Pyrazine Research Articles

Spin-Resolved Band Structure of Hoffman Clathrate [Fe(pz)2Pt(CN)4] as an Essential Tool to Predict Optical Spectra of Metal–Organic Frameworks

Paramount spin-crossover properties of the 3D-Hoffman metalorganic framework (MOF) [Fe(pz)2Pt(CN)4] are generally described on the basis of the ligand field theory, which provides adequate insight into theoretical and simulation analysis of spintronic complexes. However, the ligand field approximation does not take into account the 3D periodicity of the actual complex lattice and surface effects and therefore cannot predict a full-scale periodic structure without utilizing more advanced methods. Therefore, in this paper, the electronic properties of the exemplar MOF were analyzed from the band structure perspective in low-spin (LS) and high-spin (HS) states. The density-of-states spectra determined for both spin-up and spin-down electrons of Fe d6 orbitals indicate spin-orbital splitting and delocalization for HS due to spin polarization in the iron atom ligand field. Presence of the surface states in the real crystal causes a red shift of the metal-metal charge transfer (MMCT) and metal-ligand charge transfer (MLCT) peaks for both HS and LS states. The addition of residual water molecules and disorder among the pyrazine rings reveal additional influences on the positions of the pyrazine band and, therefore, on the absorption spectra of the crystal. The results show a magnification of the peak correlated with the MLCT in the HS state and a significant red shift of the LS characteristic absorption band. The presented approach involving band structure analysis delivers a more complete image of the electronic properties of the [Fe(pz)2Pt(CN)4] crystalline network and can be a landmark for insightful studies of other MOFs.

Pyrazine-Functionalized Donor-Acceptor Covalent Organic Frameworks for Enhanced Photocatalytic H2 Evolution with High Proton Transport.

The well-defined 2D or 3D structure of covalent organic frameworks (COFs) makes it have great potential in photoelectric conversion and ions conduction fields. Herein, a new donor-accepter (D-A) COF material, named PyPz-COF, constructed from electron donor 4,4',4″,4'″-(pyrene-1,3,6,8-tetrayl)tetraaniline and electron accepter 4,4'-(pyrazine-2,5-diyl)dibenzaldehyde with an ordered and stable π-conjugated structure is reported. Interestingly, the introduction of pyrazine ring endows the PyPz-COF a distinct optical, electrochemical, charge-transfer properties, and also brings plentiful CN groups that enrich the proton by hydrogen bonds to enhance the photocatalysis performance. Thus, PyPz-COF exhibits a significantly improved photocatalytic hydrogen generation performance up to 7542µmol g-1 h-1 with Pt as cocatalyst, also in clear contrast to that of PyTp-COF without pyrazine introduction (1714µmol g-1 h-1 ). Moreover, the abundant nitrogen sites of the pyrazine ring and the well-defined 1D nanochannels enable the as-prepared COFs to immobilize H3 PO4 proton carriers in COFs through hydrogen bond confinement. The resulting material has an impressive proton conduction up to 8.10 × 10-2 S cm-1 at 353 K, 98% RH. This work will inspire the design and synthesis of COF-based materials with both efficient photocatalysis and proton conduction performance in the future.

L-Serine is the Direct Precursor for the Pyrazine Ring Construction in the Biosynthesis of 3-Isobutyl-2-Methoxypyrazine in Bell Pepper Fruits (Capsicum annuum L.).

3-Isobutyl-2-methoxypyrazine (IBMP) is an extremely potent odorant and responsible for the specific aroma of many fruits and vegetables. Especially bell pepper contains high levels of IBMP, which is the character impact compound of its typical aroma. However, since the discovery of methoxypyrazines in plants in the 1960s the biosynthesis of their pyrazine ring motif remained so far unknown. Therefore, the biosynthetic pathway to IBMP was investigated by feeding experiments with stable-isotope labeled precursors. For the first time it could be shown that l-serine plays a key role in the pyrazine ring construction of 3-alkyl-2-methoxypyrazines (MPs). Based on HS-SPME-GCxGC-TOF-MS analysis, it is shown that the biosynthetic pathway to IBMP is closely linked to photorespiratory derived l-serine.

Identification of novel inhibitors against hantaviruses through 2D fingerprinting and molecular modeling approaches.

With the immensely growing outbreaks of hantavirus with still no effective treatment available, there is an urgent need of exploring new computational approaches which will target potential virulent proteins that will eventually reduce its growth. In this study, an envelope glycoprotein, Gn, was targeted. The glycoproteins, which are the sole targets of neutralizing antibodies, drive virus entry via receptor-mediated endocytosis and endosomal membrane fusion. Inhibitors are herein proposed to negate its action mechanism. On the basis of the scaffolds of favipiravir, a FDA compound already used against hantavirus, a library was designed using a 2D fingerprinting approach. Upon molecular docking analysis, the top four docked compounds-(1) favipiravir (-4.5 kcal/mol), (2) N-hydroxy-3-oxo-3, 4-dihydropyrazine-2-carboxamide (-4.7 kcal/mol), (3) N, 5, 6-trimethyl-2-oxo-1H-pyrazine-3-carboxamide (-4.5 kcal/mol), and (4) 3-propyl-1H-pyrazin-2-one (-3.8)-were prioritized on the basis of the lowest binding energies score. Through molecular docking, the best-categorized compound was subjected to molecular dynamics simulation for a 100-ns time span. Molecular dynamics sheds light on each ligand behavior within the active site. Among the four complexes, only favipiravir and 6320122 compound were found to be stable inside the pocket. This is due to the presence of common rings, pyrazine and carboxamide ring, which make a significant interaction with active key residues Furthermore, the MMPB/GBSA binding free energy analysis calculated for all complexes supported the dynamics results by calculating the most stable values for favipiravir complex (-9.9933 and -8.6951 kcal/mol) and for 6320122 compound complex (-13.8675 and -9.3439 kcal/mol), which demonstrated that the selected compounds have a proper binding affinity with the targeted proteins. The hydrogen bond analysis similarly revealed a strong bonding interaction. The results yielded a strong interaction between the enzyme and the inhibitor throughout the simulation; thus, the inhibitor has the potential to become a lead compound and could be subjected to experimental evaluation to unveil their blockage ability.

X-ray studies of three 3,6-bis(pyridin-2-yl)-1,2,4,5-tetrazine cocrystals: an unexpected molecular conformation stabilized by hydrogen bonds

The results of the X-ray structure analysis of three novel 3,6-bis(pyridin-2-yl)-1,2,4,5-tetrazine cocrystals are presented. These are 3,6-bis(pyridin-2-yl)-1,2,4,5-tetrazine-2,4,6-tribromophenol (1/2), C12H8N6·2C6H3Br3O, 3,6-bis(pyridin-2-yl)-1,2,4,5-tetrazine-isonicotinic acid N-oxide (1/2), C12H8N6·2C6H5NO3, and 3,6-bis(pyridin-2-yl)-1,2,4,5-tetrazine-4-nitrobenzenesulfonamide (1/1), C12H8N6·C6H6N2O4S. Special attention is paid to a conformational analysis of the title tetrazine molecule in known crystal structures. Quantum chemistry methods are used to compare the energetic parameters of the investigated conformations. A structural analysis of the hydrogen and halogen bonds with acceptor aromatic tetrazine and pyrazine rings is conducted in order to elucidate factors responsible for conformational stability.

Nature of the dative Nitrogen-Coinage metal bond in molecular Motors. Evaluation of NHC-M pyrazine bond (M = Cu, Ag, Au) from relativistic DFT

The use of different N-heterocyclic carbene (NHC) coordinated to coinage metals are useful caps for generating mechanical bonds towards donor-nitrogen fragments, leading to the characterization of efficient molecular motors. Here, we account for the nature of the formation of mechanical bonds on [(NHC-M)2pyz]2+ (M = Cu, Ag, Au; pyz = pyrazine) complexes. The NHC-M pyrazine interaction is of main electrostatic character given by the Lewis acidic σ-hole characteristics of the NHC-M caps, and the Lewis basic features of the aromatic pyrazine ring, accounting for the 69.9 %, 71.8 %, and 68.8 %, for Cu, Ag, and Au species, respectively. The rotational barrier is calculated at 10.2, 8.6, and 6.0 kcal mol−1, respectively, which is given by the variation of the NHC-M pyrazine interaction, and structural arrangements, accounting for 54.0/46.0 %, 59.3/40.7 %, and, 79.8/20.2 %, for Cu, Ag, and Au, respectively. Hence, the rotational barrier for the gold counterpart is less affected by structural factors. Relativistic effects on the N-coinage metal bond interaction are crucial for the account of the experimentally observed rotational barrier. Thus, the theoretical evaluation of mechanical bonds allows to gain further insights into the fundamental nature of the interaction and how structural factors affect the formation of molecular motors relevant to guide design and synthetic efforts.

From isostructural to hetero-structural one-dimensional coordination polymers adjusted by changing the ligand substituent group from pyrazine to furan

A new ligand, 4-(4-carboxyphenyl)-6-(pyrazin-2-yl)picolinic acid (H2L1), was used to construct four isostructural one-dimensional (1 D) zig-zag chain coordination polymers ([M(L1)(H2O)2]·3H2O, M = Mn (1), Co (2), Cd (3) and Zn (4)). Moreover, when changing the ligand substituent group from pyrazine ring to furan ring, another new ligand, 4-(4-carboxyphenyl)-6-(furan-2-yl)picolinic acid (H2L2), was synthesized. Based on H2L2, different structural 1 D coordination polymers, ([Mn(L2)(H2O)2] (5) and [Ni(L2)(H2O)2]·H2O (6)), have been obtained under the same solvothermal conditions as for the syntheses of isostructural 1–4. Interestingly, only through changing the ligand substituent group, the 1 D isostructural zig-zag chain (1–4) was adjusted to a 1 D molecular box chain (5) and 1 D linear chain (6), which should be ascribed to ligand substituent group effects. The various 1 D chain structures originate from the types of ligand substituent group: the substituent group with a pyrazine ring only yields isostructural coordination polymers 1–4, whereas the substituent group with a furan ring can construct different structural coordination polymers, such as a 1 D molecular box chain (5) or a 1 D linear chain (6). The photoluminescent properties of all coordination polymers were also examined.

Modeling of the formation of triple complexes of the essential trace element iron with riboflavin and essential amino acids

In this work, we simulated the process of formation of triple complexes of the essential trace element iron with riboflavin and essential amino acids. The simulation was carried out in the QChem software using the IQmol molecular editor. To begin with, the modeling of the molecules of essential amino acids was carried out: L-valine, L-leucine, L-isoleucine, Lmethionine, L-threonine, L-lysine, L-phenylalanine and L-tryptophan. Modeling was carried out by the interaction of the iron atom with various pairs of nitrogen heteroatom and enol oxygen of riboflavin, as well as with the carboxyl group and α-amino group of the amino acid. As a result, it was found that the interaction of the trace element iron with riboflavin and essential amino acids is energetically favorable (∆E > 2575 kcal/mol) and chemically stable (0.075 ≤ η ≤ 0.138 eV). Based on the data obtained, the most probable configuration of the molecular complex was determined - interaction with riboflavin through N5 in the pyrazine ring and enol oxygen attached to the C4 atom in the pyrimidine ring of riboflavin. The molecular system that has the highest difference in total energy (∆E = 2577.501) and chemical hardness (η = 0.138 eV), and therefore the most energetically favorable and chemically stable, is the copper valinatoriboflavinate molecular complex, in which the interaction of iron with riboflavin occurs through N5 in the pyrazine ring and enol oxygen attached to the C4 atom in the pyrimidine ring riboflavin.

Nickel (II) coordination polymer using pyrazine linkers and phthalate counter-anion: Synthesis, crystal structure, Hirshfeld surface and voids analysis

Herein, a new Ni(II) carboxylate polymer, [Ni(Pyr).4H 2 O]Phth , is synthesized by the reaction of NiSO 4 .7H 2 O with equimolar amounts of phthalic acid (PhthH 2 ) as the counter-anion and pyrazine (Pyr) as an ancillary ligand in aqueous media. The crystal structure of [Ni(Pyr).4H 2 O]Phth is investigated by single crystal X-rays diffraction analysis, which inferred the ionic nature of the complex. In cation, the Ni-center is coordinated by two pyrazine rings and four water molecules to form an octahedral coordination geometry. The crystal structure exists as a one-dimensional polymeric structure. The crystal packing is stabilized by OH O and CH O bonding. The non-covalent interactions are investigated by Hirshfeld surface analysis. The enrichment ratio delivers the tendency of the interaction of the pair of chemical moieties, which are involved in the packing of crystals. Moreover, void analysis is executed to look at the packing efficiency, which helps in predicting the mechanical response of the compound.

Synthesis of New Derivatives of Leaf-Eating Ant Toxic Gland Pheromone Compounds and Investigation of their Biological Properties

‌Background: The anti-mycobacterial characteristics of 2-pyrazinoic acid esters have been discovered through recent research. Research has demonstrated that the pyrazine ring and the alkyl part of these compounds interact with the enzyme phytynetase, which in turn inhibits the interaction between NADPH and mycobacterial fatty acids synthase, the enzyme responsible for synthesizing the fatty acids required for the cell wall of mycobacteria. Materials and Methods: Targeted pyrazinoic acid molecules have been synthesized, their structure verified by spectroscopic data, and their anti-mycobacterial activity against Mycobacterium TB H37Rv at a dose of 10 micrograms per milliliter assessed in order to test this theory. Significant anti-mycobacterial capabilities were shown by several compounds, including 3c, 3J, and 3M, which inhibited mycobacterial growth by 45.7%, 45.4%, and 51%, respectively. Findings: The results showed that the compounds exhibited little toxicity and did not inhibit macrophage cell proliferation. Pyrazinamide had significant antibacterial and antifungal activity, despite its lack of fatal action against non-tubercular mycobacteria and both Gram-positive and Gram-negative bacteria. Compound 3B, for example, exhibited excellent antibacterial properties against Gram-positive bacteria, such as S. aureus, with a minimum inhibitory concentration (MIC) of 125 micrograms per milliliter. Conversely, the compounds showed equally potent antibacterial properties against Gram-negative bacteria. Interestingly, compared to Gram-positive bacteria, the ester produced from maltol exhibited greater antibacterial efficacy against Gram-negative bacteria. Compounds synthesized with biodegradable groups also exhibited time-dependent toxicity against K562 leukemia cancer cells in MTT measurements, with compounds 3e and 3J displaying IC50 values of 25 micromolars. Conclusion: After synthesizing pyrazinoic acid monoterpene esters, spectral data was used to confirm their structures. When their biological characteristics were assessed, toxicity studies against K562 leukemia cells produced encouraging results. Through the use of Thio Ester-mediated activation of 2-pyrazinoic acid by 2, 2-dibenzothiazole disulfide and triphenylphosphine, 6-aminopenicillanic acid (6-APA) was coupled with pyrazinoic acid.

Copper(ii) and silver(i) complexes with dimethyl 6-(pyrazine-2-yl)pyridine-3,4-dicarboxylate (py-2pz): the influence of the metal ion on the antimicrobial potential of the complex.

Dimethyl 6-(pyrazine-2-yl)pyridine-3,4-dicarboxylate (py-2pz) was used as a ligand for the synthesis of new copper(ii) and silver(i) complexes, [CuCl2(py-2pz)]2 (1), [Cu(CF3SO3)(H2O)(py-2pz)2]CF3SO3·2H2O (2), [Ag(py-2pz)2]PF6 (3) and {[Ag(NO3)(py-2pz)]·0.5H2O} n (4). The complexes were characterized by spectroscopic and electrochemical methods, while their structures were determined by single crystal X-ray diffraction analysis. The X-ray analysis revealed the bidentate coordination mode of py-2pz to the corresponding metal ion via its pyridine and pyrazine nitrogen atoms in all complexes, while in polynuclear complex 4, the heterocyclic pyrazine ring of one py-2pz additionally behaves as a bridging ligand between two Ag(i) ions. DFT calculations were performed to elucidate the structures of the investigated complexes in solution. The antimicrobial potential of the complexes 1-4 was evaluated against two bacterial (Pseudomonas aeruginosa and Staphylococcus aureus) and two Candida (C. albicans and C. parapsilosis) species. Silver(i) complexes 3 and 4 have shown good antibacterial and antifungal properties with minimal inhibitory concentration (MIC) values ranging from 4.9 to 39.0 μM (3.9-31.2 μg mL-1). All complexes inhibited the filamentation of C. albicans and hyphae formation, while silver(i) complexes 3 and 4 had also the ability to inhibit the biofilm formation process of this fungus. The binding affinity of the complexes 1-4 with calf thymus DNA (ct-DNA) and bovine serum albumin (BSA) was studied by fluorescence emission spectroscopy to clarify the mode of their antimicrobial activity. Catechol oxidase biomimetic catalytic activity of copper(ii) complexes 1 and 2 was additionally investigated by using 3,5-di-tert-butylcatechol (3,5-DTBC) and o-aminophenol (OAP) as substrates.

Combined Experimental and Theoretical Investigation into the Photophysical Properties of Halogenated Coelenteramide Analogs.

Marine Coelenterazine is one of the most well-known chemi-/bioluminescent systems, and in which reaction the chemi-/bioluminophore (Coelenteramide) is generated and chemiexcited to singlet excited states (leading to light emission). Recent studies have shown that the bromination of compounds associated with the marine Coelenterazine system can provide them with new properties, such as anticancer activity and enhanced emission. Given this, our objective is to characterize the photophysical properties of a previously reported brominated Coelenteramide analog, by employing a combined experimental and theoretical approach. To better analyze the potential halogen effect, we have also synthesized and characterized, for the first time, two new fluorinated and chlorinated Coelenteramide analogs. These compounds show similar emission spectra in aqueous solution, but with different fluorescence quantum yields, in a trend that can be correlated with the heavy-atom effect (F > Cl > Br). A blue shift in emission in other solvents is also verified with the F−Cl−Br trend. More relevantly, the fluorescence quantum yield of the brominated analog is particularly sensitive to changes in solvent, which indicates that this compound has potential use as a microenvironment fluorescence probe. Theoretical calculations indicate that the observed excited state transitions result from local excitations involving the pyrazine ring. The obtained information should be useful for the further exploration of halogenated Coelenteramides and their luminescent properties.

Near-Zero Thermal Expansion and High Heat-Resistance Polyimide Films Based on a Symmetric and Rigid Pyrazine Structure

Regarding the applications of polyimide (PI) films in emerging flexible devices and precision apparatus, their low coefficient of thermal expansion (CTE), especially near-zero expansion, is an urgent requirement for weakening the internal stress between the organic/inorganic layers. Other properties of PI films including the high heat-resistance and superior toughness are also demanded in actual scenarios. Herein, a set of PI films was developed by copolymerization of 2,5-bis(4-aminophenyl)pyrazine (PRZ) into a pyromellitic dianhydride (PMDA)/4,4′-oxydianiline (ODA) system. The monocrystal analysis of the PRZ monomer reveals its rigid, symmetric, and nearly coplanar steric structure. Thanks to the synergy and balance of flexible ODA and rigid PRZ units in PI chains, the near-zero expansion, high heat-resistance, and optimal mechanical properties of the PI films are simultaneously achieved. Particularly, the PI film with ODA/PRZ = 4.5/5.5 presents a near-zero CTE of −0.41 ppm/K, high glass transition temperature (Tg) of around 417 °C, superior fracture strength of 191 MPa, and initial modulus of 3.83 GPa. Interestingly, via adjusting the ODA/PRZ ratios, the precise control of CTE values can be realized, enabling the thermal expansion matching of PI films on broad types of device substrates, e.g., Cu (15–17 ppm/K) and Si (3–5 ppm/K).

SYNTHEZIS AND STRUCTURAL INVESTIGATION OF bis-(PYRAZIN 2-CARBOXYLATE)-Ni(II)-DIHIDRATE

A new Ni (II) C pyrazine 2-carboxylic acid complex was synthesized. Single crystals were obtained for X-ray diffraction analysis and the crystal and molecular structures of the new complex were deciphered. The crystallographic parameters of complex compounds are as follows: Molecular formula is C10H10N4NiO6, Molecular weight is 340.91 k.v.; temperature during measurement is 100.0 (2) K; Absorption frequency is MoKα = 0.71073E, Syngonia – Monoclinic; space group is P21 /c, Crystal lattice parameters are: a = 5.2136Å, b = 11.10073Å, c = 10.15267Å; β = 100.14620C, volume of the crystal lattice is V = 578.395Å3, number of molecules in the crystal lattice is Z = 2, density is d = 1,956 g / cm3, absorption coefficient is 1,715 mm-1, dimensions of the single crystal are 0.20x0.18x0,15 mm3; range of teta is 3.670–30.6100C; The boundaries of the hkl planes in the crystal section are h = -7+7 k = -15 +15.l = -14+14 the total number of collected reflexes is 8546, the number of independent reflexes is 1727, the boundary of the transitions is 0.761 and 0.707. Total Rfactor = 0.0240. It has been found that the central Ni(II) atom is coordinated by one oxygen atom of the carboxyl group and a donor nitrogen atom of the pyrazine ring, forming five-membered stable bonds. Two water molecules are coordinated by the Ni(II) atom and complete the coordination number of the metal to six. The Ni–O bond distance is 2.0874 Å, the Ni-N bond distance is 2.0864 Å. The second oxygen atom is not coordinated by the Ni(II) atom and forms a strong hydrogen bond with coordinated water molecules

Cytotoxic monoaryl furazanopyrazines with microtubule destabilizing activity in the sea urchin embryo model

Biological activity of monoaryl furazanopyrazines (FPs), known as high-energy molecules, is scarcely explored. A series of monoaryl FPs was synthesized by condensation of arylglyoxals with diaminofurazane. The targeted compounds at low micromolar concentrations inhibited growth of human cancer cells in NCI60 screen. Further evaluation using a sea urchin embryo model revealed that antiproliferative activity of monoaryl FPs could be associated with targeting tubulin and microtubule destabilization, systemic (nonspecific) toxicity, or both. Introduction of hydroxy group into pyrazine ring of monoaryl FPs yielded inactive molecules.

Synthesis, Characterization and Molecular Docking Studies of Novel Pteridine Derivatives

Pteridines are a group of heterocyclic compounds which contain nitrogen as a major heteroatom and it was aromatic compounds that are attached to the pyrazine and pyrimidine ring family. Pteridine derivatives have focused on a specific place in the medicinal chemistry field. The Pteridine ring is present in several natural compounds such as Pterin, Hemiptera (erythropoietin), Biopterin, Neopterin, Xanthopterin, iso-xanthopterin, etc., which include a few heterocyclic compounds like pyrimidine, pyrazine rings. Some vitamins like folic acid and riboflavin and drugs like methotrexate and triamterene. A pteridine is formed by a condensation process. A pteridine is frequently produced using costly and dangerous chemicals. In order to reduce the cost and consumption of hazardous chemicals, novel pteridine compounds were made by mixing a catalyst with a solvent, primary amines, and phenols. Currently, the primary issue limiting a medicine's ability to effectively treat a disease includes the development of resistance. In this article, we will utilise docking studies to provide a thorough explanation of the synthesis of pteridine derivatives and their antioxidant capabilities.

Computational Evaluation of Polycyclic Bis-Oxadiazolo-Pyrazine Backbone in Designing Potential Energetic Materials

4H,8H-bis[1,2,5]oxadiazolo[3,4-b:3',4'-e]pyrazine (bis-oxadiazolo-pyrazine) represents a versatile CHNO backbone for the design of energetic materials. In this paper, we report a comprehensive computational study using density functional theory to improve detonation properties of this CHNO backbone by introducing pyrazine rings, nitro groups, and N-oxide functionalities. The heat of formation, oxygen balance, density, and detonation properties of a series of furazan-pyrazine fused ring derivatives are computed. Their sensitivity and stability has been correlated with bandgap (ΔELUMO-HOMO), maximum heat of detonation (Q), and impact energy (h50). Introduction of –NO2 and N–oxide on the parent furazan-pyrazine fused ring derivatives is favorable for improving the heat of formation, oxygen balance and density. The heat of formation varies between 464.46 and 1043.57 kJ/mol, and the densities range from 1.75 to 2.01 g/cm3. The positive heat of formation and high densities achieved good detonation velocities (6.74 to 9.61 km/s) and pressures (19.96–43.65 GPa). Among the bis-oxadiazolo-pyrazine derivatives, P5, P6, Q5, Q6, R4, R5, and R6 are fascinating due to their high detonation performances, have calculated detonation velocities and pressures above 9.30 km/s and 40.0 GPa, respectively. Some furazan-pyrazine fused ring derivatives reveal good performance parameters with reasonable stability, confirming them as potential energetic compounds relative to RDX and HMX.

Metabolites of endophytic fungus Nigrospora sphaerica S5 from Myoporum bontioides

The endophytic fungus Nigrospora sphaerica S5 derived from the semi-mangrove plant Myoporum bontioides was fermented. Its metabolites were purified by column chromatography. Nine compounds were obtained and identified as terezine P(1), 3-(1-hydroxyethyl)-4-methyl dihydrofuran-2(3H)-one(2), methylhydroheptelidate(3), hydroheptelidic acid(4), 5, 7-dimethoxy-4, 6-dimethylphthalide(5),(3R,4S)-(-)-4-hydroxymellein(6), pestalopyrone(7), indole-3-formaldehyde(8) and p-hydroxybenzaldehyde(9) by spectroscopic techniques. Terezine P(1) was a new alkaloid belonging to the terezine class with a pyrazine ring. Compounds 2-7 were lactones, of which 3 and 4 belonged to sesquiterpenes. Compounds 8 and 9 were indole alkaloids and phenols, respectively. Compounds 3-6 were purified from Nigrospora sp. for the first time. These compounds showed different degrees of antibacterial activity against Staphylococcus aureus, Escherichia coli of O6 serotype and E. coli of O78 serotype.

Thiolumazines as Heavy-Atom-Free Photosensitizers for Applications in Daylight Photodynamic Therapy: Insights from Ultrafast Excited-State Dynamics.

Finding appropriate photosensitizers (PSs) for daylight photodynamic therapy (dPDT) applications is extremely challenging, even though heavy-atom-free photosensitizers (HAFPSs) such as thiocarbonyl-modified nucleobases have shown a ray of hope. Few attempts have been made to find alternative natural products for dPDT applications. Pteridine heterocycles consisting of a pyrazine ring and a pyrimidine ring, such as lumazine, which exhibit many structural similarities to the alloxazine ring of the flavin molecule, could be an option for HAFPSs. The photophysical and quantum mechanical studies of the thio-modified lumazines revealed that sequential thiomodifications in lumazine result in a bathochromic shift. Additionally, higher tissue penetration depths were observed for thiolumazines. The fluorescence quenching in the case of thiomodified lumazines was explained using triplet state formation, whereas the contribution from the photoinduced electron transfer process cannot be ignored. It was also noticed that a strong one-photon absorption influenced the two-photon absorption (TPA) process, leading to a self-focusing effect in the visible spectral region. The higher tissue penetration and larger TPA cross section are the hallmark characteristics of the thiolumazines to be considered as potential HAFPSs for dPDT applications.

Proteomic and Functional Analysis of the Effects of Quinoxaline Derivatives on Entamoeba histolytica.

Quinoxalines are heterocyclic compounds that contain a benzene ring and a pyrazine ring. The oxidation of both nitrogen of the pyrazine ring results in quinoxaline derivatives (QdNO), which exhibit a variety of biological properties, including antiparasitic activity. However, its activity against Entamoeba histolytica, the protozoan that causes human amebiasis, is poorly understood. Recently, our group reported that various QdNOs produce morphological changes in E. histolytica trophozoites, increase reactive oxygen species, and inhibit thioredoxin reductase activity. Notably, T-001 and T-017 derivatives were among the QdNOs with the best activity. In order to contribute to the characterization of the antiamebic effect of QdNOs, in this work we analyzed the proteomic profile of E. histolytica trophozoites treated with the QdNOs T-001 and T-017, and the results were correlated with functional assays. A total number of 163 deregulated proteins were found in trophozoites treated with T-001, and 131 in those treated with T-017. A set of 21 overexpressed and 24 under-expressed proteins was identified, which were mainly related to cytoskeleton and intracellular traffic, nucleic acid transcription, translation and binding, and redox homeostasis. Furthermore, T-001 and T-017 modified the virulence of trophozoites, since they altered their erythrophagocytosis, migration, adhesion and cytolytic capacity. Our results show that in addition to alter reactive oxygen species, and thioredoxin reductase activity, T-001 and T-017 affect essential functions related to the actin cytoskeleton, which eventually affects E. histolytica virulence and survival.