Aromatic Heterocyclic Derivatives Research Articles

LA multiple PAHs-degrading Shinella sp. strain and its potential bioremediation in wastewater

Polycyclic aromatic hydrocarbons (PAHs) and heterocyclic derivatives are organic pollutants which threaten ecosystems and human beings. In this study, a new strain, Shinella sp. FLN 14, was isolated and characterized. It can utilize fluorene as its sole carbon source and effectively co-metabolize multiple PAHs and heterocyclic derivatives, including phenanthrene, acenaphthene, and fluoranthene. Two possible metabolic pathways are proposed (i.e., salicylic acid pathway and phthalic acid pathway). Whole-genome sequencing revealed that strain FLN14 possesses a chromosome and four plasmids. However, when combined with ensemble genetic information, novel fluorene-degrading functional gene clusters were not located within the genome of FLN 14, except for some new dioxygenases and electron transport chains, which typically initiate the oxidation of aromatic compounds. In wastewater bioremediation, strain FLN14 removed nearly 95 % of PAHs within 5 days and maintained high degrading activity during the 18-day reaction compared to the control. Overall, our study provides a promising candidate to achieve bioremediation of PAHs-contaminated environments.

Synthesis and Antiplasmodial Activity of Novel Bioinspired Imidazolidinedione Derivatives.

Malaria is an enormous threat to public health, due to the emergence of Plasmodium falciparum resistance to widely-used antimalarials, such as chloroquine (CQ). Current antimalarial drugs are aromatic heterocyclic derivatives, most often containing a basic component with an added alkyl chain in their chemical structure. While these drugs are effective, they have many side effects. This paper presents the synthesis and preliminary physicochemical characterisation of novel bioinspired imidazolidinedione derivatives, where the imidazolidinedione core was linked via the alkylene chain and the basic piperazine component to the bicyclic system. These compounds were tested against the asexual stages of two strains of P. falciparum—the chloroquine-sensitive (D10) and chloroquine-resistant (W2) strains. In parallel, in vitro cytotoxicity was investigated on a human keratinocyte cell line, as well as their hemolytic activity. The results demonstrated that the antiplasmodial effects were stronger against the W2 strain (IC50 between 2424.15–5648.07 ng/mL (4.98–11.95 µM)), compared to the D10 strain (6202.00–9659.70 ng/mL (12.75–19.85 µM)). These molecules were also non-hemolytic to human erythrocytes at a concentration active towards the parasite, but with low toxicity to mammalian cell line. The synthetized derivatives, possessing enhanced antimalarial activity against the CQ-resistant strain of P. falciparum, appear to be interesting antimalarial drug candidates.

A Pseudomonas sp. strain uniquely degrades PAHs and heterocyclic derivatives via lateral dioxygenation pathways

Polycyclic aromatic hydrocarbons (PAHs) and heterocyclic derivatives are organic pollutants that pose a serious health risk to human beings. In this study, a newly isolated Pseudomonas brassicacearum strain MPDS could effectively degrade PAHs and heterocyclic derivatives, including naphthalene, fluorene, dibenzofuran (DBF) and dibenzothiophene (DBT). Notably, strain MPDS is able to degrade fluorene, DBF and DBT uniquely via a lateral dioxygenation pathway, while most reported strains degrade fluorene, DBF and DBT via an angular dioxygenation pathway or co-metabolize them via a lateral dioxygenation pathway. Strain MPDS completely degraded 50 mg naphthalene (in 50 mL medium) in 84 h, and OD600 reached 1.0–1.1; while, it stabilized at OD600 0.5–0.6 with 5 mg fluorene or DBF or DBT. Meanwhile, 65.7% DBF and 32.1% DBT were degraded in 96 h, and 40.3% fluorene was degraded in 72 h, respectively. Through genomic and transcriptomic analyses, and comparative genomic analysis with another DBF degradation strain, relevant gene clusters were predicted, and a naphthalene-degrading gene cluster was identified. This study provides understanding of degradation of PAHs and their heterocyclic derivatives, as well as new insights into the lateral dioxygenation pathway of relevant contaminants.

Controllable Synthesis of Polyheterocyclic Spirooxindoles and 3,3‐Bistryptophol Oxindoles via Fe(ClO4)3 ⋅ 6H2O‐Promoted Hetero‐Pictet‐Spengler Reaction

AbstractAn efficient Fe(ClO4)3 ⋅ 6H2O‐promoted hetero‐Pictet‐Spengler reaction has been developed, enabling divergent approaches to plenty of structurally diverse polyheterocyclic spirooxindoles and 3,3‐bistryptophol oxindoles from readily available isatins and substituted aromatic heterocyclic derivatives in up to 98% yield. Mechanistic investigation reveals that the perchloric acid generated upon on hydrolysis of Fe(ClO4)3 ⋅ 6H2O by residual water was the real catalyst. The synthetic robustness of this transformation is demonstrated by the friendly, easy handling of the catalyst and the controllable access of diverse privileged heterocyclic skeletons.magnified image

Design, synthesis and evaluation of aromatic heterocyclic derivatives as potent antifungal agents

To further enhance the anti-Aspergillus efficacy of our previously discovered antifungal lead compounds (1), a series of aromatic heterocyclic derivatives were designed, synthesized and evaluated for in vitro antifungal activity. Many of the target compounds showed good inhibitory activity against Candida albicans and Cryptococcus neoformans. In particular, the isoxazole nuclei were more suited for improving the activity against Aspergillus spp. Among these compounds, 2-F substituted analogues 23g and 23h displayed the most remarkable in vitro activity against Candida spp., C. neoformans, A. fumigatus and fluconazole-resistant C.alb. strains, which is superior or comparable to the activity of the reference drugs fluconazole and voriconazole. Notably, the compounds 23g and 23h exhibited low inhibition profiles for various isoforms of human cytochrome P450 and excellent blood plasma stability.

Comparisons on isomeric 1,10-phenanthroline aromatic heterocyclic derivatives with triphenylamine and thiophene donors before and after rhenium(I) carbonyl complexation

We have described herein a series of unsymmetric 1,10-phenanthroline (phen) based aromatic heterocyclic derivatives with triphenylamine (TPA) and thiophene donors (L1–L5) and their respective neutral tricarbonyl rhenium(I) complexes (6a–6e). Comparisons between isomeric compounds L1/L2 and 6a/6b as well as L3/L4/L5 and 6c/6d/6e have been made on their 1H NMR and UV/Vis spectra, single-crystal structures and density function theory (DFT) calculations. The alterations of conjugated system of the whole molecules, originating from the introduction of 2-, 3- or 3,8-substituted TPA and thiophene groups of phen, are responsible for the structural and spectral discrepancy of these structural isomers. In particular, the introduction of TPA and/or thiophene donors at 2-postion of phen (L1 and L3) leads to smaller band gaps than their respective 3-substituted isomers (L2 and L4). In addition, rhenium(I) ion complexation could slightly lower the highest occupied molecular orbital (HOMO) energy levels but significantly decrease the lowest unoccupied molecular orbital (LUMO) energy levels of the molecular system.

Synthesis and Characterization of Aromatic-Heterocyclic Derivatives of Sulphonamides as Potential Antimicrobial Agents

The incidence of microbial infection is increasing world-wide despite active research on the discovery and development of novel anti-microbial agents. Then emergence of multi-resistant strains of bacteria has increased the problem of drug resistance dramatically. The development and use of new anti-microbial agents is one of the ways to combat the emergence of anti-microbial resistance. The literature survey reveals that the sulfonamide derivatives as privileged pharmacophore for wide range of biological activities including anti-microbial activity. So a series of (3a-3e and 6a-6c) sulfonamide derivatives were synthesized by attaching alkyl/ aryl/heterocyclic sulphonyl chloride and alkyl/aryl carbonyl chloride moieties to aromatic sulfonamide incorporating free amino group by Schotten Baumann (SB) reaction. All the synthesized compounds were characterized by FTIR, Mass, and other analytical techniques. The synthesized compounds have been screened against different bacterial (B. subtilis, S. aureus and E. coli) and fungal (A. niger and P. chrysogenum) strains using the cup-plate method. The synthesized sulfonamides derivatives showed significant antibacterial activity against Gram-positive and Gram-negative organisms, while they were found to be inactive against fungal strains. From the results, it is evident that the presence of a hetero/aromatic ring showed good antibacterial activity. Some of these compounds can be considered as potential candidates for treatment of infections caused by Gram-positive as well as Gram-negative bacteria.

The Influence of Process Conditions on the Chemical Composition of Pine Wood Catalytic Pyrolysis Oils

Pine wood samples were used as model feedstock to study the properties of catalytic fast pyrolysis oils. The influence of two commercial zeolite catalysts (BASF and SudChem) and pretreatment of the pine wood with sodium hydroxide on pyrolysis products were investigated. The pyrolysis oils were first fractionated using column chromatography and characterized using GC-MS. Long chain aliphatic hydrocarbons, levoglucosan, aldehydes and ketones, guaiacols/syringols, and benzenediols were the major compounds identified in the pyrolysis oils. The catalytic pyrolysis increased the polycyclic hydrocarbons fraction. Significant decreases in phthalate derivatives using SudChem and long chain aliphatics using BASF catalyst were observed. Significant amounts of aromatic heterocyclic hydrocarbons and benzene derivatives were formed, respectively, using BASF and SudChem catalysts. Guaiacyl/syringyl and benzenediols derivatives were partly suppressed by the zeolite catalysts, while the sodium hydroxide treatment enriched phenolic derivatives. Zeolite catalyst and sodium hydroxide were employed together; they showed different results for each catalyst.

The influence of the structure of some aromatic heterocyclic derivatives on their retention in reversed-phase high-performance liquid chromatography

The chromatographic behavior of aromatic heterocyclic derivatives in reversed-phase high-performance liquid chromatography was investigated. The retention characteristics of the substances under the conditions of chromatography with water-acetonitrile mobile phases (retention factors, relative retentions, distribution coefficients, Henry adsorption constants, differences in the differential molar energy of sorption, and Gibbs energies of sorption) were determined. It was shown that the chromatographic retention of the sorbates depended on their molecular structure. The influence of the nature of heteroatoms and their number on the sorption of heterocyclic compounds was discussed.

ChemInform Abstract: Synthesis, Fluorescence Properties and Biological Activity of 8‐Hydroxyquinoline Conjugate Bonded Aromatic Heterocyclic Derivatives.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Synthesis, Fluorescence Properties and Biological Activity of 8‐Hydroxyquinoline Conjugate Bonded Aromatic Heterocyclic Derivatives

AbstractFour kinds of 8‐hydroxyquinoline conjugate bonded aromatic heterocyclic derivatives were designed and synthesized for potential use in the emission and electron conduction layers in organic light emitting devices, and as luminescent probes for metal ions. These novel compounds were characterized by IR, 1H NMR, 13C NMR, Mass and UV‐visible spectra. The photoluminescent properties of the new compounds including the spectra (shape of bands, λex, λem), quantum yield (ϕf) and lifetime (τ) were investigated. Moreover, density functional theory method was used to study the relationship between the geometric configuration and emission wavelength. MTT assays of cell proliferation of rMSC and DPPH radical‐scavenging tests suggested that the new compounds generate a significant increase of rMSC and demonstrate a good antioxidant activity.

LIV-3D-QSAR models for PGI 2 receptor ligands using multiple conformations

A new 3D descriptor, the local intersection volume (LIV), was developed by our group and applied to the construction of 3D-QSAR models for ligands of the PGI 2 receptor (IP). The target compounds are a set of 42 aromatic heterocyclic derivatives [Meanwell et al., J. Med. Chem. 36 (1993), 3884], which show agonist activities in the IP receptor and are inhibitors of platelet aggregation. The LIV-3D-QSAR models were obtained through the analysis of 30% of the generated conformations for each compound, using a combined Genetic Algorithm (GA) and Partial Least Square (PLS) approach [Rogers and Hopfinger, J. Inf. Comput. Sci. 34 (1994) 854]. Statistically, Model 3 is the best as well as the most comprehensive in a mechanistic sense. Furthermore, it can be applied to design new IP ligands.

Improgan-like Analgesics: A Family of Compounds Derived From Histamine Anatgonists

The a ntinociceptive activity of some c entrally-administered H 2 antagonists has led to the development of improgan-like analgesics, which produce powerful suppression of pain responses when injected into the brain. Although selected H 2 and H 3 antagonists have antinociceptive activity, structure-activity studies and other results have shown that blockade of neither receptor accounts for the pain-relieving properties of these drugs. Although improgan does not act through known histamine or opioid receptors, and over 60 receptors and ion channels have been excluded as targets for improgan action, the mechanism of action of improgan remains unknown. In vivo studies have shown that improgan activates non-opioid, descending, pain-relieving circuits in both the periaqueductal gray and raphe magnus. These circuits use brain stem CB 1 receptors and spinal alpha2 adrenergic receptors, but improgan does not act directly at these receptor sites. New findings show that a variety of aromatic heterocyclic derivatives in this series can produce potent antinociception. However, all such compounds in this series may not be acting by identical mechanisms. Development of more potent, brain-penetrating derivatives may lead to the discovery of effective non-opioid analgesics.

Parallel synthesis of novel heteroaromatic acromelic acid analogues from kainic acid.

A range of new C-4 heteroaromatic acromelic acid analogues has been synthesized in a parallel fashion from (-)-alpha-kainic acid 1. Protection of the amine and carboxylate groups of 1 followed by ozonolysis gave methyl ketone 8. A silyl enol ether 9, generated regiospecifically from the methyl ketone 8 using "kinetic" conditions, was brominated in situ with phenyltrimethylammonium perbromide to give the key alpha-bromo ketone 10. Parallel cyclization reactions of bromo ketone 10 with thioamides and thioureas were then performed. The aromatic heterocyclic derivatives 11a-d and 19 produced were deprotected to give the new kainoid amino acids 6a-d and 25 in excellent yield. Compounds 6a and 6c show strong binding to the kainate receptor. Reaction of 10 with alternative condensing agents was also briefly investigated.

Design and synthesis of a novel class of thrombin inhibitors incorporating heterocyclic dipeptide surrogates

Several potent and selective inhibitors of thrombin incorporating novel heterocyclic peptide surrogates in the P 3-P 2 position of peptidyl argininals have been discovered. Illustrated in this article are three classes of heterocycles: pyridones, uracils, and pyrimidinones. The synthesis and biological activities of these unique aromatic heterocyclic derivatives are reported herein.

Ferro- and antiferromagnetic intermolecular interactions in the aromatic heterocyclic derivatives of α-nitronyl nitroxide

Magnetization isotherms up to 5.5 T and temperature dependence of magnetic susceptibility down to 1.8 K of the organic neutral radicals, 3- and 4-quinolyl nitronyl nitroxide and 2,6-pyridinediyl bis(nitronyl nitroxide), are described. 3-quinolyl nitronyl nitroxide exhibit ferromagnetic intermolecular interaction with the Weiss constant Θ = 0.27 K, whereas 4-quinolyl nitronyl nitroxide shows antiferromagnetic intermolecular interaction with the exchange coupling constant J/k = −7.8 K. This significant difference between the magnetic properties of two compounds are discussed in terms of their crystal structures. The temperature dependence of product of paramagnetic susceptibility and temperature, χ pT, of a biradical 2,6-pyridinediyl bis(nitronyl nitroxide) shows a plateau at low temperatures in addition to the usual plateau observed in the high-temperature region. This peculiar behavior is interpreted in terms of the multi-spin system associated with a combined effect of ferro- and antiferro-magnetic couplings.

Gas chromatographic study of donor-acceptor complexes II. Associations between aromatic heterocyclic derivatives and dibutyltetrachlorophthalate

Gas-Liquid Chromatography has been used to study the complexing reactions between dibutyltetrachlorophthalate (electron acceptor) and five-membered heterocyclic derivatives (electron donors). On the basis of theoretical equations previously derived, equilibrium constants and thermodynamic functions of reactions are calculated in the two cases where a single 1/1 complex is formed (furan and thipohene derivatives) and where two successive 1/1 and 1/2 associations occur (pyrrole derivatives). Excellent agreement is observed between the experimental results and the theoretical predictions. The results are discussed in relation with the electron donor ability of the derivatives and with the inductive and mesomeric effects of the substituents. An aromaticity scale established from equilibrium constants values is in good agreement with the results of nuclear magnetic measurements.