Pyrazine Derivatives Research Articles

Two reaction modes of 1-sulfonyl-1,2,3-triazoles and pyridinium 1,4-zwitterionic thiolates: catalyst-free synthesis of pyrido[1,2-a]pyrazine derivatives and 1,4-thiazine derivatives

Efficient catalyst-free synthesis of pyrido[1,2-a]pyrazine and 1,4-thiazine derivatives from triazole and pyridinium 1,4-zwitterionic thiolate was realized.

Synthesis of 3-Trifluoromethyl-5,6-dihydro-[1,2,4]triazolo Pyrazine Derivatives and Their Anti-Cancer Studies

The synthesis of a wide variety of 3-trifluoromethyl-5,6-dihydro-[1,2,4]triazolo pyrazine derivatives, by the treatment of 3-trifluoromethyl-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-α]pyrazine hydrochloride with an array of isocyanates in the presence of triethylamine, is reported. All the target compounds were synthesized in excellent yields under mild reaction conditions. The target molecules were effectively screened for their anti-cancer properties and the results are promising. The resultant compounds were assessed for their antiproliferative action against two human colon cancer cell lines (HCT-116 and HT-29 colon cancer cell lines). The IC50 range was estimated at 6.587 to 11.10 µM showing that compound RB7 had remarkable anticancer movement on HT-29. Additionally, it was discovered that RB7 incited the mitochondrial apoptotic pathway by up-regulating Bax and down-regulating Bcl2, eventually leading to the activation of Caspase 3 in HT-29 cells and initiation of cell death via the mitochondrial apoptotic pathway.

Imidazo[1,2-a]quinoxalines for melanoma treatment with original mechanism of action.

The malignant transformation of melanocytes causes several thousand deaths each year, making melanoma an important public health concern. Melanoma is the most aggressive skin cancer, which incidence has regularly increased over the past decades. We described here the preparation of new compounds based on the 1-(3,4-dihydroxyphenyl)imidazo[1,2-a]quinoxaline structure. Different positions of the quinoxaline moiety were screened to introduce novel substituents in order to study their influence on the biological activity. Several alkylamino or alkyloxy groups were also considered to replace the methylamine of our first generation of Imiqualines. Imidazo[1,2-a]pyrazine derivatives were also designed as potential minimal structure. The investigation on A375 melanoma cells displayed interesting invitro low nanomolar cytotoxic activity. Among them, 9d (EAPB02303) is particularly remarkable since it is 20 times more potent than vemurafenib, the reference clinical therapy used on BRAF mutant melanoma. Contrary to the first generation, EAPB02303 does not inhibit tubulin polymerization, as confirmed by an invitro assay and a molecular modelisation study. The mechanism of action for EAPB02303 highlighted by a transcriptomic analysis is clearly different from a panel of 12 well-known anticancer drugs. InvivoEAPB02303 treatment reduced tumor size and weight of the A375 human melanoma xenografts in a dose-dependent manner, correlated with a low mitotic index but not with necrosis.

In silico studies on pyrazine derivatives for identifying potential inhibitors of PIM-1 kinase

PIM-1 kinase (PIM-1K) modulates multiple cellular functions and is evolving as a drug target for cancer. In search of potential PIM-1 inhibitors, we report herein the 3D-QSAR as well as docking studies on 3-(pyrazin-2-yl)-1H-indazole derivatives. Based on the 3D-QSAR study, the generated pharmacophore was utilized for the virtual screening of thousands of compounds (compds) from ZINC database against PIM-1K. Four top-ranked compds, ZINC05885218, ZINC05888770, ZINC08652441, and ZINC73096248, were selected by virtual screening study. The study results of molecular docking suggested that certain key residues were significant for interactions of ligand–receptor due to the formation of hydrogen bonds with Glu171, Glu121, Lys67, Asp128, Asp131 and Asp186 of PIM-1K. Virtually screened compds displayed resemblance in binding interactions within the PIM-1Ks catalytic pocket in comparison with their corresponding crystal structures. The ADRRR.2 emerged as the potential pharmacophore hypothesis and was employed for the generation of model of 3D-QSAR which gave good statistical values of q2 and r2 using partial least square analyses (r2 = 0.922, q2 = 0.8629) for the best model. The study results revealed that ZINC73096248 could serve as a prototype compd for developing novel PIM-1K inhibitors.

"Metal-Free" Nanoassemblies of AIEE-ICT-Active Pyrazine Derivative: Efficient Photoredox System for the Synthesis of Benzimidazoles.

Supramolecular nanoassemblies of an AIEE-ICT-active pyrazine derivative (TETPY) having strong absorption in the visible region and excellent transportability have been utilized as an efficient photoredox catalytic system for the synthesis of a variety of benzimidazoles having electron-withdrawing/electron-releasing/aliphatic groups under "metal-free" conditions. The reaction protocol involves the successful harvesting of visible light by TETPY assemblies to catalyze the coupling of o-phenylenediamine/substituted diamines and substituted aromatic/heterocyclic/aliphatic aldehydes under aerial conditions using mixed aqueous media as the reaction solvent. TETPY assemblies could activate aerial oxygen to generate superoxide for completing the vital proton abstraction step without the need for any external metal/base/oxidant. Moreover, all the products are purified by recrystallization from organic solvents. The TETPY assemblies also exhibited high efficiency in catalyzing the synthesis of 2-substituted benzothiazoles and quinazolines in excellent yields.

Clean Grinding Technique: A Facile Synthesis and In Silico Antiviral Activity of Hydrazones, Pyrazoles, and Pyrazines Bearing Thiazole Moiety against SARS-CoV-2 Main Protease (Mpro).

A novel series of some hydrazones bearing thiazole moiety were generated via solvent-drop grinding of thiazole carbohydrazide 2 with various carbonyl compounds. Also, dehydrative-cyclocondensation of 2 with active methylene compounds or anhydrides gave the respective pyarzole or pyrazine derivatives. The structures of the newly synthesized compounds were established based on spectroscopic evidences and their alternative syntheses. Additionally, the anti-viral activity of all the products was tested against SARS-CoV-2 main protease (Mpro) using molecular docking combined with molecular dynamics simulation (MDS). The average binding affinities of the compounds 3a, 3b, and 3c (−8.1 ± 0.33 kcal/mol, −8.0 ± 0.35 kcal/mol, and −8.2 ± 0.21 kcal/mol, respectively) are better than that of the positive control Nelfinavir (−6.9 ± 0.51 kcal/mol). This shows the possibility of these three compounds to effectively bind to SARS-CoV-2 Mpro and hence, contradict the virus lifecycle.

Second-order nonlinear optical properties of [formula omitted]-shaped pyrazine derivatives

The linear and nonlinear optical (NLO) properties of a series of Λ-shaped derivatives containing a 4,5-dicyanopyrazine acceptor unit, N,N-dimethylamino donor groups and systematically enlarged π-conjugated linkers are investigated by means of UV/Visible and Hyper-Rayleigh scattering spectroscopies. Density functional theory calculations are also carried out to rationalize the magnitude and symmetry of the NLO responses. The results demonstrate that these compounds possess two low-lying excited electronic states close to each other in energy, which are accessible through one-photon optical transitions respectively polarized perpendicular and parallel to the two-fold molecular axis. These two states contribute additively to the first hyperpolarizability, which exhibits a dominant dipolar character. We also show that the NLO responses significantly deviate from Kleinman's index permutation symmetry.

Tetrahydroimidazo[1,2‐a]pyrazine Derivatives: Synthesis and Evaluation as Gαq‐Protein Ligands

The 5,6,7,8‐tetrahydroimidazo[1,2‐a]pyrazine derivative BIM‐46174 and its dimeric form BIM‐46187 (1) are heterocyclized dipeptides that belong to the very few cell‐permeable compounds known to preferentially silence Gαq proteins. To explore the chemical space of Gαq inhibitors of the BIM chemotype, a combinatorial approach was conducted towards a library of BIM molecules. This library was evaluated in a second messenger‐based fluorescence assay to analyze the activity of Gαq proteins through the determination of intracellular myo‐inositol 1‐phosphate. Structure–activity relationships were deduced and structural requirements for biological activity obtained, which were (i) a redox reactive thiol/disulfane substructure, (ii) an N‐terminal basic amino group, (iii) a cyclohexylalanine moiety, and (iv) a bicyclic skeleton. Active compounds exhibited cellular toxicity, which was investigated in detail for the prototypical inhibitor 1. This compound affects the structural cytoskeletal dynamics in a Gαq/11‐independent manner.

Bivariate Metal-Organic Frameworks with Tunable Spin-Crossover Properties.

In this work, pyrazine (A), aminopyrazine (B), quinoxaline (C), and 5,6,7,8-tetrahydroquinoxaline (D) have been screened out among a large number of pyrazine derivatives to construct Hofmann-type metal-organic frameworks (MOFs) Fe(L)[M(CN)4 ] (M=Pt, Pd) with similar 3D pillared-layer structures. X-ray single-crystal diffraction reveals that the alternate linkage between M and FeII ions through cyano bridges forms the 2D extended metal cyanide sheets, and ligands A-D acted as vertical columns to connect the 2D sheets to give 3D pillared-layer structures. Subsequently, a series of bivariate MOFs were constructed by pairwise combination of the four ligands A-D, which were confirmed by 1 H NMR, PXRD, FTIR, and Raman spectroscopy. The results demonstrated that ligand size and crystallization rate play a dominant role in constructing bivariate Hofmann-type MOFs. More importantly, the spin-crossover (SCO) properties of the bivariate MOFs can be finely tuned by adjusting the proportion of the two pillared ligands in the 3D Hofmann-type structures. Remarkably, the spin transition temperatures, Tc ↑ and Tc ↓ of Fe(A)x (B)1-x [Pt(CN)4 ] (x=0 to 1) can be adjusted from 239 to 254 K and from 248 to 284 K, respectively. Meanwhile, the width of the hysteresis loops can be widened from 9 to 30 K. Changing Pt to Pd, the hysteresis loops of Fe(A)x (B)1-x [Pd(CN)4 ] can be tuned from 9 (Tc ↑=215 K, Tc ↓=206 K) to 24 K (Tc ↑=300 K, Tc ↓=276 K). This research provides wider implications in the development of advanced bistable materials, especially in precisely regulating SCO properties.

Roasting and Cryogenic Grinding Enhance the Antioxidant Property of Sword Beans (Canavalia gladiata).

The objective of this study was to optimize the conditions for enhancing the antioxidant properties of sword bean (Canavalia gladiata) as a coffee substitute in two processing methods, roasting and grinding. The optimum conditions for removing off-flavor of the bean and maximizing functionality and efficiency were light roasting and cryogenic grinding (< 53 μm). In these conditions, extraction yield was 16.75%, total phenolic content (TPC) was 69.82 ± 0.35 mg gallic acid equivalents/g, and total flavonoid content (TFC) was 168.81 ± 1.64 mg quercetin equivalents/100 g. The antioxidant properties were 77.58 ± 0.27% for DPPH radical scavenging activity and 58.02 ± 0.76 mg Trolox equivalents/g for ABTS radical scavenging activity. The values for TFC and ABTS radical scavenging activity were significantly higher (p < 0.05) than in other conditions, and TPC and DPPH radical scavenging activity were second highest in lightly roasted beans, following raw beans. HS-SPME/GCMS analysis confirmed that the amino acids and carbohydrates, which are the main components of sword bean, were condensed into other volatile flavor compounds, such as derivatives of furan, pyrazine, and pyrrole during roasting. Roasted and cryogenically ground (cryo-ground) sword beans showed higher functionality in terms of TFC, DPPH, and ABTS radical scavenging activities compared to those of coffee. Overall results showed that light roasting and cryogenic grinding are the most suitable processing conditions for enhancing the bioactivity of sword beans.

Green synthesis and investigation of antioxidant ability new pyrazines containing pyrrolo[2,1‐a]isoquinolines derivatives

AbstractIn this study, a new, easy and high yield procedure is investigated for the generation of pyrazine containing pyrrolo[2,1‐a]isoquinoline derivatives using multicomponent reaction of phthalaldehyde or its derivatives, primary amines, α‐haloalketones, electron deficient acetylenic compounds, ammonium acetate and KF/Clinoptilolite nanoparticles (KF/CP NPs) as catalyst in water at room temperature. The reactions of 2‐hydroxy phthalaldehyde, primary amines, α‐haloketones, electron deficient acetylenic compounds, and ammonium acetate in the presence of KF/CP NPs as catalyst in water at room temperature produce pyrazine derivatives in good yields. Also, in this work, antioxidant ability was studied for a number of prepared compounds employing the 2,2‐diphenyl‐1‐picrylhydrazyl (DPPH) radical scavenging and power of compounds for reducing of ferric ion experiments and evaluating results with synthetic antioxidants (TBHQ and BHT). Comfortable, simple, fast and fresh procedure is the advantages of this study.

Development of an antioxidant formula based on peanut by-products and effects on sensory properties and aroma stability of fortified peanut snacks during storage.

An antioxidant formula based on peanut skins and hulls was developed and characterized for total and single polyphenols, as well as antioxidant power, considering the contribution provided by each peanut by-product. Subsequently, it was evaluated for its effect on the sensory properties and aroma stability of peanut bars over a 100-day period. To this purpose, snacks fortified, or not, with the natural additive were experimentally produced. Peanut hulls contributed to a greater extent than skins with respect to boosting the content of bioactives and the antioxidnt activity of the antioxidant formula, which was marked by a phenol content of (approximately 807 mg gallic acid equivalents g-1 ) and a 2,2-diphenyl-1-picrylhydrazyl activity similar to that of butylated hydroxytoluene (85.96% and 89.30%, respectively). From a sensory perspective, the incorporation of the formulation in snacks caused only a slightly stronger perception of astringent and bitter notes. Pyrazines, phenol, furan and pyrrole derivatives defined the aroma of snacks, being more abundant in fortified than in conventional samples. Such volatiles faded over storage, with different trends in the examined products. For example, the sum of 2,5-dimethylpyrazine, 2-ethylpyrazine and 2,3-dimethylpyrazine was 9.49 and 8.87 ppm at day 15; 5.57 and 7.16 ppm at day 45; and 5.03 and 4.65 ppm at day 100, respectively, in fortified and conventional snacks. Hydroxymethylfurfural decreased constantly over storage in conventional samples and only after day 45 in fortified bars. Overall, the antioxidant formulation did not compromise the sensory desirability of peanut snacks and induced a preservative effect on their aroma, especially during the first 15 days of storage. © 2020 Society of Chemical Industry.

Volatile Organic Compounds From Lysobacter capsici AZ78 as Potential Candidates for Biological Control of Soilborne Plant Pathogens.

The genus Lysobacter includes several bacterial species which show potential for being used in biological control of plant diseases. It was shown recently that several Lysobacter type strains produce volatile organic compounds (VOCs) which controlled the growth of Phytophthora infestans in vitro when the bacteria were grown on a protein rich medium. In the present study, Lysobacter capsici AZ78 (AZ78) has been tested for its potential to produce VOCs that may contribute to the bioactivity against soilborne plant pathogens. To this end, split Petri dish assays of bacterial cultures have been combined with GC-MS measurements with the aim to reveal the identity of the VOCs which inhibit the growth of Pythium ultimum Rhizoctonia solani, and Sclerotinia minor. While AZ78 completely suppressed the growth of P. ultimum and S. minor, the growth of R. solani was still reduced significantly. The GC-MS analysis revealed 22 VOCs to be produced by AZ78, the majority of which were (putatively) identified as mono- and dialkylated methoxypyrazines. Based on additional cultivation and GC-MS experiments, 2,5-dimethylpyrazine, 2-ethyl-3-methoxypyrazine and 2-isopropyl-3-methoxypyrazine were selected as presumable bioactive compounds. Further bioassays employing indirect exposure to standard solutions (1–10 mg per Petri dish) of the synthetic compounds via the gas phase, revealed that each of these pyrazines was able to suppress the growth of the pathogens under investigation. The results of this study highlight the possible future implementation of pyrazine derivatives in the control of soilborne plant diseases and further support the biocontrol potential of L. capsici AZ78.

A computational strategy to understand structure-activity relationship of 1,3-disubstituted imidazole [1,5-α] pyrazine derivatives described as ATP competitive inhibitors of the IGF-1 receptor related to Ewing sarcoma

We followed a comprehensive computational strategy to understand and eventually predict the structure-activity relationship of thirty-three 1,3-disubstituted imidazole [1,5-α] pyrazine derivatives described as ATP competitive inhibitors of the IGF-1 receptor related to Ewing sarcoma. The quantitative structure-activity relationship model showed that the inhibitory potency is correlated with the molar volume, a steric descriptor and the net charge calculated value on atom C1 (q1) and N4 (q4) of the pharmacophore, all of them appearing to give a positive contribution to the inhibitory activity. According to experimental and calculated values, the most potent compound would be 3-[4-(azetidin-2-ylmethyl) cyclohexyl]-1-[3-(benzyloxy) phenyl] imidazo [1,5-α]pyrazin-8-amine (compound 23). Docking was used to guess important residues involved in the ATP-competitive inhibitory activity. It was validated by 200ns of molecular dynamics (MD) simulation using improved linear interaction energy (LIE) method. MD of previously preferred structures by docking shows that the most potent ligand could establish hydrogen bonds with the ATP-binding site of the receptor, and the Ser979 and Ser1059 residues contribute favourably to the binding stability of compound 23. MD simulation also gave arguments about the chemical structure of the compound 23 being able to fit in the ATP-binding pocket, expecting to remain stable into it during the entire simulation and allowing us to hint the significant contribution expected to be given by electrostatic and hydrophobic interactions to the ligand-receptor complex stability. This computational combined strategy here described could represent a useful and effective prime approach to guide the identification of tyrosine kinase inhibitors as new lead compounds.

Identification of a novel oxidation product from yellow fluorophore in the complex of apoPholasin and dehydrocoelenterazine

The complex of the recombinant fusion protein of apoPholasin and glutathione S-transferase (GST-apoPholasin) with non-fluorescent dehydrocoelenterazine (dCTZ) (GST-apoPholasin/dCTZ complex) shows yellow fluorescence at 539 nm by excitation at 430 nm. The GST-apoPholasin/dCTZ complex with a fluorophore (dCTZ*) has considerably weak luminescence activity, converting slowly to a blue fluorescence protein with the emission peak at 430 nm. The main oxidation products from dCTZ* for blue fluorescence were identified as coelenteramine (CTM) and an unreported pyrazine derivative, 3-benzyl-5-(4-hydroxyphenyl)pyrazin-2(1H)-one (CTO) that was confirmed by chemical synthesis.

Physicochemical profile of Os (III) complexes with pyrazine derivatives: From solution behavior to DNA binding studies and biological assay

New series of osmium(III) complexes with pyrazinamide (PZA) and its analogues (PTCA, PAOX) were synthesized. The physicochemical features in the solid phase have been identified and confirmed using elemental analysis, mass spectrometry, spectroscopic techniques (FT-IR, 1H NMR) and thermogravimetric analysis. Based on the studies we confirmed bidentate nature of selected pyrazine derivatives and proven involvement azomethine and amine nitrogen atoms in coordination of metal ion. In particular, complex (2) is more stable than (1) and (3), retaining thermal stability up to 120 °C. After one stage dehydration process, the simultaneous destruction of Os(III) complexes architecture was observed with immediate decomposition and elimination of pyrazine derivatives. The acid-base equilibria studies of newly synthesized Os(III) complexes were carried out by combined pH-metric-spectrophotometric and potentiometric titrations in the aqueous solution. Os(III) complexes exhibited rich redox chemistry as demonstrated by cyclic voltammetry. The cyclic voltammograms revealed a well-defined redox couples which correspond to reversible, single-electron OsIII → OsII reduction within ‐1.152 to ‐1.374 V vs Ag/AgCl and OsIII → OsIV oxidation within 0.460–0.831 V vs Ag/AgCl. The binding ability of bioactive ligand and their Os(III) complexes with Calf Thymus DNA (CT-DNA) were investigated by spectrophotometric titration. The observed hypsochromic and bathochromic shifts with simultaneous hyperchromic effect confirmed mixed mode of interaction with biological target. Biological activity of Os(III) complexes, i.e. antimicrobial, cytotoxic, haemolytic and photodynamic potential were studied.

Synthesis and Characterization of Pyrazine Derived Compounds as Potential Materials for Hole Transporting Layer (HTL)

Three simple compounds that have the potential as a hole transporting layer (HTL) based on pyrazine derivatives conjugated with electron donor groups in the form of triphenylamine have been successfully synthesized and characterized. The synthesis began with a substitution reaction at high temperatures between 4-bromoaniline and 4-iodoanisole to produce 4-bromo-N,N-bis(methoxyphenyl)-aniline, followed by substitution of bromo atoms with tributylstanum at low temperatures and inert atmosphere (N2) producing 4-methoxy-N-(4-(tributylstanyl)phenyl)aniline. The conjugation reaction was carried out through a Stille coupling reaction between 1,2-bis (4-bromophenyl)ethane-1,2-dione with 4-methoxy-N-(4-(tributylstanyl)phenyl) aniline at high temperatures with the aid of a Pd(PPh3)4 catalyst in an inert atmosphere (N2). The reaction was continued with the imination reaction with 3 compounds, i.e., 1,2-diaminobenzene, 3,3-diaminobenzidine and 2,3-diaminopiridin to produce three HTL compounds that were namely 4’,4”-(quinoxaline-2,3-diyl)bis (N,N-bis(4(methoxyphenyl)-[1,1’-biphenyl]-4-amine) (DNB), 4’,4’’’,4’’’’’,4’’’’’’’-([6,6’-biquinoxaline]-2,2’,3,3’-tetrayl) tetrakis(N,N-bis(4-methoxyphenyl)- [1,1’-biphenyl] -4-amine) (bDNB), and 4’,4’’’-(pyrido[2,3-b]pyrazine-2,3-diyl)bis(N,N-bis (4-methoxyphenyl)-[1,1’-biphenyl]-4-amine) (DNP). The optical and electrochemical properties of DNB, bDNB, and DNP were analyzed by UV-Vis and Differential Pulse Voltammetry (DPV). The optical and electrochemical properties show the energy levels of the HOMO and LUMO of the three compounds. Hence their potential can be estimated as HTL compounds. The three compounds show λmax of 348 nm, 356 nm, and 350 nm for DNB, bDNB, and DNP. Based on DPV results, the HOMO values for DNB, bDNB, and DNP are -5.03 eV, -5.02 eV, and -4.98 eV and LUMO values of -2.46 eV, -2.76 eV and -2.87 eV, respectively. The three compounds' thermal properties were analyzed using TGA, with the results showing that the three compounds had good thermal resistance with a decomposition point above 400°C. Based on optical, electrochemical, and thermal analysis, DNB and bDNB have almost the same properties. Thus, it is expected that the three compounds have the potential as HTL material, with DNB and bDNB better than DNP.

A co-crystal strategy for the solidification of liquid pyrazine derivatives: X-ray structures and Hirshfeld surface analyses

Here we described a co-crystal strategy for the solidification of liquid 2,3-dimethylpyrazine (2,3-DMP), 2,5-dimethylpyrazine (2,5-DMP), 2,6-dimethylpyrazine (2,6-DMP) with the poly-substituted salicylic acids [3,5,6-trichlorosalicylic acid (TCSA) and 3,5-dinitrosalicylic acid (DNSA)] under identical conditions. Those newly grown co-crystals (2,3-DMP:TCSA = 1:1 for 1; 2,5-DMP:TCSA = 1:2 for 2; 2,6-DMP:DNSA = 1:1 for 3) were characterized by single-crystal X-ray diffraction. The structure determination shows that strong O-H⋯N hydrogen bonds play an important role in connection of pyrazine derivatives and poly-substituted salicylic acids. Moreover, aromatic cycle stacking interactions play a crucial role in the 3D supramolecular network. Hirshfeld surfaces and fingerprint plots of the reported co-crystals were analyzed, which showed that O-H⋯N, C-H⋯O, H⋯H, H⋯Cl and aromatic cycle stacking intermolecular interactions are the main stabilizing factors of the co-crystal structures. The melting points studies showed that the co-crystal strategy is effective for solidification of liquid pyrazine derivatives.

Biopreservation of tomatoes using fermented media by lactic acid bacteria

Post-harvest spoilage fungi in tomatoes represent an economic loss for industry and consumers. There is currently an increasing demand for novel applications of bio-preservatives as replacers of chemical additives and pesticides in food. In this study, nine lactic acid bacteria strains isolated from tomato and sourdough were screened for antifungal activity in vitro against 33 fungal strains and used as bio-preservatives of tomato inoculated with Penicillium expansum and Aspergillus flavus. The identification of the compounds potentially responsible for the antifungal activity, such as organic acids, phenolic acids and volatile organic compounds (VOCs), were identified and quantified. Several cell-free supernatants (CFS) showed in vitro antifungal activity against toxigenic fungi. The highest antifungal activity was observed in the CFS of Lactobacillus plantarum TR7 and L. plantarum TR71, these showed a range of MFC values of 6.3–100 g/L. Antifungal compounds were identified in CFS as organic acids, phenolic acids and VOCs. Lactic acid, acetic acid, phenyllactic acid and pyrazine derivatives can be related for the antifungal activity. Bio-preservation of tomato with the CFS fermented by L. plantarum TR7 and L. plantarum TR71 decreased the microbial count by 1.98–3.89 log10 spores/g in comparison to the treatment with medium non-fermented.

Oxidative Ring‐Opening of 1H‐Pyrazol‐5‐amines and Its Application in Constructing Pyrazolo–Pyrrolo–Pyrazine Scaffolds by Domino Cyclization

Herein, an oxidative ring‐opening of 1H‐pyrazol‐5‐amines to form 3‐diazenylacrylonitrile derivatives under mild and transition‐metal‐free conditions is described. In addition, the nucleophilic addition of deprotonated 1H‐pyrrole‐2‐carbaldehydes to the vinyl moiety of the yielded 3‐diazenylacrylonitriles could trigger domino cyclization to afford the 3H‐pyrazolo[3,4‐e]pyrrolo[1,2‐a]pyrazine derivatives. Computational studies suggest that the oxidation of 1H‐pyrazol‐5‐amines in the presence of PhIO is through the formation of a hydroxylamine intermediate followed by elimination of H2O to result in the ring‐opening product. The detailed domino cyclization pathway leading to the pyrazolo–pyrrolo–pyrazine scaffolds is revealed.