluated the protective effects of hypoxylonol C and 4,5,4',5'-tetrahydroxy-1,1'-binaphthyl (BNT) isolated from Annulohypoxylon annulatum on pancreatic ß-cell apoptosis, using the ß-cell toxin streptozotocin (STZ). Hypoxylonol C and BNT restored the STZ-induced decrease in INS-1 cell viability in a dose-dependent manner. In addition, treatment of INS-1 cells with 50 µM STZ resulted in an increase in apoptotic cell death, which was observed as annexin V fluorescence intensity. Apoptotic cell death was decreased by co-treatment with 100 µM hypoxylonol C and 100 µM BNT. Similarly, STZ caused a marked increase in the expression of cleaved caspase-8, caspase-3, Bax, and poly (ADP-ribose) polymerase (PARP), as well as a decrease in the expression of B-cell lymphoma 2 (Bcl-2), which was reversed by co-treatment with 100 µM hypoxylonol C and 100 µM BNT. These findings suggest that hypoxylonol C and BNT play an important role in protecting pancreatic ß-cells against apoptotic damage.

Analysis of Pesticide Residue in Tomatoes by Carbon Nanotubes/ß-Cyclodextrin Nanocomposite Reinforced Hollow Fiber Coupled with HPLC.

For addressing the issues of pesticide residue analysis characterized by the trace levels of target analytes and the complexity of sample matrices, a selective extracting material, carbon nanotubes (CNTs)/ß-cyclodextrin (ß-CD) nanocomposite reinforced hollow fiber (HF), was developed. CNTs were chemically modified with ß-CD and then the resultant nanocomposite was immobilized into the wall pores and lumen of HF by sol-gel technology. The reinforced HF was applied to direct-immersion mode of solid phase microextraction for the determination of carbaryl and 1-naphthol in tomatoes, coupled with high performance liquid chromatography. The proposed method provided 240- and 215-fold enrichment factors, good linearity in the range of 0.6 to 600 ng/g and 0.2 to 600 ng/g, good repeatability with RSDs of 4.5% and 6.9%, and batch-to-batch reproducibility with RSDs of 7.4% and 8.3% for 1-naphthol and carbaryl, respectively. Moreover, the low limits of detection at 0.05 and 0.15 ng/g for 1-naphthol and carbaryl, respectively, along with the high recovery in the range of 84.2% to 108.9% were obtained. The results showed that the material combined the respective advantages of CNTs, ß-CD, and HF, thus, exhibiting efficient adsorption property, outstanding molecular recognition performance, and excellent sample clean-up effect, and it is applicable for pesticide residue analysis in complex matrices. PRACTICAL APPLICATION: The developed extracting material can be used for pesticide residue analysis of tomatoes. Pesticides, carbaryl, and 1-naphthol were detected in tomatoes, the most popular vegetable grown and consumed globally. The results supported the necessity to monitor pesticide residue for public health.

Aromatic compounds produced by endophytic fungi isolated from red alga Asparagopsis taxiformis - Falkenbergia stage.

Endophytic fungi were isolated from red alga Asparagopsis taxiformis - Falkenbergia stage, collected from the Brazilian coast, and were identified as Annulohypoxylon stygium (AT-03) and A. yungensis (AT-06) based on their macro/micromorphological and molecular features. Bioassay-guided fractionation of the EtOAc extract from laboratory cultures of both strains yielded known compounds pyrogallol from A. stygium, (3 R)-scytalone and (3 R,4 R)-4-hydroxy-scytalone from A. yungensis. Pyrogallol was active against methicillin-resistant Staphylococcus aureus (MRSA) and Escherichia coli strains. An inactive fraction from A. stygium afforded two additional compounds, (3 R,4 R)-3,4,5-trihydroxy-1-tetralone and tyrosol. Optically active compounds had their stereochemistry determined by circular dichroism (CD) spectroscopy.

[Removing Typical Odorants in Drinking Water by Vacuum Ultraviolet Combined with Chlorine].

For the effective removal of two typical odorants found in drinking water, 2-methylisoborneol (2-MIB) and geosmin (GSM), which cannot be effectively removed by the conventional water treatment processes, the advanced oxidation process of vacuum ultraviolet combined with chlorine (VUV/chlorine) was studied. The efficiency of this technology in the removal of these typical odorants was investigated; the effects of ultraviolet intensity, chlorine concentration, pH, bicarbonate concentration, and humic acid concentration on the degradation of these typical odorants were examined, and the role of hydroxyl radicals (·OH) in the degradation of these typical odorants was analyzed. The purge and trap method coupled with gas chromatography and mass spectrometry (GC/MS) was used to determine the concentrations of the typical odorants. The results showed that the VUV/chlorine technology removed typical odorants effectively, and the removal rates of 2-MIB and GSM increased by 15% and 8%, respectively, in 30 minutes, compared with that by the UV/chlorine technology. With the increase in chlorine concentration and ultraviolet intensity, the degradation rates of the typical odorants was accelerated. The removal of the typical odorants was obvious under weak acid condition, and the removal rates of 2-MIB and GSM reached 95% and 96%, respectively, in 10 minutes under the condition of pH 5. Bicarbonate and humic acid competed with free radicals in the reaction system to inhibit the degradation of the typical odorants. The removal rates of 2-MIB and GSM decreased appreciably by 40% and 31%, respectively, when 1 mmol·L-1tert-butanol was added to the reaction mixture, which indicated that hydroxyl radicals (·OH) played a major role in the removal of these typical odorants.

Mono- and Dimeric Naphthalenones from the Marine-Derived Fungus Leptosphaerulina chartarum 3608.

Five new naphthalenones, two enantiomers (−)-1 and (+)-1 leptothalenone A, (−)-4,8-dihydroxy-7-(2-hydroxy-ethyl)-6-methoxy-3,4-dihydro-2H-naphthalen-1-one ((−)-2), (4S, 10R, 4’S)-leptotha-lenone B (5), (4R, 10S, 4’S)-leptothalenone B (6), and a new isocoumarine, 6-hydroxy-5,8-dimethoxy-3-methyl-1H-isochromen-1-one (4), along with two known compounds (+)-4,8-dihydroxy-7-(2-hydroxy-ethyl)-6-methoxy-3,4-dihydro-2H-naphthalen-1-one ((+)-2) and (+)-10-norparvulenone (3) were isolated from the marine-derived fungus Leptosphaerulina chartarum 3608. The structures of new compounds were elucidated by HR-ESIMS, NMR, and ECD analysis. All compounds were evaluated for cytotoxicity and anti-inflammatory activity. Compound 6 showed moderate anti-inflammatory activity by inhibiting the production of nitric oxide (NO) in lipopolysaccharide-stimulated RAW264.7 cells, with an IC50 value of 44.5 μM.

γ-Fe2O3 magnetic nanoparticle functionalized with carboxylated multi walled carbon nanotube for magnetic solid phase extractions and determinations of Sudan dyes and Para Red in food samples.

Hybrid nanostructures composed of γ-Fe2O3 (maghemite) and carboxylated-multi walled carbon nanotube (cMWCNT) were used for the magnetic solid phase extractions and determination of Sudan I, II, III, IV, Para Red, Sudan Black B and Sudan Red 7B in chili products. High performance liquid chromatography (HPLC) was employed for the measurements. Limit of quantification (LOQ) values were found in the range 0.44-2.82ngmL-1 for analytes. The best extraction parameters were determined as pH 8.0, 40mg of magnetic nanoparticle, 4.0min of contact time, 0.3mL desorption by acetonitrile. The samples were dissolved in acetone-dichloromethane-methanol (3:2:1, v/v/v) and diluted with acetonitrile-methanol (v/v; 80:20) before the method was applied. Concentrations of Sudan dyes and Para Red were determined in four samples of chili powder from less than LOQ to 31.21±1.6ngg-1, two samples of chili tomato sauces (lower than LOQ) and two samples of ketchup (lower than LOQ).

Synthesis and evaluation of pseudopeptide chiral stationary phases for enantioselective resolution.

Poly(2-oxazoline)s are regarded as bioinspired polymers due to their structural relation to polypeptides. In this work, a new kind of poly(2-oxazoline)s containing dipeptide segments in the side chains was synthesized through a bottom-up protocol, which involves ring-opening copolymerization of 2-(N-Boc-l-2-pyrrolidinyl)-2-oxazoline (PyOXBoc) with 2-(3-butenyl)-2-oxazoline (BuOX) followed by deprotection and amide coupling with N-protected L-proline. The resulting vinyl-functionalized polymers were subsequently immobilized onto mercaptopropylated silica bead matrices by means of thio-click chemistry and their potential as the chiral stationary phase (CSP) for high-performance liquid chromatography was preliminarily evaluated with a series of structurally different racemates. The results showed that this class of pseudopeptide CSPs is particularly adapted to the enantiomeric separation of 1,1'-bi-2-naphthol and acyloin compounds (such as benzoin) under normal-phase conditions. Moreover, an increase in the length of polymer main chains is beneficial to the enhancement of both enantioselectivity and resolution ability. The chiral discrimination of analytes by the polymeric selectors stems primarily from hydrogen bonding and π-π interactions as well as steric hindrance.

Hepatoprotective naphthalene diglucoside from Neanotis wightiana aerial parts.

BACKGROUND: Neanotis wightiana (Wall. ex Wight & Arn) W.H. Lewis has been used in traditional medicine in India for the treatment of liver disorders. In fact, this plant is frequently used by the local people of Tripura for the treatment of liver disorder problems. In previous study on this plant we have isolated a hepatoprotective saponin, neanoside A. PURPOSE: Evaluation of in vivo hepatoprotective effects of isolated compounds from N. wightiana aerial parts on serum hepatic-biomarkers in CCl4- induced hepatotoxicity in rats to validate the traditional use of the plant. STUDY DESIGN: This study was designed to isolate more hepatoprotective compounds from N. wightiana aerial parts and evaluate their in vivo hepatoprotective activity in animal model. METHODS: The phytochemicals from the polar n-butanol fraction of methanolic extract of N. wightiana aerial parts were isolated by repeated column chromatography over Diaion HP-20 and silica gel. Among the isolated three compounds, two were known triterpenoids, ursolic acid and oleanolic acid. The new compound was named neanoside B and its structure was established as naphthalene diglucoside 1 on the basis of extensive spectroscopic (including 2D NMR) analysis. Furthermore, the hepatoprotective activity of 1 was evaluated on CCl4 -induced hepatic injured rats by oral administration at three doses (5, 10 mg and 20 mg/kg) for 7 d and the assay of serum hepatic injury marker enzymes, SGPT, SGOT, ALP and bilirubin contents and histopathological changes of injured liver tissue after 7 d The herbal hepatoprotective drug, silymarin (100 mg/kg) was as positive control. RESULTS: The structure of the new compound, neanoside B (1) was elucidated as 1,4-dihydroxy-2-(methoxymethyl)naphthalen-3-yl-methyl-3-ß-d-glucopyranosyl-(1→6)-ß-d-glucopyranoside on the basis of extensive spectroscopic (including 2D-NMR) and chemical studies. The compound 1 exhibited significant in vivo hepatoprotective effect at the tested doses of 5, 10 and 20 mg/kg bw in CCl4-induced hepatotoxicity in rats. In a dose-dependent manner, 1 normalized the elevated levels of hepatic injury marker enzymes, serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), alkaline phosphatase (ALP) and total bilirubin and ameliorated the damage of liver tissue by reducing the necrosis and vacuoles. Possibly compound 1 ameliorated the hepatic damage in hepatotoxic rats by improving the antioxidant status. The higher dose (20 mg/kg) showed more hepatoprotective effect by reducing the elevated levels of SGPT, SGOT, ALP and bilirubin content to 388.5 ± 2.156, 160.7 ± 3.00, 198.6 ± 4.562 and 0.652 ± 0.036 IU/ml, respectively, compared to the levels in the control group (583.2 ± 6.922, 324.6 ± 4.711, 263.9 ± 4.939 and 1.533 ± 0.042 IU/ml, respectively) and the effect was comparable to that of the positive control silymarin (100 mg/kg bw) (389.4 ± 6.348, 167.9 ± 4.289, 203.3 ± 4.448 and 0.816 ± 0.030 IU/ml, respectively). CONCLUSIONS: This study indicated that isolated neanoside B (1) from Neanotis wightiana could be a potential drug in liver disorders. Further study in pharmacokinetics and long-term toxicity of compound 1 is requested for its clinical setting as effective drug in liver disorders.

Larrea tridentata: A novel source for anti-parasitic agents active against Entamoeba histolytica, Giardia lamblia and Naegleria fowleri.

Protozoan parasites infect and kill millions of people worldwide every year, particularly in developing countries where access to clean fresh water is limited. Among the most common are intestinal parasites, including Giardia lamblia and Entamoeba histolytica. These parasites wreak havoc on the epithelium lining the small intestines (G. lamblia) and colon (E. histolytica) causing giardiasis and amebiasis, respectively. In addition, there are less common but far more deadly pathogens such as Naegleria fowleri that thrive in warm waters and infect the central nervous systems of their victims via the nasal passages. Despite their prevalence and associated high mortality rates, there remains an unmet need to identify more effective therapeutics for people infected with these opportunistic parasites. To address this unmet need, we have surveyed plants and traditional herbal medicines known throughout the world to identify novel antiparasitic agents with activity against G. lamblia, E. histolytica, and N. fowleri. Herein, we report Larrea tridentata, known as creosote bush, as a novel source for secondary metabolites that display antiparasitic activity against all three pathogens. This report also characterizes the lignan compound classes, nordihydroguairetic acid and demethoxyisoguaiacin, as novel antiparasitic lead agents to further develop more effective drug therapy options for millions of people worldwide.

Five Unprecedented Secondary Metabolites from the Spider Parasitic Fungus Akanthomyces novoguineensis.

Five new compounds including the glycosylated ß-naphthol (1, akanthol), a glycosylated pyrazine (2, akanthozine), and three amide derivatives including a hydroxamic acid derivative (3-5) were isolated from the spider-associated fungus Akanthomyces novoguineensis (Cordycipitaceae, Ascomycota). Their structures were elucidated by using high resolution mass spectrometry (HRMS) and NMR spectroscopy. In this study, the antimicrobial, cytotoxic, anti-biofilm, and nematicidal activities of the new compounds were evaluated. The distribution pattern of secondary metabolites in the species was also revealed in which more isolates of A. novoguineensis were encountered and their secondary metabolite profiles were examined using analytical HPLC with diode array and mass spectrometric detection (HPLC-DAD/MS). Remarkably, all isolated compounds are specifically produced by A. novoguineensis.