Formation of flavor of dry champignons (Agaricus bisporus L.)

The composition of aroma compounds of dry champignons (Agaricus bisporus L.) were identified using capillary gas chromatography and chromatography-mass spectrometry. In total, 56 compounds were identified. It was found that the flavor of dry mushrooms was formed by the volatile compounds produced as a result of enzymatic and oxidative conversion of unsaturated fatty acids as well as in the Maillard reaction. Unsaturated alcohols and ketones containing eight carbon atoms determined the mushroom note of the product. The specific aroma of dry mushrooms was determined by a complex composition of substituted sul- fur-, oxygen-, and nitrogen-containing heterocyclic compounds as well as by aliphatic carbonyl compounds and methional. It was found that the concentrations of volatile carbonylic and heterocyclic compounds increased after the addition of a mixture of amino acids to mushrooms before drying. As a result, the intensity of the aroma of dry mushrooms increased.     

Derivatives of imidazotriazine and pyrrolotriazine C-nucleosides as potential new anti-HCV agents

Previous investigations identified 2′-C-Me-branched ribo-C-nucleoside adenosine analogues, 1, which contains a pyrrolo[2,1-f][1,2,4]triazin-4-amine heterocyclic base, and 2, which contains an imidazo[2,1-f][1,2,4]triazin-4-amine heterocyclic base as two compounds with promising anti-HCV in vitro activity. This Letter describes the synthesis and evaluation of a series of novel analogues of these compounds substituted at the 2-, 7-, and 8-positions of the heterocyclic bases. A number of active new HCV inhibitors were identified but most compounds also demonstrated unacceptable cytotoxicity. However, the 7-fluoro analogue of 1 displayed good potency with a promising cytotherapeutic margin.     

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.     

Selection of microbial biocatalysts for the reduction of cyclic and heterocyclic ketones

The reduction of carbonyl compounds plays an important role in the synthesis of complex chiral molecules. In particular, enantiopure substituted cyclic and heterocyclic compounds are useful intermediates for the synthesis of several antiviral, antitumor, and antibiotic agents, and recently, they have also been used as organocatalysts for C-C addition. Alcohol dehydrogenases (ADH) are enzymes involved in the transformation of prochiral ketones to chiral hydroxyl compounds. While significant scientific effort has been paid to the use of aliphatic and exocyclic ketones as ADH substrates, reports on (hetero)cyclic carbonyl compounds as substrates of these enzymes are scarce. In the present study, 109 bacteria and 36 fungi were screened, resulting in 10 organisms belonging to both kingdoms capable of transforming cyclic and heterocyclic ketones into the corresponding alcohols. Among them, Erwinia chrysanthemi could quantitatively reduce cyclododecanone and Geotrichum candidum could stereoselectively reduce N-Boc-3-piperidone and N-Boc-3-pyrrolidinone to their corresponding (S)-alcohols; however, the anti-Prelog isomer was obtained when acetophenone was the substrate.     

Synthesis and antiplasmodial activity of new heteroaryl derivatives of 7-chloro-4-aminoquinoline

With the aim to investigate the effect of different heterocyclic rings linked to the 4-aminoquinoline nucleus on the antimalarial activity, a set of 7-chloro-N-(heteroaryl)-methyl-4-aminoquinoline and 7-chloro-N-(heteroaryl)-4-aminoquinoline was synthesized and tested in vitro against D-10 (CQ-S) and W-2 (CQ-R) strains of Plasmodium falciparum. All compounds exhibited from moderate to high antiplasmodial activities. The activity was strongly influenced both by the presence of a methylenic group, as a spacer between the 4-aminoquinoline and the heterocyclic ring, and by the presence of a basic head. The most potent molecules inhibited the growth of both CQ-S and CQ-R strains of P. falciparum with IC₅₀ < 30 nM and were not toxic against human endothelial cells. These results confirm that the presence of an heteroaryl moiety in the side chain of 7-chloro-4-aminoquinoline is useful for the design and development of new powerful antimalarial agents.     

Isolation and characterization of allelochemicals in rye herbage

Residues and aqueous extracts of rye (Secale cereale L. ‘Wheeler’) shoot herbage were previously shown to contain phytotoxic compounds. Sequential partitioning of aqueous extracts against a series of solvents of increasing polarity separated the most active compounds in the Et₂O fraction based on a cress (Lepidium sativum L. ‘Curly’) root growth assay. Bioassays after TLC indicated two major zones of toxicity. Further separation of the Et₂O extract revealed two new phytotoxic compounds in rye. The compounds were identified as 2,4-dihydroxy-1,4(2H)-benzoxazin-3-one (DIBOA) and a breakdown product 2(3H)-benzoxazolinone (BOA). In the cress bioassay, DIBOA and BOA inhibited root growth 50% or more at concentrations of ca 0.37 and 1.05 mM, respectively. Only DIBOA showed significant activity on barnyardgrass (Echinochloa crusgalli L. Beauv.). Neither compound inhibited seed germination at concentrations tested. DIBOA stimulated root and shoot growth of cress at the lowest concentration tested (0.09 mM).     

Catechol dioxygenase expression in a Pseudomonas fluorescens strain exposed to different aromatic compounds

Batch cultures of Pseudomonas fluorescens (strain P2a) maintained under carbon-limiting conditions in the presence of chrysene and other aromatics, survived starvation with no detectable changes in cell number for at least 4 months. P2a also demonstrated high dioxygenase levels after growth on benzoate and catechol. To characterize this strain further, early stationary-phase cells were resuspended in fresh mineral medium containing different aromatics, to evaluate enzyme expression in the presence of high-molecular-mass (isocyclic and heterocyclic) compounds. Results demonstrated effects on catechol 1,2-dioxygenase modulation by the model compounds used, confirming a low substrate specificity for this enzyme. The increases of specific activity observed in the presence of heterocyclic compounds were higher than those observed with isocyclic compounds. Received: 28 October 1996 / Accepted: 23 November 1996     

Growth of Pure Cultures of Marine Phytoplankton in the Presence of Toxicants

The effects of 17 toxicants on the growth of five species of algae in pure culture were studied. The two species displaying the greatest sensitivity to the action of each of the compounds tested were Monochrysis lutheri and Phaeodactylum tricornutum, and the most resistant species was Protococcus. Of eight different classes of toxicants tested, substituted urea compounds and a mercuric compound were most effective in inhibiting growth of all algal species at the lowest concentrations.     

Marqueurs Á spin construits directement sur le squelette carboné de sucres

Treatment of aldehydo-sugars with 2,3-bis(hydroxyamino)-2,3-dimethylbutane gave the corresponding 1,3-dihydroxyimidazolidines. Oxidation of these compounds gave, successively, unstable, free radicals having a 3-hydroxyimidazolidine 1-oxyl structure, then stable, free radicals having a 2-glycosyl-2-imidazoline 3-oxide 1-oxyl structure, which were reduced to stable 2-glycosyl-2-imidazoline 1-oxyl compounds. The orientation of the two last-named series of compounds around the σ bond between carbohydrate and heterocyclic residues that bears the radical centre is indicated by the value of the hyperfine coupling aH of the carbohydrate proton nearest to the nitrogenous heterocyclic residue. The study of numerous compounds of both series shows that the value of the hyperfine coupling depends greatly on the structure of the carbohydrate residue. A general explanation based on the preponderance of eclipsed forms and on the primary influence of steric hindrance due to the substituents of the carbohydrate residue is proposed. This study also gives some indirect information on the conformation of diamagnetic compounds that show little sterical difference, and about which ¹H-n.m.r. spectroscopy does not provide useful information.     

Transformation of saturated nitrogen-containing heterocyclic compounds by microorganisms

The saturated nitrogen-containing heterocyclic compounds include many drugs and compounds that may be used as synthons for the synthesis of other pharmacologically active substances. The need for new derivatives of saturated nitrogen-containing heterocycles for organic synthesis, biotechnology and the pharmaceutical industry, including optically active derivatives, has increased interest in microbial synthesis. This review provides an overview of microbial technologies that can be valuable to produce new derivatives of saturated nitrogen-containing heterocycles, including hydroxylated derivatives. The chemo-, regio- and enantioselectivity of microbial processes can be indispensable for the synthesis of new compounds. Microbial processes carried out with fungi, including Beauveria bassiana, Cunninghamella verticillata, Penicillium simplicissimum, Aspergillus niger and Saccharomyces cerevisiae, and bacteria, including Pseudomonas sp., Sphingomonas sp. and Rhodococcus erythropolis, biotransform many substrates efficiently. Among the biological activities of saturated nitrogen-containing heterocyclic compounds are antimicrobial, antitumor, antihypertensive and anti-HIV activities; some derivatives are effective for the treatment and prevention of malaria and trypanosomiasis, and others are potent glycosidase inhibitors.     

Bisquaternary pyridinium oximes: Comparison of in vitro reactivation potency of compounds bearing aliphatic linkers and heteroaromatic linkers for paraoxon-inhibited electric eel and recombinant human acetylcholinesterase

Oxime reactivators are the drugs of choice for the post-treatment of OP (organophosphorus) intoxication and used widely for mechanistic and kinetic studies of OP-inhibited cholinesterases. The purpose of the present study was to evaluate new oxime compounds to reactivate acetylcholinesterase (AChE) inhibited by the OP paraoxon. Several new bisquaternary pyridinium oximes with heterocyclic linkers along with some known bisquaternary pyridinium oximes bearing aliphatic linkers were synthesized and evaluated for their in vitro reactivation potency against paraoxon-inhibited electric eel acetylcholinesterase (EeAChE) and recombinant human acetylcholinesterase (rHuAChE). Results herein indicate that most of the compounds are better reactivators of EeAChE than of rHuAChE. The reactivation potency of two different classes of compounds with varying linker chains was compared and observed that the structure of the connecting chain is an important factor for the activity of the reactivators. At a higher concentration (10^?3 M), compounds bearing aliphatic linker showed better reactivation than compounds with heterocyclic linkers. Interestingly, oximes with a heterocyclic linker inhibited AChE at higher concentration (10^?3 M), whereas their ability to reactivate was increased at lower concentrations (10^?4 M and 10^?5 M). Compounds bearing either a thiophene linker 26, 46 or a furan linker 31 showed 59%, 49% and 52% reactivation of EeAChE, respectively, at 10^?5 M. These compounds showed 14%, 6% and 15% reactivation of rHuAChE at 10^?4 M. Amongst newly synthesized analogs with heterocyclic linkers (26–35 and 45–46), compound 31, bearing furan linker chain, was found to be the most effective reactivator with a k_r 0.042 min^?1, which is better than obidoxime (3) for paraoxon-inhibited EeAChE. Compound 31 showed a k_r 0.0041 min^?1 that is near equal to pralidoxime (1) for paraoxon-inhibited rHuAChE.     

Lignin Peroxidase Oxidation of Aromatic Compounds in Systems Containing Organic Solvents

Lignin peroxidase from Phanerochaete chrysosporium was used to study the oxidation of aromatic compounds, including polycyclic aromatic hydrocarbons and heterocyclic compounds, that are models of moieties of asphaltene molecules. The oxidations were done in systems containing water-miscible organic solvents, including methanol, isopropanol, N, N-dimethylformamide, acetonitrile, and tetrahydrofuran. Of the 20 aromatic compounds tested, 9 were oxidized by lignin peroxidase in the presence of hydrogen peroxide. These included anthracene, 1-, 2-, and 9-methylanthracenes, acenaphthene, fluoranthene, pyrene, carbazole, and dibenzothiophene. Of the compounds studied, lignin peroxidase was able to oxidize those with ionization potentials of <8 eV (measured by electron impact). The reaction products contain hydroxyl and keto groups. In one case, carbon-carbon bond cleavage, yielding anthraquinone from 9-methylanthracene, was detected. Kinetic constants and stability characteristics of lignin peroxidase were determined by using pyrene as the substrate in systems containing different amounts of organic solvent. Benzyl alkylation of lignin peroxidase improved its activity in a system containing water-miscible organic solvent but did not increase its resistance to inactivation at high solvent concentrations.     

Synthesis and reactions of some new pyrrolylthieno[2,3-D]quinoxaline and pyrrolopyrazinothienoquinoxalines

The synthesis of 3-pyrrolyl-2-substituted thieno[2,3-b]quinoxalines from the precursor 3-amino derivatives are described. Synthesized compounds were subjected to reactions with other reagents to synthe-size polyfused heterocyclic incorporated thienoquinoxaline moiety. Some of the synthesized compounds were screened for their antibacterial and antifungal activities.     

The Marine Isolate <Emphasis Type="Italic">Novosphingobium</Emphasis> sp. PP1Y Shows Specific Adaptation to Use the Aromatic Fraction of Fuels as the Sole Carbon and Energy Source

Novosphingobium sp. PP1Y, isolated from a surface seawater sample collected from a closed bay in the harbour of Pozzuoli (Naples, Italy), uses fuels as its sole carbon and energy source. Like some other Sphingomonads, this strain can grow as either planktonic free cells or sessile-aggregated flocks. In addition, this strain was found to grow as biofilm on several types of solid and liquid hydrophobic surfaces including polystyrene, polypropylene and diesel oil. Strain PP1Y is not able to grow on pure alkanes or alkane mixtures but is able to grow on a surprisingly wide range of aromatic compounds including mono, bi, tri and tetracyclic aromatic hydrocarbons and heterocyclic compounds. During growth on diesel oil, the organic layer is emulsified resulting in the formation of small biofilm-coated drops, whereas during growth on aromatic hydrocarbons dissolved in paraffin the oil layer is emulsified but the drops are coated only if the mixtures contain selected aromatic compounds, like pyrene, propylbenzene, tetrahydronaphthalene and heterocyclic compounds. These peculiar characteristics suggest strain PP1Y has adapted to efficiently grow at the water/fuel interface using the aromatic fraction of fuels as the sole carbon and energy source.     

Searching for multi-target antipsychotics: Discovery of orally active heterocyclic N-phenylpiperazine ligands of D2-like and 5-HT1A receptors

We described herein the design, synthesis, and pharmacological evaluation of N-phenylpiperazine heterocyclic derivatives as multi-target compounds potentially useful for the treatment of schizophrenia. The isosteric replacement of the heterocyclic ring at the biaryl motif generating pyrazole, 1,2,3-triazole, and 2-methylimidazole[1,2-a]pyridine derivatives resulted in 21 analogues with different substitutions at the para-biaryl and para-phenylpiperazine positions. Among the compounds prepared, 4 (LASSBio-579) and 10 (LASSBio-664) exhibited an adequate binding profile and a potential for schizophrenia positive symptoms treatment without cataleptogenic effects. Structural features of this molecular scaffold are discussed regarding binding affinity and selectivity for D₂-like, 5-HT_1A, and 5-HT_2A receptors.     

Intramolecular catalysis of amide hydrolysis by carboxyl and metal ion/proton agents: I. Intramolecular reactions of imidazole or pyridine derivatives of maleamic acid

Kinetic studies on the hydrolysis of N-(2-imidazolylethyl)maleamic acid, N-(2-pyridylethyl)maleamic acid, and N-(2-pyridylmethyl)maleamic acid were carried out. In these maleamic acid derivatives, the amide nitrogens together with the heterocyclic nitrogens form bidentate ligands. The compounds were hydrolyzed through nucleophilic catalysis by carboxyl groups. The pH profiles for the hydrolysis at 65°C were descending sigmoids and were unaffected by the ionization of the heterocyclic nitrogens. The absence of rate enhancement due to the added divalent metal ions revealed that chelate formation by the bidentate leaving groups is not efficient. N-(2-Pyridylmethyl)maleamic acid underwent a dual intramolecular nucleophilic reaction through participation of both the carboxyl and the pyridyl groups.     

New heterocyclic compounds from Ranunculus ternatus Thunb.

Five new heterocyclic compounds, 5-α-d-fructofuranosylmethyl-furfural (1), 5-β-d-fructofuranosylmethyl-furfural (2), 5-β-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.     

Glucosamine-6-phosphate synthase inhibiting C3-β-cholesterol tethered spiro heterocyclic conjugates: Synthesis and their insight of DFT and docking study

A series of novel covalent cholesterol-spiro pyrrolidine/pyrrolizidine heterocyclic hybrids possessing biologically active oxindole, indanedione, and acenaphthylene-1-one have been synthesized by the reaction of C3-β-cholesteroalacrylate with heterocyclic di- and tri-ketones. All the sixteen compounds were obtained as a single isomer in good yield through a stereo- and regio- selective 1,3-dipolar cycloaddition methodology. Stereochemistry of the spiranic cycloadducts has been established by spectroscopic analysis and the regioselectivity outcome of the spiro adducts has been accomplished by DFT calculations at B3LYP/6-31G (d,p) level study. In vitro antibacterial activity of the newly synthesized cycloadducts were evaluated against highly pathogenic Gram-positive and Gram-negative bacteria and the most active compounds 5a, 13, and 14 underwent automated in silico molecular docking analysis in order to validate their effective orientation as a inhibitors bound in the active site of glucosamine-6-phosphate synthase (1XFF) enzyme by employing AutoDock Tools.     

Discovery of hydroxy pyrimidine Factor IXa inhibitors

The synthesis and structure activity relationship development of a pyrimidine series of heterocyclic Factor IXa inhibitors is described. Increased selectivity over Factor Xa inhibition was achieved through SAR expansion of the P1 element. Select compounds were evaluated in vivo to assess their plasma levels in rat.     

Structural characterization and DNA interactions of new cytotoxic transplatin analogues containing one planar and one nonplanar heterocyclic amine ligand

trans-Diaminedicholoroplatinum(II) complexes with one planar and one non-planar heterocyclic amine ligand were designed as new potential antitumor drugs. The X-ray crystallographic structures of trans-[PtCl₂(4-picoline)(piperidine)] and trans-[PtCl₂(4-picoline)(piperazine)]·HCl revealed that the piperidine and piperazine ligands bind to the platinum through the equatorial position and that the ligands adopt the chair conformation. The nonplatinated amine of the piperazine can form hydrogen bonds with atoms that are approximately 7.5 Å away from the Pt binding site. DNA is considered a major pharmacological target of platinum compounds. Hence, to expand the database correlating structural features of platinum compounds and DNA distortions induced by these compounds, which may facilitate identification of more effective anticancer platinum drugs, we describe the DNA binding mode in a cell-free medium of trans-[PtCl₂(4-picoline)(piperidine)] and trans-[PtCl₂(4-picoline)(piperazine)]·HCl. Interestingly, the overall impact of the replacement of the second ammine group in transplatin by the heterocyclic ligands appears to change the character of the global conformational changes induced in DNA towards that induced by cisplatin. The clinical ineffectiveness of the parent transplatin has been proposed to be also associated with its reduced capability to form bifunctional adducts in double-helical DNA. The results of the present work support the view that replacement of both ammine groups of transplatin by heterocyclic ligands enhances cytotoxicity probably due to the marked enhancement of the stability of intrastrand cross-links in double-helical DNA.