A novel magnetic solid-phase extraction method for detection of 14 heterocyclic aromatic amines by UPLC-MS/MS in meat products.

The current study developed a cheap and effective method for the simultaneous extraction of 14 heterocyclic aromatic amines (HAAs) in food matrix. Core-shell Fe3O4@PDA nanoparticles were constructed and acted as the magnetic solid-phase extraction adsorbent to separate and purify HAAs from meat products for the first time. Then, UPLC-MS/MS technique was employed to identify and quantify the HAAs easily. Fe3O4@PDA nanoparticles were synthesized and characterized successfully. Totally 14 HAAs were completely separated in 19.99 min with good regression coefficients. LODs and LOQs were in the range of 0.013-0.247 ng/g and 0.056-0.803 ng/g, respectively. The intra-day precisions and inter-day precisions were below 9%. Except for IQ[4,5-b], Phe-p-1, PhIP, other 11 types of HAAs (DMIP, 1,5,6-TMIP, IQ, IQx, MeIQ, MeIQx, 7,8-DiMeIQx, AαC, MeAαC, Harman, Norharman) could acquire relatively high recoveries (71.06%-108.49%). The proposed method was successfully devoted to the evaluation of HAAs levels in 8 commercial meat products to verify the adaptability.

Development of a Solid-Phase Microextraction-Gas Chromatography/Mass Spectrometry Method for Quantifying Nitrogen-Heterocyclic Volatile Aroma Compounds: Application to Spirit and Wood Matrices.

Over wood aging, matured spirits developed a complex aromatic bouquet where roasted-like notes were often perceived. Since many nitrogen heterocycles were related to these olfactory nuances, a headspace solid-phase microextraction (HS-SPME) coupled to gas chromatography-mass spectrometry was developed and validated to quantify them in both spirit and wood matrices. The various parameters affecting the extraction of the analytes from both spirit and wood samples were first investigated (i.e., fiber coating phase, dilution, pH and volume sample, adding salt, extraction time and temperature, and incubation time) to determine the best compromise for a single-run analysis of the whole set of studied compounds. Good linearity (R2 > 0.99), repeatability, reproducibility, accuracy and low detection, and quantification limits were obtained, making this analytical method a suitable tool for routine analysis of the selected nitrogen compounds. Fifteen pyrazines, three pyrroles, and three quinolines were quantified in a series of oak wood and commercial spirit samples where some of them were identified for the first time. The significant impact of some barrel features and the spirit in-wood maturation step on the N-heterocycle profile in both matrices were finally discussed.

Sorbicillfurans A and B, two novel sorbicillinoid adducts from the fungus Penicillium citrinum SCSIO41402.

Two novel sorbicillinoid adducts containing bicyclo[2.2.2]octane and tetrahydrofuran moieties, named sorbicillfurans A and B (1 and 2), were isolated from the static culture of the marine-derived fungus Penicillium citrinum SCSIO41402. Their structures including absolute configurations were determined by spectroscopic and calculated ECD analyses. Sorbicillfurans A and B (1 and 2) are the first examples of sorbicillinoids possessing a tetrahydrofuran unit. In the proposed biosynthetic pathway, sorbicillfuran B (2), harboring a rare and complex polycyclic framework, is probably formed by two Diels-Alder reactions. Both isolates were evaluated for the cytotoxicity against six human cancer cell lines, only sorbicillfuran B (2) showed weak cytotoxicity against HL-60 cells with an IC50 value of 9.6 µM.

Recognition of Pharmacological Bi-Heterocyclic Compounds by Using Terahertz Time Domain Spectroscopy and Chemometrics.

In this study, we presented the concept and implementation of a fully functional system for the recognition of bi-heterocyclic compounds. We have conducted research into the application of machine learning methods to correctly recognize compounds based on THz spectra, and we have described the process of selecting optimal parameters for the kernel support vector machine (KSVM) with an additional `unknown' class. The chemical compounds used in the study contain a target molecule, used in pharmacy to combat inflammatory states formed in living organisms. Ready-made medical products with similar properties are commonly referred to as non-steroidal anti-inflammatory drugs (NSAIDs) once authorised on the pharmaceutical market. It was crucial to clearly determine whether the tested sample is a chemical compound known to researchers or is a completely new structure which should be additionally tested using other spectrometric methods. Our approach allows us to achieve 100% accuracy of the classification of the tested chemical compounds in the time of several milliseconds counted for 30 samples of the test set. It fits perfectly into the concept of rapid recognition of bi-heterocyclic compounds without the need to analyse the percentage composition of compound components, assuming that the sample is classified in a known group. The method allows us to minimize testing costs and significant reduction of the time of analysis.

Cytotoxic Sesquiterpenoid Quinones and Quinols, and an 11-Membered Heterocycle, Kauamide, from the Hawaiian Marine Sponge Dactylospongia elegans.

Several known sesquiterpenoid quinones and quinols (1-9), and kauamide (10), a new polyketide-peptide containing an 11-membered heterocycle, were isolated from the extracts of the Hawaiian marine sponge Dactylospongia elegans. The planar structure of 10 was determined from spectroscopic analyses, and its relative and absolute configurations were established from density functional theory (DFT) calculations of the GIAO NMR shielding tensors, and advanced Marfey's analysis of the N-MeLeu residue, respectively. Compounds 1 and 3 showed moderate inhibition of ß-secretase 1 (BACE1), whereas 1-9 exhibited moderate to potent inhibition of growth of human glioma (U251) cells. Compounds 1-2 and 4-7 were also active against human pancreatic carcinoma (Panc-1) cells.

Emergence of mutagenic/carcinogenic heterocyclic amines in traditional Saudi chicken dishes prepared from local restaurants.

In the current investigation, five most potential HAs (MeIQx, 4,8-DiMeIQx, IQ, MeIQ and PhIP) were analyzed in traditional Saudi chicken dishes (shawaya, Ala Al-Faham, kebab, saleeg, mandi, kabsa and madhbi) prepared from local restaurants. The aims of the present study were to identify the presence of HAs in cooked chicken dishes, and to conclude how the levels and types of HAs could be affected by cooking methods and food ingredients. In control samples, HAs were found at higher levels ranged from not quantified to 33.72 ng/g. Nonetheless, in chicken dishes, the HAs (MeIQx, 4,8-DiMeIQx and PhIP) amounts are varied at higher range and relatively detected at lower levels from not quantified to 16.35 ng/g, IQ and MeIQ were not identified in any of the studied chicken dishes except shawaya where found to be not quantified. The HAs reduction rates were obtained at higher values in all of the studied samples, among them mandi sample demonstrates the reduction rates higher than 70%, whereas saleeg sample shows the reduction rates almost 100% except PhIP (~95%). The obtained outcomes have markedly showed that HAs occurrence in thermally processed chicken dishes is extremely affected from both cooking methods and addition of food ingredients.

Detoxification of Heterocyclic Aromatic Amines by Probiotic to Inhibit Medical Hazards.

Cancer is the second leading factor of human death in the world. Long-term consumption of cooked red meat brings about various types of cancers like colorectal cancer due to the formation of Heterocyclic Aromatic Amines (HAAs) during the heating process of meat. There are various solutions for the reduction of these toxicants. The aim of this article is to describe probiotic as one of the possible strategies for bioremoval of these carcinogenic and mutagenic substances and change food to functional one as well. The mechanism of biodetoxification is binding by probiotics, which depends on some variables including the probiotic characteristics, kind and content of the mutagens, as well as some properties of media. In this article, after introducing detoxification ability of probiotics and listing of all reported probiotics in this field, the influencing variables are surveyed and finally, opportunities and problems of HAA bioremoval by probiotics are described.

(+)- and (-)-Preuisolactone A: A Pair of Caged Norsesquiterpenoidal Enantiomers with a Tricyclo[4.4.01,6.02,8]decane Carbon Skeleton from the Endophytic Fungus Preussia isomera.

A pair of enantiomeric norsesquiterpenoids, (+)- and (-)-preuisolactone A (1) [(+)-1 and (-)-1)] featuring an unprecedented tricyclo[4.4.01,6.02,8]decane carbon scaffold were isolated from Preussia isomera. Their structures were determined by spectroscopic and computed methods and X-ray crystallography. Compounds (+)-1 and (-)-1 are two rare naturally occurring sesquiterpenoidal enantiomers. A plausible biosynthetic pathway for 1 is proposed. Additionally, (±)-1 exhibited remarkable antibacterial activity against Micrococcus luteus with an MIC value of 10.2 µM.

Facile synthesis of magnetic zinc metal-organic framework for extraction of nitrogen-containing heterocyclic fungicides from lettuce vegetable samples.

We present a simple method for the fabrication of a magnetic amino-functionalized zinc metal-organic framework based on a magnetic graphene oxide composite. The resultant framework exhibited a porous 3D structure, high surface area and good adsorption properties for nitrogen-containing heterocyclic fungicides. The adsorption process and capacity indicated that the primary adsorption mechanism might be hydrogen bonding and π-π conjugation. In addition, an optimized protocol for magnetic solid phase extraction was developed (such as adsorbent content, pH, and desorption solvent), and utilized for the extraction of nitrogen-containing heterocyclic fungicides from vegetable samples. Quantitation by high performance liquid chromatography coupled with tandem mass spectrometry offered a detection limit of 0.21-1.0 µg/L (S/N = 3) with correlation coefficients larger than 0.9975. These results demonstrate that magnetic amino-functionalized zinc metal-organic framewor is a promising adsorbent for the extraction and quantitation of nitrogen-containing heterocyclic fungicides.

Heterocyclic cellular lipid peroxidation inhibitors inspired by the marine antioxidant barettin.

The marine environment remains a rich source for the discovery and development of novel bioactive compounds. The present paper describes the design, synthesis and biological evaluation of a library of small molecule heterocyclic mimetics of the marine 2,5-diketopiperazine barettin which is a powerful natural antioxidant. By mainly focusing on the influence from the brominated indole and heterocyclic core of barettin, a library of 19 compounds was prepared. The compounds comprised a heterocyclic core, either a 2,5 diketopiperazine, an imidazolidinedione or a thioxothiazolidinone, which were mainly monosubstituted with ranging bulky substituents. The prepared compounds were screened for activity in a cellular lipid peroxidation assay using HepG2 cells. Several of the synthetic compounds showed antioxidant properties superior to the positive control barettin. Two of the prepared compounds displayed inhibitory activity similar to commercial antioxidants with significant inhibition at low µg/mL concentrations. The toxicity of the compounds was also investigated against MRC-5 lung fibroblasts and none of the included compounds displayed any toxicity at 50 µg/mL.

Acetonitrile extraction coupled with UHPLC-MS/MS for the accurate quantification of 17 heterocyclic aromatic amines in meat products.

This study proposed a simple and accurate acetonitrile extraction pretreatment method coupled with ultrahigh-performance liquid chromatography with tandem mass spectrometry for the simultaneous determination of 17 heterocyclic aromatic amines (HAAs) in meat products. With this new method, all 17 HAAs, including 11 polar and 6 nonpolarHAAs, were simultaneously extracted by acetonitrile and purified by one-step Oasis MCX cartridge purification. Compared with two different improved reference methods, the acetonitrile method could obtain higher recoveries (in the range of 42.5% to 99.0%) and better repeatability (lower than 12.2%). The limits of quantification were calculated between 0.028ngg-1and0.648ngg-1 with high correlation coefficients (r>0.9976) in wide linear ranges. The proposed acetonitrile method was successfully applied to the analysis of the HAAs levels in 10 commercial meat products with satisfactory recoveries.

New heterocyclic compounds from Ranunculus ternatus Thunb.

Five new heterocyclic compounds, 5-α-d-fructofuranosylmethyl-furfural (1), 5-ß-d-fructofuranosylmethyl-furfural (2), 5-ß-d-fructopyranosylmethyl-furfural (3), 4-(2-((2S-2,3-dihydroxypropoxy)methyl)-5-formyl-1H-pyrrol-1-yl)butanoic acid (4), and 3S,4S-4,5,8-trihydroxy-3-(prop-1-en-2-yl)isochroman-1-one (5), were obtained from the root of Ranunculus ternatus Thunb., which is a traditional Chinese anti-tuberculosis medicine. Their structures were elucidated by UV, IR, HRESIMS, NMR data, and the comparison of experimental and calculated electronic circular dichroism (ECD) spectra. Notably, compounds 1-3 are rarely occurring furfural fructosides in natural sources. These heterocyclic compounds could be further studied for the synthetic chemists and pharmacologists due to the source and structural properties.

Subcritical Water Chromatography with Electrochemical Detection.

Reverse phase liquid chromatography (RPLC) is a commonly used separation and analysis technique. RPLC typically employs mixtures of organic solvents and water or aqueous buffers as the mobile phase. With RPLC being used on a global scale, enormous quantities of organic solvents are consumed every day. In addition to the purchasing cost of the hazardous solvents, the issue of waste disposal is another concern. At ambient temperature, water is too polar to dissolve many organic substances. Therefore, although water is nontoxic it cannot be used to replace the mobile phase in RPLC since organic analytes will not be eluted. Subcritical water chromatography may be an alternative. The characteristics of water, such as polarity, surface tension, and viscosity, can be altered by manipulating water's temperature, thus making it behave like an organic solvent. The aim of this study was to evaluate the feasibility of separation using water mobile phase and detection by an electrochemical (EC) detector. The classes of analytes studied were neurotransmitters/metabolites, nucleic acids/heterocyclic bases, and capsaicinoids. Both isothermal and temperature-programmed separations were carried out. The separation temperature ranged from 25 to 100 °C. For separations of all three classes of solutes, the retention time was decreased with increasing temperature, thus shortening the analysis time. The peaks also became narrower as temperature increased. The limit of detection of neurotransmitters/metabolites ranges from 0.112 to 0.224 ppm.

Development and comparison of HPLC and MEKC methods for the analysis of cyclic sulfur mustard degradation products.

In this study, novel, fast, and simple methods based on RP-HPLC and MEKC with DAD are developed and validated for the qualitative and quantitative determination of five cyclic sulfur mustard (HD) degradation products (1,4-thioxane, 1,3-dithiolane, 1,4-dithiane, 1,2,5-trithiepane, and 1,4,5-oxadithiepane) in water samples. The HPLC method employs a C18 column and an isocratic water-ACN (55:45, v/v) mobile phase. This method enables separation of all five cyclic compounds within 8 min. With the CE method, the baseline separation of five compounds was achieved in less than 11 min by applying a simple BGE composed of a 10 mM borate buffer and 90 mM SDS (pH 9.15). Both methods showed good linear correlation (R2 > 0.9904). The detection limits were in the range of 0.08-0.1 µM for the HPLC method and 10-20 µM for MEKC. The precision tests resulted in RSDs for migration times and peak areas less than 0.9 and 5.5%, respectively, for the HPLC method, and less than 1.1 and 7.7% for the MEKC method, respectively. The developed methods were successfully applied to the analysis of five cyclic HD degradation products in water samples. With the HPLC method, the LODs were lowered using the SPE for sample purification and concentration.

O-heterocyclic derivatives with antibacterial properties from marine bacterium Bacillus subtilis associated with seaweed, Sargassum myriocystum.

The brown seaweed, Sargassum myriocystum associated with heterotrophic bacterium, Bacillus subtilis MTCC 10407 (JF834075) exhibited broad-spectra of potent antibacterial activities against pathogenic bacteria Aeromonas hydrophila, Vibrio vulnificus, and Vibrio parahaemolyticus. B. subtilis MTCC 10407 was found to be positive for polyketide synthetase (pks) gene, and therefore, was considered to characterize secondary metabolites bearing polyketide backbone. Using bioassay-guided fractionation, two new antibacterial O-heterocyclic compounds belonging to pyranyl benzoate analogs of polyketide origin, with activity against pathogenic bacteria, have been isolated from the ethyl acetate extract of B. subtilis MTCC 10407. In the present study, the secondary metabolites of B. subtilis MTCC 10407 with potent antibacterial action against bacterial pathogens was recognized to represent the platform of pks-1 gene-encoded products. Two homologous compounds 3 (3-(methoxycarbonyl)-4-(5-(2-ethylbutyl)-5,6-dihydro-3-methyl-2H-pyran-2-yl)-butyl benzoate) and 4 [2-(8-butyl-3-ethyl-3,4,4a,5,6,8a-hexahydro-2H-chromen-6-yl)-ethyl benzoate] also have been isolated from the ethyl acetate extract of host seaweed S. myriocystum. The two compounds isolated from ethyl acetate extract of S. myriocystum with lesser antibacterial properties shared similar structures with the compounds purified from B. subtilis that suggested the ecological and metabolic relationship between these compounds in seaweed-bacterial relationship. Tetrahydropyran-2-one moiety of the tetrahydropyrano-[3,2b]-pyran-2(3H)-one system of 1 might be cleaved by the metabolic pool of seaweeds to afford methyl 3-(dihydro-3-methyl-2H-pyranyl)-propanoate moiety of 3, which was found to have no significant antibacterial activity. It is therefore imperative that the presence of dihydro-methyl-2H-pyran-2-yl propanoate system is essentially required to impart the greater activity. The direct involvement of polarisability (Pl) with the target bioactivity in 2 implied that inductive (field/polar) rather than the steric effect (parachor) appears to be the key factor influencing the induction of antibacterial activity. The present work may have a footprint on the use of novel O-heterocyclic polyketide products from seaweed-associated bacterium for biotechnological, food, and pharmaceutical applications mainly as novel antimicrobial secondary metabolites.

Caged xanthones: Potent inhibitors of global predominant MRSA USA300.

Total of 22 caged xanthones were subjected to susceptibility testing of global epidemic MRSA USA300. Natural morellic acid showed the strongest potency (MIC of 12.5µM). However, its potent toxicity diminishes MRSA therapeutic potential. We synthetically modified natural morellic acid to yield 13 derivatives (3a-3m). Synthetically modified 3b retained strong potency in MRSA growth inhibition, yet the toxicity was 20-fold less than natural morellic acid, permitting the possibility of using caged xanthones for MRSA therapeutic.

Bioactive Secondary Metabolites with Unique Aromatic and Heterocyclic Structures Obtained from Terrestrial Actinomycetes Species.

Natural products from actinomycetes are important and valuable sources for drug discovery and the development of biological tools. The present review describes our recent study on the isolation of new natural products mainly possessing heterocyclic and aromatic ring structures with biological effects on cancer-related cellular pathways such as tumor necrosis factor-α-related apoptosis-inducing ligand (TRAIL) and Wnt signaling.

Simultaneous Quantitation of Free Amino Acids, Nucleosides and Nucleobases in Sipunculus nudus by Ultra-High Performance Liquid Chromatography with Triple Quadrupole Mass Spectrometry.

To evaluate the nutritional and functional value of Sipunculus nudus, a rapid, simple and sensitive analytical method was developed using ultra-high performance liquid chromatography coupled with a triple quadrupole mass detection in multiple-reaction monitoring mode for the simultaneous quantitative determination of 25 free amino acids and 16 nucleosides and nucleobases in S. nudus within 20 min, which was confirmed to be reproducible and accurate. The limits of detection (LODs) and quantification (LOQs) were between 0.003-0.229 µg/mL and 0.008-0.763 µg/mL for the 41 analytes, respectively. The established method was applied to analyze 19 batches of S. nudus samples from four habitats with two different processing methods. The results showed that S. nudus contained a variety of free amino acids, nucleosides and nucleobases in sufficient quantity and reasonable proportion. They also demonstrated that the contents of these compounds in different parts of S. nudus were significantly discriminating, which were in the order: (highest) coelomic fluid > body wall > intestine (lowest). The method is simple and accurate, and could serve as a technical support for establishing quality control of S. nudus and other functional seafoods. Moreover, the research results also laid foundation for further exploitation and development of S. nudus.

A Complementary Study of Mechanisms and Behaviors in Chromatography via Modeling.

Evolution in preparation of chromatographic columns has created the need for studying and evaluating them with the use of smart software. This research is an attempt to compare the retention mechanism between two stationary phases (butyl and phenyl) with the use of multivariate analysis for a large number of probes. Partial least squares has the ability to spot either major or minor differences in the chromatographic behavior of probes, with regard to changes in the stationary or mobile phases. The models developed refer to a total of 108 miscellaneous chemical compounds, described by 63 X variables (physicochemical properties and structural features) and one Y variable (retention time). The results showed that in both columns and mobile phases (40% methanol or 40% acetonitrile) the retention of an analyte is mainly affected by its lipophilicity, molar volume, and refractivity, which tend to cause delayed elution. On the contrary, solubility in water, polar surface area, and hydrogen bond donor or acceptor properties promote faster elution. The most important difference proved to be the effect of the presence of the carboxylic group and the solubility that affected the retention in a similar way in both columns but not with both mobile phases.

The homalium alkaloids: isolation, synthesis, and absolute configuration assignment.

The structurally related natural products (-)-homaline, (-)-hopromine, (-)-hoprominol, and (-)-hopromalinol have been collectively termed the homalium alkaloids. All four alkaloids possess bis-ζ-azalactam structures, but differ only by the identities of the side chain on each lactam ring. Since their isolation (from the leaves of Homalium pronyense Guillaum found in the forests of New Caledonia), there have been several syntheses of homaline, hopromine, hoprominol, and hopromalinol in both racemic and enantiopure forms. The most highly yielding and versatile strategy for their synthesis employs the conjugate addition of an enantiopure lithium amide reagent to an α,ß-unsaturated ester as the key stereodefining step. This methodology has been used in the syntheses of all four members of the homalium alkaloid family and their stereoisomers.