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Sample records for pyridine pyrrole indole

  1. Pyrrole-pyridine and pyrrole-naphthyridine hosts for anion recognition.

    PubMed

    García, M Angeles; Farrán, M Angeles; María, Dolores Santa; Claramunt, Rosa M; Torralba, M Carmen; Torres, M Rosario; Jaime, Carlos; Elguero, José

    2015-05-27

    The association constants of the complexes formed by two hosts containing pyrrole, amide and azine (pyridine and 1,8-naphthyridine) groups and six guests, all monoanions (Cl-, CH3CO2-, NO3-, H2PO4-, BF4-, PF6-), have been determined using NMR titrations. The X-ray crystal structure of the host N2,N5-bis(6-methylpyridin-2-yl)-3,4-diphenyl-1H-pyrrole- 2,5-dicarboxamide (1) has been solved (P21/c monoclinic space group). B3LYP/6-31G(d,p) and calculations were carried out in an attempt to rationalize the trends observed in the experimental association constants.

  2. Pyrrole and indole alkaloids from an endophytic Fusarium incarnatum (HKI00504) isolated from the mangrove plant Aegiceras corniculatum.

    PubMed

    Li, Li-Ya; Ding, Yi; Groth, Ingrid; Menzel, Klaus-Dieter; Peschel, Gundela; Voigt, Kerstin; Deng, Zi-Wei; Sattler, Isabel; Lin, Wen-Han

    2008-01-01

    Two new pyrrole alkaloids, N-[4-(2-formyl-5-hydroxymethyl-pyrrol-1-yl)-butyl]-acetamide (1) and N-[5-(2-formyl-5-hydroxymethyl-pyrrol-1-yl)-pentyl]-acetamide (2), and a new indole derivative (3aR,8aR)-3a-acetoxyl-1,2,3,3a,8,8a-hexahydropyrrolo-[2,3-b]indol (3) were isolated, together with ( - )-3a-hydroxyfuroindoline, (3aR,8aS)-1-acetyl-1,3,3a,8,8a-hexahydropyrrolo-[2,3-b]indol-3a-ol, and N-acetyltryptamine A, from an endophytic ascomycetous fungus, Fusarium incarnatum (HKI00504), which was isolated from the mangrove plant Aegiceras corniculatum. The structures of compounds 1-3 were determined on the basis of extensive spectroscopic data analyses.

  3. Highly enantioselective synthesis of beta-heteroaryl-substituted dihydrochalcones through Friedel-Crafts alkylation of indoles and pyrrole.

    PubMed

    Wang, Wentao; Liu, Xiaohua; Cao, Weidi; Wang, Jun; Lin, Lili; Feng, Xiaoming

    2010-02-01

    A highly enantioselective Friedel-Crafts (F-C) alkylation of indoles and pyrrole with chalcone derivatives catalyzed by a chiral N,N'-dioxide-Sc(OTf)(3) complex has been developed that tolerates a wide range of substrates. The reaction proceeds in moderate to excellent yields and high enantioselectivities (85-92 % enantiomeric excess) using 2 mol % (for indole) or 0.5 mol % (for pyrrole) catalyst loading, which showed the potential value of the catalyst system. Meanwhile, a strong positive nonlinear effect was observed. On the basis of the experimental results and previous reports, a possible working model is proposed to explain the origin of the activation and asymmetric induction.

  4. Direct detection of pyridine formation by the reaction of CH (CD) with pyrrole: a ring expansion reaction

    SciTech Connect

    Soorkia, Satchin; Taatjes, Craig A.; Osborn, David L.; Selby, Talitha M.; Trevitt, Adam J.; Wilson, Kevin R.; Leone, Stephen R.

    2010-03-16

    The reaction of the ground state methylidyne radical CH (X2Pi) with pyrrole (C4H5N) has been studied in a slow flow tube reactor using Multiplexed Photoionization Mass Spectrometry coupled to quasi-continuous tunable VUV synchrotron radiation at room temperature (295 K) and 90 oC (363 K), at 4 Torr (533 Pa). Laser photolysis of bromoform (CHBr3) at 248 nm (KrF excimer laser) is used to produce CH radicals that are free to react with pyrrole molecules in the gaseous mixture. A signal at m/z = 79 (C5H5N) is identified as the product of the reaction and resolved from 79Br atoms, and the result is consistent with CH addition to pyrrole followed by Helimination. The Photoionization Efficiency curve unambiguously identifies m/z = 79 as pyridine. With deuterated methylidyne radicals (CD), the product mass peak is shifted by +1 mass unit, consistent with the formation of C5H4DN and identified as deuterated pyridine (dpyridine). Within detection limits, there is no evidence that the addition intermediate complex undergoes hydrogen scrambling. The results are consistent with a reaction mechanism that proceeds via the direct CH (CD) cycloaddition or insertion into the five-member pyrrole ring, giving rise to ring expansion, followed by H atom elimination from the nitrogen atom in the intermediate to form the resonance stabilized pyridine (d-pyridine) molecule. Implications to interstellar chemistry and planetary atmospheres, in particular Titan, as well as in gas-phase combustion processes, are discussed.

  5. Synthesis of fused imidazoles, pyrroles, and indoles with a defined stereocenter α to nitrogen utilizing Mitsunobu alkylation followed by palladium-catalyzed cyclization.

    PubMed

    Laha, Joydev K; Cuny, Gregory D

    2011-10-21

    Nitrogen-containing fused heterocycles comprise many compounds that demonstrate interesting biological activities. A new synthetic approach involving Mitsunobu alkylation of imidazoles, pyrroles, and indoles followed by palladium-catalyzed cyclization has been developed providing access to fused heterocycles with a defined stereochemistry α to nitrogen. While ethyl imidazole or indole carboxylates are good substrates for Mitsunobu alkylation with optically pure secondary benzylic alcohols, the corresponding pyrroles are poor substrates presumably due to the increased pK(a) of the NH. The presence of a synthetically versatile trichloroacetyl functional group on the pyrroles significantly reduces the pK(a) and thereby facilitates Mitsunobu alkylation. Subsequent cyclization of the alkylated products mediated by palladium in the presence or absence of a ligand gave fused heterocycles in good to excellent yields.

  6. Pyridine-antipyrine appended indole derivative for selective recognition of Fe3 +: Concentration dependent coloration

    NASA Astrophysics Data System (ADS)

    Ta, Sabyasachi; Nandi, Sandip; Ghosh, Milan; Banerjee, Somenath; Das, Debasis

    2017-02-01

    Combination of pyridine, antipyrine and indole in a single molecule (L2) allows selective recognition of Fe3 + colorimetrically in CH3CN. The structure of L2 is confirmed from single crystal X-ray diffraction analysis. The probe displays two different visible bands at 541 nm and 715 nm in the presence of Fe3 +, associated with two different colors, viz. green and pink-violet allowing determination of unknown Fe3 + concentration. Interestingly, removal of 2-picolyl group from indole N-center of L2 generates L3 that behaves similarly at low Fe3 + concentration (> 0 to 1.1 mM) but differently at higher Fe3 + concentration (> 1.1 mM), indicating involvement of pyridyl-N donor towards Fe3 +, and hence different coordination environment around Fe3 + at higher concentration.

  7. Deproto-metallation of N-arylated pyrroles and indoles using a mixed lithium–zinc base and regioselectivity-computed CH acidity relationship

    PubMed Central

    Messaoud, Mohamed Yacine Ameur; Hedidi, Madani; Derdour, Aïcha; Chevallier, Floris; Ivashkevich, Oleg A; Matulis, Vadim E; Roisnel, Thierry; Dorcet, Vincent

    2015-01-01

    Summary The synthesis of N-arylated pyrroles and indoles is documented, as well as their functionalization by deprotonative metallation using the base in situ prepared from LiTMP and ZnCl2·TMEDA (1/3 equiv). With N-phenylpyrrole and -indole, the reactions were carried out in hexane containing TMEDA which regioselectively afforded the 2-iodo derivatives after subsequent iodolysis. With pyrroles and indoles bearing N-substituents such as 2-thienyl, 3-pyridyl, 4-methoxyphenyl and 4-bromophenyl, the reactions all took place on the substituent, at the position either adjacent to the heteroatom (S, N) or ortho to the heteroatom-containing substituent (OMe, Br). The CH acidities of the substrates were determined in THF solution using the DFT B3LYP method in order to rationalize the experimental results. PMID:26425204

  8. Trimethoxybenzene- and trimethylbenzene-based compounds bearing imidazole, indole and pyrrole groups as recognition units: synthesis and evaluation of the binding properties towards carbohydrates.

    PubMed

    Rosien, Jan-Ruven; Seichter, Wilhelm; Mazik, Monika

    2013-10-14

    The aim of the study was to evaluate the potential of trimethoxybenzene- and trimethylbenzene-based compounds bearing imidazole or indole groups as recognition sites in the complexation of carbohydrates. Representatives of these compounds were prepared and their binding properties toward selected carbohydrates evaluated. The results of the binding studies were compared with those obtained for the prepared pyrrole bearing analogues and for the previously described triethylbenzene-based receptors.

  9. Cobalt(II) Porphyrin-Catalyzed Intramolecular Cyclopropanation of N-Alkyl Indoles/Pyrroles with Alkylcarbene: Efficient Synthesis of Polycyclic N-Heterocycles.

    PubMed

    Reddy, Annapureddy Rajasekar; Hao, Fei; Wu, Kai; Zhou, Cong-Ying; Che, Chi-Ming

    2016-01-26

    A protocol on chemoselective cobalt(II) porphyrin-catalyzed intramolecular cyclopropanation of N-alkyl indoles/pyrroles with alkylcarbenes has been developed. The reaction enables the rapid construction of a range of nitrogen-containing polycyclic compounds in moderate to high yields from readily accessible materials. These N-containing polycyclic compounds can be converted into a variety of N-heterocycles with potential synthetic and biological interest. Compared to their N-tosylhydrazone counterparts, the use of bulky N-2,4,6-triisopropylbenzenesulfonyl hydrazones as carbene precursors allows cyclopropanation to occur under milder reaction conditions.

  10. Core Level Shifts of Hydrogenated Pyridinic and Pyrrolic Nitrogen in the Nitrogen-Containing Graphene-Based Electrocatalysts: In-Plane vs Edge Defects

    SciTech Connect

    Matanovic, Ivana; Artyushkova, Kateryna; Strand, Matthew B.; Dzara, Michael J.; Pylypenko, Svitlana; Atanassov, Plamen

    2016-12-07

    A combination of N 1s X-ray photoelectron spectroscopy (XPS) and first principles calculations of nitrogen-containing model electrocatalysts was used to elucidate the nature of the nitrogen defects that contribute to the binding energy (BE) range of the N 1s XPS spectra of these materials above ~400 eV. Experimental core level shifts were obtained for a set of model materials, namely N-doped carbon nanospheres, Fe–N–carbon nanospheres, polypyrrole, polypyridine, and pyridinium chloride, and were compared to the shifts calculated using density functional theory. The results confirm that the broad peak positioned at ~400.7 eV in the N 1s XPS spectra of N-containing catalysts, which is typically assigned to pyrrolic nitrogen, contains contributions from other hydrogenated nitrogen species such as hydrogenated pyridinic functionalities. Namely, N 1s BEs of hydrogenated pyridinic-N and pyrrolic-N were calculated as 400.6 and 400.7 eV, respectively, using the Perdew–Burke–Ernzerhof exchange-correlation functional. A special emphasis was placed on the study of the differences in the XPS imprint of N-containing defects that are situated in the plane and on the edges of the graphene sheet. Density functional theory calculations for BEs of the N 1s of in-plane and edge defects show that hydrogenated N defects are more sensitive to the change in the chemical environment in the carbon matrix than the non-hydrogenated N defects. In conclusion, calculations also show that edge-hydrogenated pyridinic-N and pyrrolic-N defects only contribute to the N 1s XPS peak located at ~400.7 eV if the graphene edges are oxygenated or terminated with bare carbon atoms.

  11. Core Level Shifts of Hydrogenated Pyridinic and Pyrrolic Nitrogen in the Nitrogen-Containing Graphene-Based Electrocatalysts: In-Plane vs Edge Defects

    DOE PAGES

    Matanovic, Ivana; Artyushkova, Kateryna; Strand, Matthew B.; ...

    2016-12-07

    A combination of N 1s X-ray photoelectron spectroscopy (XPS) and first principles calculations of nitrogen-containing model electrocatalysts was used to elucidate the nature of the nitrogen defects that contribute to the binding energy (BE) range of the N 1s XPS spectra of these materials above ~400 eV. Experimental core level shifts were obtained for a set of model materials, namely N-doped carbon nanospheres, Fe–N–carbon nanospheres, polypyrrole, polypyridine, and pyridinium chloride, and were compared to the shifts calculated using density functional theory. The results confirm that the broad peak positioned at ~400.7 eV in the N 1s XPS spectra of N-containingmore » catalysts, which is typically assigned to pyrrolic nitrogen, contains contributions from other hydrogenated nitrogen species such as hydrogenated pyridinic functionalities. Namely, N 1s BEs of hydrogenated pyridinic-N and pyrrolic-N were calculated as 400.6 and 400.7 eV, respectively, using the Perdew–Burke–Ernzerhof exchange-correlation functional. A special emphasis was placed on the study of the differences in the XPS imprint of N-containing defects that are situated in the plane and on the edges of the graphene sheet. Density functional theory calculations for BEs of the N 1s of in-plane and edge defects show that hydrogenated N defects are more sensitive to the change in the chemical environment in the carbon matrix than the non-hydrogenated N defects. In conclusion, calculations also show that edge-hydrogenated pyridinic-N and pyrrolic-N defects only contribute to the N 1s XPS peak located at ~400.7 eV if the graphene edges are oxygenated or terminated with bare carbon atoms.« less

  12. Crystal structure of 4-(2-azido-phen-yl)-5-benzoyl-2-(1H-indol-3-yl)-1H-pyrrole-3-carbo-nitrile.

    PubMed

    Vimala, G; Raja, J Kamal; Naaz, Y Amina; Preumal, P T; SubbiahPandi, A

    2015-05-01

    In the title compound, C26H16N6O, the dihedral angles between the central pyrrole ring and the pendant indole ring system (r.m.s. deviation = 0.027 Å) and the azide-bearing benzene ring are 37.56 (8) and 51.62 (11)°, respectively. The azide group is almost coplanar with its attached benzene ring [C-C-N-N = 3.8 (3)°]. The benzoyl benzene ring is disordered over two orientations twisted with respect to each other by 9.29 (8)° in a 0.514 (2):0.486 (2) ratio. In the crystal, inversion dimers linked by pairs of Np-H⋯O (p = pyrrole) hydrogen bonds generate R 2 (2)(10) loops. A second inversion dimer arises from a pair of Ni-H⋯Nc (i = indole and c = cyanide) hydrogen bonds, which generates an R 2 (2)(16) loop. Together, the hydrogen bonds lead to [011] chains in the crystal.

  13. Potency of photoinduced electron transfer and antioxidant efficacy of pyrrole and pyridine based Cu(II)-Schiff complexes while binding with CT-DNA.

    PubMed

    Koley Seth, Banabithi; Ray, Aurkie; Saha, Arpita; Saha, Partha; Basu, Samita

    2014-03-05

    Here we report a systematic and comparative study to define a correlation between the structure and function of a series of simple, biologically active small inorganic Schiff base copper complexes for the occurrence of charge transfer phenomenon in calf thymus DNA (CT-DNA) using transient absorption spectroscopy corroborated with magnetic field effect. Four copper(II) Schiff base complexes with differently substituted heterocyclic ligands with antioxidant activity have been used. The binding constants of the order of ∼ 10(4) support the moderate binding affinity of the complexes towards CT-DNA. The methyl-substituted pyrrole complex shows maximum binding affinity (Kb: 8.33 × 10(4)) compared to others. The occurrence of photoinduced electron transfer (PET) from CT-DNA to pyrrole containing complexes has been confirmed by identifying the corresponding transient radical ions whereas the extent of PET with pyridine substituted complexes is too small to be observed. The increase of the yield of radical ions in presence of magnetic field depicts that the initial spin correlation in geminate radical ion pair is triplet. The difference between experimental and calculated B½ values, the measure of hyperfine interactions (HFI) present in the system, arises due to hole hopping through intrastrand and interstrand DNA bases. The unsubstituted pyrrole complexes cleave DNA much more than the methyl-substituted one. Therefore, the probability of intrastrand superexchange increases with methyl-substituted complexes, that reduces the rate of hole hopping and hence the B½ value.

  14. Facile and promising method for michael addition of indole and pyrrole to electron-deficient trans-β-nitroolefins catalyzed by a hydrogen bond donor catalyst Feist's acid and preliminary study of antimicrobial activity.

    PubMed

    Al Majid, Abdullah M A; Islam, Mohammad Shahidul; Barakat, Assem; Al-Agamy, Mohamed H M; Naushad, Mu

    2014-01-01

    The importance of cooperative hydrogen-bonding effects has been demonstrated using novel 3-methylenecyclopropane-1,2-dicarboxylic acid (Feist's acid (FA)) as hydrogen bond donor catalysts for the addition of indole and pyrrole to trans-β-nitrostyrene derivatives. Because of the hydrogen bond donor (HBD) ability, Feist's acid (FA) has been introduced as a new class of hydrogen bond donor catalysts for the activation of nitroolefin towards nucleophilic substitution reaction. It has effectively catalyzed the Michael addition of indoles and pyrrole to β-nitroolefins under optimum reaction condition to furnish the corresponding Michael adducts in good to excellent yields (up to 98%). The method is general, atom-economical, convenient, and eco-friendly and could provide excellent yields and regioselectivities. Some newly synthesized compounds were for examined in vitro antimicrobial activity and their preliminary results are reported.

  15. Facile and Promising Method for Michael Addition of Indole and Pyrrole to Electron-Deficient trans-β-Nitroolefins Catalyzed by a Hydrogen Bond Donor Catalyst Feist's Acid and Preliminary Study of Antimicrobial Activity

    PubMed Central

    Al Majid, Abdullah M. A.; Islam, Mohammad Shahidul; Barakat, Assem; Al-Agamy, Mohamed H. M.; Naushad, Mu.

    2014-01-01

    The importance of cooperative hydrogen-bonding effects has been demonstrated using novel 3-methylenecyclopropane-1,2-dicarboxylic acid (Feist's acid (FA)) as hydrogen bond donor catalysts for the addition of indole and pyrrole to trans-β-nitrostyrene derivatives. Because of the hydrogen bond donor (HBD) ability, Feist's acid (FA) has been introduced as a new class of hydrogen bond donor catalysts for the activation of nitroolefin towards nucleophilic substitution reaction. It has effectively catalyzed the Michael addition of indoles and pyrrole to β-nitroolefins under optimum reaction condition to furnish the corresponding Michael adducts in good to excellent yields (up to 98%). The method is general, atom-economical, convenient, and eco-friendly and could provide excellent yields and regioselectivities. Some newly synthesized compounds were for examined in vitro antimicrobial activity and their preliminary results are reported. PMID:24574906

  16. Mimicking Trimeric Interactions in the Aromatic Side Chains of the Proteins: a Gas Phase Study of INDOLE...(PYRROLE)_2 Heterotrimer

    NASA Astrophysics Data System (ADS)

    Das, Aloke; Kumar, Sumit

    2012-06-01

    Aromatic trimeric interactions are extremely important in the stabilization of the specific structures of the proteins as well as protein-protein, and protein-ligand interactions. Here I will present a direct evidence of the observation of a cyclic asymmetric structure of indole...(pyrrole)_2 trimer bound by three N-H...π hydrogen bonding interactions in a supersonic jet. The experiment has been performed by using resonant two-photon ionization (R2PI), IR-UV, and UV-UV double resonance spectroscopic techniques. Density functional theory (DFT) calculations nicely corroborate the experimental results showing one weakly allowed IR-active band due to symmetric stretch of the N-H bonds and two strongly allowed IR-active bands due to two types of asymmetric stretches of the N-H bonds in the trimer. The most significant finding of the present investigation is that there is a direct IR spectral signature for the determination of the geometry of a trimer if it has a cyclic asymmetric structure.

  17. Pyridine

    Integrated Risk Information System (IRIS)

    Pyridine ; CASRN 110 - 86 - 1 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Noncarcinogenic Effects

  18. A Dual-Responsive Bola-Type Supra-amphiphile Constructed from a Water-Soluble Calix[4]pyrrole and a Tetraphenylethene-Containing Pyridine Bis-N-oxide.

    PubMed

    Chi, Xiaodong; Zhang, Huacheng; Vargas-Zúñiga, Gabriela I; Peters, Gretchen M; Sessler, Jonathan L

    2016-05-11

    Complexation between a water-soluble calix[4]pyrrole and a ditopic pyridine N-oxide derivative in aqueous media produces a bola-type supra-amphiphile that self-assembles to produce higher order morphologies, including multilamellar vesicles and micelles depending on the pH. The present bola-type supra-amphiphile exhibits strong fluorescence due to structural changes and aggregation induced by host-guest complexation. The resulting structures may be used to recognize, encapsulate, and release non-fluorescent, water-soluble small molecules.

  19. Benzo[g]indoles

    NASA Astrophysics Data System (ADS)

    Pozharskii, A. F.; Kachalkina, S. G.; Gulevskaya, A. V.; Filatova, E. A.

    2017-07-01

    The data on the synthesis and properties of benzo[g]indoles accumulated mainly over a period of the past 15-20 years are integrated. Various variants of pyrrole ring and naphthalene nucleus closure are considered. It is demonstrated that, in addition to the expected similarity between benzo[g]indoles and indoles, there are noticeable differences between them as well, especially where the synthesis of the benzoindole system is concerned. Practical applications of benzo[g]indoles are discussed. The bibliography includes 199 references.

  20. Synthesis, biological evaluation and molecular docking study of some novel indole and pyridine based 1,3,4-oxadiazole derivatives as potential antitubercular agents.

    PubMed

    Desai, N C; Somani, Hardik; Trivedi, Amit; Bhatt, Kandarp; Nawale, Laxman; Khedkar, Vijay M; Jha, Prakash C; Sarkar, Dhiman

    2016-04-01

    A series of indole and pyridine based 1,3,4-oxadiazole derivatives 5a-t were synthesized and evaluated for their in vitro antitubercular activity against Mycobacterium tuberculosis H37Ra (MTB) and Mycobacterium bovis BCG both in active and dormant state. Compounds 5b, 5e, 5g and 5q exhibited very good antitubercular activity. All the newly synthesized compounds 5a-t were further evaluated for anti-proliferative activity against HeLa, A549 and PANC-1 cell lines using modified MTT assay and found to be noncytotoxic. On the basis of cytotoxicity and MIC values against Mycobacterium bovis BCG, selectivity index (SI) of most active compounds 5b, 5e, 5g and 5q was calculated (SI=GI50/MIC) in active and dormant state. Compounds 5b, 5e and 5g demonstrated SI values ⩾10 against all three cell lines and were found to safe for advance screening. Compounds 5a-t were further screened for their antibacterial activity against four bacteria strains to assess their selectivity towards MTB. In addition, the molecular docking studies revealed the binding modes of these compounds in active site of enoyl reductase (InhA), which in turn helped to establish a structural basis of inhibition of mycobacteria. The potency, low cytotoxicity and selectivity of these compounds make them valid lead compounds for further optimization.

  1. A Quasi-relativistic Density Functional Theory Study of the Actinyl(VI, V) (An = U, Np, Pu) Complexes with a Six-Membered Macrocycle Containing Pyrrole, Pyridine, and Furan Subunits.

    PubMed

    Lan, Jian-Hui; Wang, Cong-Zhi; Wu, Qun-Yan; Wang, Shu-Ao; Feng, Yi-Xiao; Zhao, Yu-Liang; Chai, Zhi-Fang; Shi, Wei-Qun

    2015-08-27

    Actinyl(VI, V) (An = U, Np and Pu) complexes of the recently reported hybrid macrocycle, cyclo[1]furan[1]pyridine[4]pyrrole (denoted as H4L), have been studied using density functional theory in combination with the small-core scalar-relativistic effective core potentials and corresponding (14s13p10d8f6g)/[ 10s9p5d4f3g] basis sets in the segmented contraction scheme. On the basis of our calculations, the pyrrole nitrogen atoms that possess the shortest An-L bonds and strongest basicity are the main donor atoms that contribute to the formation of actinyl(VI, V) complexes. The natural population analysis (NPA) suggests higher ligand-to-actinyl charge transfer in the actinyl(VI) complexes than in their actinyl(V) analogues, which account for the higher decomposition energies of the former. A significant actinide-to-ligand spin density delocalization in the uranyl(V) and neptunyl(V) complexes was observed owing to the redistribution of spin density caused by complexation. A thermodynamic analysis indicates that the formation of the actinyl(VI, V) complexes are exothermic reactions in CH2Cl2 solvent, where the uranyl cations show the highest selectivity. In aqueous solution containing chloride ions, for complexing with macrocycle H4L, the plutonyl(VI) and uranyl(V) cations possess the highest selectivity among actinyl(VI) and (V) cations, respectively. This work can shed light on the design of macrocycle complexes for actinide recognition and extraction in the future.

  2. Structures of hydrazones, (E)-2-(1,3-benzothiazolyl)-NHsbnd Ndbnd CHsbnd Ar, [Ar = 4-(pyridin-2-yl)phenyl, pyrrol-2-yl, thien-2-yl and furan-2-yl]: Difference in conformations and intermolecular hydrogen bonding

    NASA Astrophysics Data System (ADS)

    Lindgren, Eric B.; Yoneda, Julliane D.; Leal, Katia Z.; Nogueira, Antônio F.; Vasconcelos, Thatyana R. A.; Wardell, James L.; Wardell, Solange M. S. V.

    2013-03-01

    Structures of hydrazones, (E)-2-(1,3-benzothiazolyl)-NHsbnd Ndbnd CHsbnd Ar(Ar = pyridine-2-yl (1), pyrrol-2-yl (2), thien-2-yl (3) and furan-2-yl (4), prepared from 2-hydrazinyl-1,3-benzothiazole and ArCHO, followed by recrystallisation from alcohol solutions, are reported. No significant intramolecular hydrogen bonds are present in any of the four molecules. Different conformations were found between 2 and 3, on one hand and for 4, on the other. Thus for 4, the oxygen atom of the furanyl ring is on the same side of the molecule as is the sulfur atom of the benzothiazole unit, while in contrast, each of the heteroatoms of the thienyl and pyrrole rings lies on opposite sides to the benzothiazole sulphur atom. In addition to the conformational variations, differences are noted in the connections between molecules. Despite the presence in each case of N(hydrazono)sbnd H---N(benzothiazolo) intermolecular hydrogen bonds, molecules of 4 are linked into spiral chains, while molecules of 2 and 3 (and indeed all compounds having Ar = substituted phenyl) form symmetric dimers. Further intermolecular interactions, albeit weaker ones, are found in 2 [Csbnd H··N and Nsbnd H··π], 3 [Csbnd H··π] and 4 [π··π], while dimers of 1 remain essentially free. Calculations carried out using the DFT(B3LYP)/6-311++G(d,p) method indicated that the conformations determined by crystallography for 2-4 were the more stable.

  3. Crystal structure of 4,4'-[(1,3,5,7-tetra-oxo-1,3,3a,4,4a,5,7,7a,8,8a-deca-hydro-4,8-etheno-pyrrolo-[3,4-f]iso-indole-2,6-di-yl)bis-(methyl-ene)]bis-(pyridin-1-ium) dinitrate.

    PubMed

    Liu, Zhimin

    2015-12-01

    In the title salt, C24H22N4O4 (2+)·2NO3 (-), the cation is U-shaped with the two iso-indole dione rings inclined to one another by 60.41 (13)°, while the two outer pyridine rings are inclined to one another by 2.77 (12)°. The dihedral angles between the pyridine ring and the adjacent iso-indole dione ring are 71.82 (12) and 86.44 (13)°. In the crystal, each nitrate anion is linked to a protonated pyridine ring by N-H⋯O hydrogen bonds. These units are linked by a series of C-H⋯O hydrogen bonds, forming a three-dimensional structure.

  4. Enantioselective and Regioselective Indium(III)-Catalyzed Addition of Pyrroles to Isatins

    PubMed Central

    Gutierrez, Elisa G.; Wong, Casey J.; Sahin, Aziza H.

    2011-01-01

    The indium(III)-catalyzed enantioselective and regioselective addition of pyrroles to isatins is described. The effects of metal and solvent on the reactivity and selectivity are compared and discussed, demonstrating that the indium(III)-indapybox complex provides the most effective catalyst. A case of divergent reactivity between pyrroles and indoles is presented. PMID:21992567

  5. 1-(2-Hy-droxy-eth-yl)-3-[(2-hy-droxy-eth-yl)amino]-4-(1H-indol-3-yl)-1H-pyrrole-2,5-dione.

    PubMed

    Xie, Zhi-Xiong; Zhao, Sheng-Yin

    2011-04-01

    There are four molecules in the asymmetric unit of the title compound, C(16)H(17)N(3)O(4), in which the dihedral angles between the indole ring system and maleimide ring are 4.5 (3), 8.3 (3), 8.4 (2) and 10.4 (2)°. In the crystal, mol-ecules are linked by numerous N-H⋯O and O-H⋯O hydrogen bonds, generating a three-dimensional network.

  6. Measurement of the Heterocyclic Amines 2-Amino-9H-pyrido[2,3-b]indole and 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine in Urine: Effects of Cigarette Smoking

    PubMed Central

    Konorev, Dmitri; Koopmeiners, Joseph S.; Tang, Yijin; Franck Thompson, Elizabeth A.; Jensen, Joni A.; Hatsukami, Dorothy K.; Turesky, Robert J.

    2015-01-01

    2-Amino-9H-pyrido[2,3-b]indole (AαC) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) are carcinogenic heterocyclic aromatic amines (HAAs) formed during the combustion of tobacco and during the high-temperature cooking of meats. Human enzymes biotransform AαC and PhIP into reactive metabolites, which can bind to DNA and lead to mutations. We sought to understand the relative contribution of smoking and diet to the exposure of AαC and PhIP, by determining levels of AαC, its ring-oxidized conjugate 2-amino-9H-pyrido[2,3-b]indole-3-yl sulfate (AαC-3-OSO3H), and PhIP in urine of smokers on a free-choice diet before and after a six week tobacco smoking cessation study. AαC and AαC-3-OSO3H were detected in more than 90% of the urine samples of all subjects during the smoking phase. The geometric mean levels of urinary AαC during the smoking and cessation phases were 24.3 pg/mg creatinine and 3.2 pg/mg creatinine, and the geometric mean levels of AαC-3-OSO3H were 47.3 pg/mg creatinine and 3.7 pg/mg creatinine. These decreases in the mean levels of AαC and AαC-3-OSO3H were, respectively, 87% and 92%, after the cessation of tobacco (P < 0.0007). However, PhIP was detected in < 10% of the urine samples, and the exposure to PhIP was not correlated to smoking. Epidemiological studies have reported that smoking is a risk factor for cancer of the liver and gastrointestinal tract. It is noteworthy that AαC is a hepatocellular carcinogen and induces aberrant crypt foci, early biomarkers of colon cancer, in rodents. Our urinary biomarker data demonstrate that tobacco smoking is a significant source of AαC exposure. Further studies are warranted to examine the potential role of AαC as a risk factor for hepatocellular and gastrointestinal cancer in smokers. PMID:26574651

  7. 1-(2-Hy­droxy­eth­yl)-3-[(2-hy­droxy­eth­yl)amino]-4-(1H-indol-3-yl)-1H-pyrrole-2,5-dione

    PubMed Central

    Xie, Zhi-Xiong; Zhao, Sheng-Yin

    2011-01-01

    There are four molecules in the asymmetric unit of the title compound, C16H17N3O4, in which the dihedral angles between the indole ring system and maleimide ring are 4.5 (3), 8.3 (3), 8.4 (2) and 10.4 (2)°. In the crystal, mol­ecules are linked by numerous N—H⋯O and O—H⋯O hydrogen bonds, generating a three-dimensional network. PMID:21754135

  8. The ceiling effect of pharmacological postconditioning with the phytoestrogen genistein is reversed by the GSK3beta inhibitor SB 216763 [3-(2,4-dichlorophenyl)-4(1-methyl-1H-indol-3-yl)-1H-pyrrole-2,5-dione] through mitochondrial ATP-dependent potassium channel opening.

    PubMed

    Couvreur, Nicolas; Tissier, Renaud; Pons, Sandrine; Chenoune, Mourad; Waintraub, Xavier; Berdeaux, Alain; Ghaleh, Bijan

    2009-06-01

    In the present study, we investigated the efficacy of pharmacological postconditioning induced by 17beta-estradiol and the phytoestrogen, genistein, against myocardial infarction induced by increasing durations of coronary artery occlusion (CAO). Anesthetized rabbits underwent either 20-min (protocol A) or 30-min (protocol B) CAO, followed by 4 h of coronary artery reperfusion (CAR). Before CAR, they randomly received an intravenous injection of either vehicle (control), 100 or 1000 microg/kg genistein (Geni(100) and Geni(1000), respectively), or 100 microg/kg 17beta-estradiol (17beta-E(100)). In protocol A, infarct size was significantly reduced in Geni(100) (n = 6), Geni(1000) (n = 6), and 17beta-E(100) (n = 6) versus control (n = 9) (6 +/- 2, 15 +/- 4, and 11 +/- 3 versus 35 +/- 5%, respectively). In protocol B, none of these drugs reduced infarct size versus control. Western blots demonstrated an increase of Akt phosphorylation in the Geni(100) and 17beta-E(100) hearts submitted to 20-min CAO but not to 30-min CAO. The selective GSK3beta inhibitor SB 216763 (0.2 mg/kg) [3-(2,4)-dichlorophenyl)-4(1-methyl-1H-indol-3-yl)-1H-pyrrole-2,5-dione] did not exhibit cardioprotection at this dose, but its administration restored the cardioprotective effect of genistein and 17beta-estradiol with 30-min CAO. Administration of 5-hydroxydecanoate (5 mg/kg) abolished the cardioprotective effects of Geni(100) and 17beta-E(100) alone with 20-min CAO and also those observed when combined to SB 216763 with 30-min CAO. Thus, pharmacological postconditioning with genistein and 17beta-estradiol is limited by a "ceiling effect of protection" along with a loss of Akt phosphorylation. However, this ceiling effect is reversed by concomitant inhibition of GSK3beta by SB 216763 through opening of mitochondrial ATP-dependent potassium channels.

  9. Organocatalytic Enantioselective Aza-Friedel-Crafts Reaction of Cyclic Ketimines with Pyrroles using Imidazolinephosphoric Acid Catalysts.

    PubMed

    Nakamura, Shuichi; Matsuda, Nazumi; Ohara, Mutsuyo

    2016-07-04

    Organocatalytic enantioselective aza-Friedel-Crafts reactions of cyclic ketimines with pyrroles or indoles were catalyzed by imidazoline/phosphoric acid catalysts. The reaction was applied to various 3H-indol-3-ones to afford products in excellent yields and enantioselectivities. The chiral catalysts can be recovered by a single separation step using column chromatography and are reusable without further purification. Based on the experimental investigations, a possible transition state has been proposed to explain the origin of the asymmetric induction.

  10. Ruthenium-catalyzed direct C3 alkylation of indoles with α,β-unsaturated ketones.

    PubMed

    Li, Shuai-Shuai; Lin, Hui; Zhang, Xiao-Mei; Dong, Lin

    2015-01-28

    In this paper, a simple and highly efficient ruthenium-catalyzed direct C3 alkylation of indoles with various α,β-unsaturated ketones without chelation assistance has been developed. This novel C-H activation methodology exhibits a broad substrate scope such as different substituted indoles, pyrroles, and other azoles. Further synthetic applications of the alkylation products can lead to more attractive 3,4-fused tricyclic indoles.

  11. Friedel-Crafts Hydroxyalkylation of Indoles Mediated by Trimethylsilyl Trifluoromethanesulfonate.

    PubMed

    Downey, C Wade; Poff, Christopher D; Nizinski, Alissa N

    2015-10-16

    Indoles and N-alkylindoles undergo Friedel-Crafts addition to aldehydes in the presence of trimethylsilyl trifluoromethanesulfonate and a trialkylamine to produce 3-(1-silyloxyalkyl)indoles. Neutralization of the reaction mixture with pyridine followed by deprotection under basic conditions with tetrabutylammonium fluoride provides the 1:1 adduct as the free alcohol. This method prevents spontaneous conversion of the desired products to the thermodynamically favored bisindolyl(aryl)methanes, a process typically observed when indoles are reacted with aldehydes under acidic conditions.

  12. An indole-linked C8-deoxyguanosine nucleoside acts as a fluorescent reporter of Watson-Crick versus Hoogsteen base pairing.

    PubMed

    Schlitt, Katherine M; Millen, Andrea L; Wetmore, Stacey D; Manderville, Richard A

    2011-03-07

    Pyrrole- and indole-linked C(8)-deoxyguanosine nucleosides act as fluorescent reporters of H-bonding specificity. Their fluorescence is quenched upon Watson-Crick H-bonding to dC, while Hoogsteen H-bonding to G enhances emission intensity. The indole-linked probe is ∼ 10-fold brighter and shows promise as a fluorescent reporter of Hoogsteen base pairing.

  13. Synthesis of annulated bis-indoles through Au(i)/Brønsted acid-catalyzed reactions of (1H-indol-3-yl)(aryl)methanols with 2-(arylethynyl)-1H-indoles.

    PubMed

    Inamdar, Suleman M; Gonnade, Rajesh G; Patil, Nitin T

    2017-01-25

    A general method to access annulated bis-indoles from (1H-indol-3-yl)(aryl)methanols and 2-(arylethynyl)-1H-indoles under the catalysis of the Ph3PAuOTf/Brønsted acid binary catalyst system has been developed. The reaction was found to proceed in a highly efficient manner and benefit from easy-to-make starting materials, broad substrate scope and operational simplicity. The potential of this method has also been exemplified for the synthesis of pyrrole-annulated indoles using 2-(phenylethynyl)-1H-indoles and phenyl(1H-pyrrol-2-yl)methanols. Furthermore, the use of a ternary catalyst system, involving PdCl2/Brønsted acid/Ph3PAuOTf catalysts, has been realized for the synthesis of annulated bis-indoles starting directly from 2-(phenylbuta-1,3-diyn-1-yl)aniline and (1H-indol-3-yl)(aryl)methanol. Mechanistically, this reaction is very interesting since the overall process involves three different catalytic cycles catalyzed by three different catalysts in a relay fashion.

  14. Phosphine-mediated cascade reaction of azides with MBH-acetates of acetylenic aldehydes to substituted pyrroles: a facile access to N-fused pyrrolo-heterocycles.

    PubMed

    Reddy, Chada Raji; Reddy, Motatipally Damoder; Srikanth, Boinapally

    2012-06-07

    One-pot synthesis of substituted pyrroles by a cascade reaction of azides with Morita-Baylis-Hillman acetates of acetylenic aldehydes is described and the reaction is efficiently mediated by triphenyl phosphine at room temperature. Sodium azide is successfully used to provide N-unsubstituted pyrroles, while alkyl azides afforded the corresponding N-alkylated pyrroles through a sequence of allylic substitution/azide reduction/cycloisomerization reactions. The obtained products have provided a new entry to indolizino indoles, pyrrolo isoquinolines and 8-oxo-5,6,7,8-tetrahydroindolizine.

  15. Synthetic tripodal receptors for carbohydrates. Pyrrole, a hydrogen bonding partner for saccharidic hydroxyls.

    PubMed

    Francesconi, Oscar; Gentili, Matteo; Roelens, Stefano

    2012-09-07

    The carbohydrate recognition properties of synthetic tripodal receptors relying on H-bonding interactions have highlighted the crucial role played by the functional groups matching saccharidic hydroxyls. Herein, pyrrole and pyridine, which emerged as two of the most effective H-bonding groups, were quantitatively compared through their isostructural substitution within the architecture of a shape-persistent bicyclic cage receptor. NMR and ITC binding studies gave for the pyrrolic receptor a 20-fold larger affinity toward octyl-β-d-glucopyranoside in CDCl(3), demonstrating the superior recognition properties of pyrrole under conditions in which differences would depend on the intrinsic binding ability of the two groups. The three-dimensional structures of the two glucoside complexes in solution were elucidated by combined NMR and molecular mechanics computational techniques, showing that the origin of the stability difference between the two closely similar complex structures resides in the ability of pyrrole to establish shorter/stronger H-bonds with the glucosidic ligand compared to pyridine.

  16. A sustainable catalytic pyrrole synthesis

    NASA Astrophysics Data System (ADS)

    Michlik, Stefan; Kempe, Rhett

    2013-02-01

    The pyrrole heterocycle is a prominent chemical motif and is found widely in natural products, drugs, catalysts and advanced materials. Here we introduce a sustainable iridium-catalysed pyrrole synthesis in which secondary alcohols and amino alcohols are deoxygenated and linked selectively via the formation of C-N and C-C bonds. Two equivalents of hydrogen gas are eliminated in the course of the reaction, and alcohols based entirely on renewable resources can be used as starting materials. The catalytic synthesis protocol tolerates a large variety of functional groups, which includes olefins, chlorides, bromides, organometallic moieties, amines and hydroxyl groups. We have developed a catalyst that operates efficiently under mild conditions.

  17. 3-[4-(1H-Indol-3-yl)-1,3-thiazol-2-yl]-1H-pyrrolo[2,3-b]pyridines, Nortopsentin Analogues with Antiproliferative Activity

    PubMed Central

    Parrino, Barbara; Carbone, Anna; Di Vita, Gloria; Ciancimino, Cristina; Attanzio, Alessandro; Spanò, Virginia; Montalbano, Alessandra; Barraja, Paola; Tesoriere, Luisa; Livrea, Maria Antonia; Diana, Patrizia; Cirrincione, Girolamo

    2015-01-01

    A new series of nortopsentin analogues, in which the imidazole ring of the natural product was replaced by thiazole and the indole unit bound to position 2 of the thiazole ring was substituted by a 7-azaindole moiety, was efficiently synthesized. Two of the new nortopsentin analogues showed good antiproliferative effect against the totality of the NCI full panel of human tumor cell lines (~60) having GI50 values ranging from low micromolar to nanomolar level. The mechanism of the antiproliferative effect of these derivatives, investigated on human hepatoma HepG2 cells, was pro-apoptotic, being associated with externalization of plasma membrane phosphatidylserine and mitochondrial dysfunction. Moreover, the compounds induced a concentration-dependent accumulation of cells in the subG0/G1phase, while confined viable cells in G2/M phase. PMID:25854642

  18. 3-[4-(1H-indol-3-yl)-1,3-thiazol-2-yl]-1H-pyrrolo[2,3-b]pyridines, nortopsentin analogues with antiproliferative activity.

    PubMed

    Parrino, Barbara; Carbone, Anna; Di Vita, Gloria; Ciancimino, Cristina; Attanzio, Alessandro; Spanò, Virginia; Montalbano, Alessandra; Barraja, Paola; Tesoriere, Luisa; Livrea, Maria Antonia; Diana, Patrizia; Cirrincione, Girolamo

    2015-04-03

    A new series of nortopsentin analogues, in which the imidazole ring of the natural product was replaced by thiazole and the indole unit bound to position 2 of the thiazole ring was substituted by a 7-azaindole moiety, was efficiently synthesized. Two of the new nortopsentin analogues showed good antiproliferative effect against the totality of the NCI full panel of human tumor cell lines (~60) having GI50 values ranging from low micromolar to nanomolar level. The mechanism of the antiproliferative effect of these derivatives, investigated on human hepatoma HepG2 cells, was pro-apoptotic, being associated with externalization of plasma membrane phosphatidylserine and mitochondrial dysfunction. Moreover, the compounds induced a concentration-dependent accumulation of cells in the subG0/G1phase, while confined viable cells in G2/M phase.

  19. Paramagnetic nuclear magnetic resonance relaxation and molecular mechanics studies of the chloroperoxidase-indole complex: insights into the mechanism of chloroperoxidase-catalyzed regioselective oxidation of indole.

    PubMed

    Zhang, Rui; He, Qinghao; Chatfield, David; Wang, Xiaotang

    2013-05-28

    To unravel the mechanism of chloroperoxidase (CPO)-catalyzed regioselective oxidation of indole, we studied the structure of the CPO-indole complex using nuclear magnetic resonance (NMR) relaxation measurements and computational techniques. The dissociation constant (KD) of the CPO-indole complex was calculated to be approximately 21 mM. The distances (r) between protons of indole and the heme iron calculated via NMR relaxation measurements and molecular docking revealed that the pyrrole ring of indole is oriented toward the heme with its 2-H pointing directly at the heme iron. Both KD and r values are independent of pH in the range of 3.0-6.5. The stability and structure of the CPO-indole complex are also independent of the concentration of chloride or iodide ion. Molecular docking suggests the formation of a hydrogen bond between the NH group of indole and the carboxyl O of Glu 183 in the binding of indole to CPO. Simulated annealing of the CPO-indole complex using r values from NMR experiments as distance restraints reveals that the van der Waals interactions were much stronger than the Coulomb interactions in the binding of indole to CPO, indicating that the association of indole with CPO is primarily governed by hydrophobic rather than electrostatic interactions. This work provides the first experimental and theoretical evidence of the long-sought mechanism that leads to the "unexpected" regioselectivity of the CPO-catalyzed oxidation of indole. The structure of the CPO-indole complex will serve as a lighthouse in guiding the design of CPO mutants with tailor-made activities for biotechnological applications.

  20. Paramagnetic NMR Relaxation and Molecular Mechanics Studies of Chloroperoxidase-Indole Complex: Insights into the Mechanism of Chloroperoxidase-Catalyzed Regioselective Oxidation of Indole

    PubMed Central

    Zhang, Rui; He, Qinghao; Chatfield, David; Wang, Xiaotang

    2013-01-01

    To unravel the mechanism of CPO-catalyzed regioselective oxidation of indole, the structure of the CPO-indole complex was studied using NMR relaxation measurements and computational techniques. The dissociation constant (KD) of the CPO-indole complex was calculated to be approximately 21 mM. The distances (r) between protons of indole and the heme iron calculated from NMR relaxation measurements and molecular docking revealed that the pyrrole ring of indole is oriented toward the heme with its 2-H pointing directly at the heme iron. Both KD and r values are independent of pH in the range of 3.0–6.5. The stability and structure of the CPO-indole complex are also independent of the concentration of chloride/iodide ion. Molecular docking suggests the formation of a hydrogen bond between the N–H of indole and the carboxyl O of Glu 183 in the binding of indole to CPO. Simulated annealing of the CPO-indole complex using r values from NMR experiments as distance restraints reveals that the van der Waals interactions were much stronger than the Coulomb interactions in indole binding to CPO, indicating that the association of indole with CPO is primarily governed by hydrophobic rather than electrostatic interactions. This work provides the first experimental and theoretical evidence for the long-sought mechanism that leads to the “unexpected” regioselectivity of CPO-catalyzed oxidation of indole. The structure of the CPO-indole complex will serve as a lighthouse in guiding the design of CPO mutants with tailor-made activities for biotechnological applications. PMID:23634952

  1. Pyrrolnitrin analogues. V. Knorr's pyrrole condensation between N-(4-nitrophenacyl)-3,5-dimethylaniline and ethyl acetoacetate.

    PubMed

    Filacchioni, G; Artico, M; Brosio, E; Conti, F

    1978-01-01

    The reaction between N-(4-nitrophenacyl)-3,5-dimethylaniline and ethyl acetoacetate in boiling ethanol afforded 3-carbethoxy-5-(1-carbethoxyacetonyl)-4,5-dihydro-1-(3,5-dimethylphenyl)-4-hydroxy-2-methyl-4-(4-nitrophenyl)pyrrole and in low yield 3-carbethoxy-1-(3,5-dimethylphenyl)-2-methyl-4-(4-nitrophenyl)pyrrole. Chemical transformation of the former compound into 5-acetonyl-1-(3,5-dimethylphenyl)-2-methyl-4-(4-nitrophenyl)pyrrole is described. The structure of 3-carbethoxy-5-(1-carbethoxyacetonyl)-4,5-dihydro-1-(3,5-dimethylphenyl)-4-hydroxy-2-methyl-4-(4-nitrophenyl)pyrrole has been established by the aid of N.M.R. spectral data. The above reaction, when carried out in boiling ethanol in the presence of a catalytic amount of 3,5-dimethylaniline hydrobromide, led to the formation of 3-carbethoxy-1-(3,5-dimethylphenyl)-2-methyl-4-(4-nitrophenyl)pyrrole and 4,6-dimethyl-2-(4-nitrophenyl)indole, the former formed in a very good yield. Some pyrrolnitrin analogues have been prepared starting from 3-carbethoxy-1-(3,5-dimethylphenyl)-2-methyl-4-(4-nitrophenyl)pyrrole.

  2. Origins of Regioselectivity in the Fischer Indole Synthesis of a Selective Androgen Receptor Modulator.

    PubMed

    Noey, Elizabeth L; Yang, Zhongyue; Li, Yanwei; Yu, Hannah; Richey, Rachel N; Merritt, Jeremy M; Kjell, Douglas P; Houk, K N

    2017-06-02

    The selective androgen receptor modulator, (S)-(7-cyano-4-(pyridin-2-ylmethyl)-1,2,3,4-tetrahydrocyclopenta[b]indol-2-yl)carbamic acid isopropyl ester, LY2452473, is a promising treatment of side effects of prostate cancer therapies. An acid-catalyzed Fischer indolization is a central step in its synthesis. The reaction leads to only one of the two possible indole regioisomers, along with minor decomposition products. Computations show that the formation of the observed indole is most favored energetically, while the potential pathway to the minor isomer leads instead to decomposition products. The disfavored [3,3]-sigmatropic rearrangement, which would produce the unobserved indole product, is destabilized by the electron-withdrawing phthalimide substituent. The most favored [3,3]-sigmatropic rearrangement transition state is bimodal, leading to two reaction intermediates from one transition state, which is confirmed by molecular dynamics simulations. Both intermediates can lead to the observed indole product, albeit through different mechanisms.

  3. Marine Indole Alkaloids

    PubMed Central

    Netz, Natalie; Opatz, Till

    2015-01-01

    Marine indole alkaloids comprise a large and steadily growing group of secondary metabolites. Their diverse biological activities make many compounds of this class attractive starting points for pharmaceutical development. Several marine-derived indoles were found to possess cytotoxic, antineoplastic, antibacterial and antimicrobial activities, in addition to the action on human enzymes and receptors. The newly isolated indole alkaloids of marine origin since the last comprehensive review in 2003 are reported, and biological aspects will be discussed. PMID:26287214

  4. Pyrrole and Fused Pyrrole Compounds with Bioactivity against Inflammatory Mediators.

    PubMed

    Said Fatahala, Samar; Hasabelnaby, Sherifa; Goudah, Ayman; Mahmoud, Ghada I; Helmy Abd-El Hameed, Rania

    2017-03-17

    A new series of pyrrolopyridines and pyrrolopyridopyrimidines have been synthesized from aminocyanopyrroles. The synthesized compounds have been characterized by FTIR, ¹H-NMR and mass spectroscopy. The final compounds have been screened for in vitro pro-inflammatory cytokine inhibitory and in vivo anti-inflammatory activity. The biological results revealed that among all tested compounds some fused pyrroles, namely the pyrrolopyridines 3i and 3l, show promising activity. A docking study of the active synthesized molecules confirmed the biological results and revealed a new binding pose in the COX-2 binding site.

  5. Synthesis of Pyrido[1,2-a]indole Malonates and Amines through Aryne Annulation

    PubMed Central

    Rogness, Donald C.; Markina, Nataliya A.; Waldo, Jesse P.; Larock, Richard C.

    2012-01-01

    Pyrido[1,2-a]indoles are known as medicinally and pharmaceutically important compounds, but there is a lack of efficient methods for their synthesis. We report a convenient and efficient route to these privileged structures starting from easily accessible 2-substituted pyridines and aryne precursors. A small library of compounds has been synthesized utilizing the developed method, affording variously substituted pyrido[1,2-a]indoles in moderate to good yields. PMID:22356459

  6. Cyclo[n]pyrroles and methods thereto

    DOEpatents

    Sessler, Jonathan L.; Seidel, Daniel; Bolze, Frederic R.; Koehler, Thomas

    2006-01-10

    The present invention provides an oxidative coupling procedure that allows efficient synthesis of novel cyclo[n]pyrrole macrocycles. Therefore, the present invention provides cyclo[n]pyrroles where n is 6, 7, 8, 9, 10, 11, or 12, and derivatives, multimers, isomers, and ion and neutral molecule complexes thereof as new compositions of matter. A protonated form of cyclo[n]pyrrole displays a gap of up to 700 nm between strong Soret and Q-like absorption bands in the electronic spectrum, demonstrating no significant ground state absorption in the visible portion of the electronic spectrum. Uses of cyclo[n]pyrroles as separation media, nonlinear optical materials, information storage media and infrared filters are provided.

  7. Study of 1-deoxy-1-(indol-3-yl)-L-sorbose, 1-deoxy-1-(indol-3-yl)-L-tagatose, and their analogs.

    PubMed

    Lavrenov, Sergey N; Korolev, Alexander M; Reznikova, Marina I; Sosnov, Andrey V; Preobrazhenskaya, Maria N

    2003-01-20

    Alkaline degradation of the ascorbigen 2-C-[(indol-3-yl)methyl]-alpha-L-xylo-hex-3-ulofuranosono-1,4-lactone (1a) led to a mixture of 1-deoxy-1-(indol-3-yl)-L-sorbose (2a) and 1-deoxy-1-(indol-3-yl)-L-tagatose (3a). The mixture of diastereomeric ketoses underwent acetylation and pyranose ring opening under the action of acetic anhydride in pyridine in the presence of 4-dimethylaminopyridine (DMAP) with the formation of a mixture of (E)-2,3,4,5,6-penta-O-acetyl-1-deoxy-1-(indol-3-yl)-L-xylo-hex-1-enitol (4a) and (E)-2,3,4,5,6-penta-O-acetyl-1-deoxy-1-(indol-3-yl)-L-lyxo-hex-1-enitol (5a), which were separated chromatographically. Deacetylation of 4a or 5a afforded cyclised tetrols, tosylation of which in admixture resulted in 1-deoxy-1-(indol-3-yl)-3,5-di-O-tosyl-alpha-L-sorbopyranose (12a) and 1-deoxy-1-(indol-3-yl)-4,5-di-O-tosyl-alpha-L-tagatopyranose (13a). Under alkaline conditions 13a readily formed 2-hydroxy-4-hydroxymethyl-3-(indol-3-yl)cyclopenten-2-one (15a) in 90% yield. Similar transformations were performed for N-methyl- and N-methoxyindole derivatives.

  8. Domino Knoevenagel condensation/intramolecular aldol cyclization route to diverse indolizines with densely functionalized pyridine units.

    PubMed

    Kim, Myungock; Jung, Youngeun; Kim, Ikyon

    2013-10-18

    A highly efficient [4 + 2] annulation route to polysubstituted indolizines is described employing a domino Knoevenagel condensation/intramolecular aldol cyclization process as a key step. Construction of pyridine rings in indolizine skeleton was rapidly achieved from several pyrrole-2-carboxaldehydes in good to excellent yields, leading to indolizines with various substituents at the 5, 6, and 7 positions depending on the reacting active methylene partners.

  9. Indolent Wegener's granulomatosis.

    PubMed Central

    Macfarlane, D G; Bourne, J T; Dieppe, P A; Easty, D L

    1983-01-01

    Classical Wegener's granulomatosis is a relentlessly progressive and rapidly fatal disease. A pulmonary 'limited form' is associated with a much better prognosis. We report 3 cases of Wegener's granulomatosis which ran a prolonged indolent course despite major manifestations outside the lower respiratory tract and review the literature on survival. Images PMID:6882035

  10. Rituximab In Indolent Lymphomas

    PubMed Central

    Sousou, Tarek; Friedberg, Jonathan

    2010-01-01

    Indolent Non Hodgkin's lymphoma (NHL) comprises a group of incurable, generally slow growing lymphomas highly responsive to initial therapy with a relapsing and progressive course. Rituximab, an anti CD-20 antibody, has had a large impact on treatment of indolent NHL. Its effectiveness as a single agent and in conjunction with known chemotherapy regimens has made it a standard of care in the treatment of NHL. Analysis of data obtained from NHL clinical trials as well as data from the National Cancer Institute indicates that the overall survival of indolent NHL has improved since the discovery of rituximab. Given its effectiveness and tolerability, it is currently being investigated as a maintenance agent with encouraging results. This review summarizes several landmark trials utilizing rituximab as a single agent and in combination with chemotherapy for treatment of NHL. In addition, a review of the studied rituximab maintenance dosing schedules and its impact on NHL will also be presented. Overall, rituximab has changed the landscape for treatment of indolent NHL however additional research is necessary to identify the optimal dosing schedule as well as patients most likely to respond to prolonged rituximab therapy. PMID:20350660

  11. Synthesis of 5-alkylated barbituric acids and 3-alkylated indoles via microwave-assisted three-component reactions in solvent-free conditions using Hantzsch 1,4-dihydropyridines as reducing agents.

    PubMed

    Baruah, Biswajita; Seetham Naidu, P; Borah, Pallabi; Bhuyan, Pulak J

    2012-05-01

    Reaction of barbituric acids with aldehydes and dihydropyridines in one pot under microwave (MW) irradiation in the absence of solvent, affords 55–82% of the 5-benzylated barbituric acids. Use of alkyl nitriles or barbituric acids with indole-3-aldehyde and dihydropyridine (DHP) afforded 3-alkylated indoles in 57–76 % yield. In each case DHPs are converted to pyridines.

  12. BRIEF COMMUNICATIONS: Picosecond spectroscopy of pyrrol pigments

    NASA Astrophysics Data System (ADS)

    Lippitsch, M. E.; Leitner, A.; Riegler, M.; Aussenegg, F. R.

    1982-05-01

    Picosecond fluorescence and absorption spectroscopy methods were used to study pyrromethenone, pyrromethene, and biliverdin. These methods made it possible to determine some details of the kinetics of various relaxation mechanisms. The results obtained provided a better understanding of the biological action of pyrrol pigments.

  13. Flexible supercapacitor based on electrochemically synthesized pyrrole formyl pyrrole copolymer coated on carbon microfibers

    NASA Astrophysics Data System (ADS)

    Gholami, Mehrdad; Moozarm Nia, Pooria; Narimani, Leila; Sokhakian, Mehran; Alias, Yatimah

    2016-08-01

    The main objective of this work is to prepare a flexible supercapacitor using electrochemically synthesized pyrrole formyl pyrrole copolymer P(Py-co-FPy) coated on the carbon microfibers. Due to difficulties of working with carbon microfibers, glassy carbon was used to find out optimized conditions by varying mole ratio of pyrrole and formyl pyrrole monomers on the capacitance value. The prepared electrodes were characterized using Fourier transform infrared spectroscopy (FT-IR), field emission scanning electron microscope (FESEM), Brunauer-Emmett-Teller (BET) analysis, cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). Then the X-ray photoelectron spectroscopy (XPS) was used to characterize the optimized electrode. The specific capacitance is calculated using cyclic voltammetry, charge/discharge method, and impedance spectroscopy. The charge/discharge study reveals that the best specific capacitance is estimated to be 220.3 mF cm-2 for equal mole fraction of pyrrole and formyl pyrrole Py (0.1)-FP (0.1) at discharge current of 3 × 10-4 A. This optimized electrode keeps about 92% of its capacitance value in high current of discharging. The specific capacitances calculated by all the mentioned methods are in agreement with each other. Finally, the found optimized conditions were successfully applied to produce a flexible supercapacitor on the surface of carbon microfibers.

  14. Electrochemical polypyrrole formation from pyrrole 'adlayer'.

    PubMed

    Plausinaitis, Deivis; Sinkevicius, Linas; Mikoliunaite, Lina; Plausinaitiene, Valentina; Ramanaviciene, Almira; Ramanavicius, Arunas

    2017-01-04

    In this research study, we investigated the morphology of polypyrrole nanostructures, which were formed during the electrochemical deposition of conducting polymer. An electrochemical quartz crystal microbalance (EQCM) cell equipped with a flow-through system was employed to exchange solutions of different compositions within the EQCM cell. When bare PBS buffer in the EQCM cell was exchanged with PBS buffer with pyrrole we observed a distinct increase in the resonance frequency Δf. This change in the resonance frequency and electrical capacitance, which was calculated from electrochemical impedance spectroscopy (EIS) data, illustrate that pyrrole on the surface of the gold electrode formed an adsorbed layer (adlayer). The formation of a pyrrole adlayer before the potential pulse that induced polymerization was investigated by QCM-based measurements. The electrochemical polymerization of this adlayer was induced by a single potential pulse and a nanostructured layer, which consisted of adsorbed polypyrrole (Ppy) nanoparticles with a diameter of 50 nm, was formed. QCM and EIS data revealed that by the next cycle of the electrochemical formation of Ppy, which was investigated after flow-through-based exchange of solutions, the initially formed Ppy surface was covered by the adlayer of pyrrole. This adlayer was desorbed when pyrrole was removed from the solution. When electrochemical polymerization was performed using 50 potential pulses, a Ppy layer, which had more complex morphology, was formed on the EQCM crystal. Scanning electron microscopy showed that the conductivity of this layer was unequally distributed. We observed that the polypyrrole layer formed by electrochemical deposition, which was performed using potential pulses, was formed out of aggregated spherical Ppy particles with a diameter of 50 nm.

  15. Proton-transfer mediated quenching of pyrene/indole charge-transfer states in isooctane solutions.

    PubMed

    Altamirano, Marcela S; Bohorquez, María del Valle; Previtali, Carlos M; Chesta, Carlos A

    2008-01-31

    The fluorescence quenching of pyrene (Py) by a series of N-methyl and N-H substituted indoles was studied in isooctane at 298 K. The fluorescence quenching rate constants were evaluated by mean of steady-state and time-resolved measurements. In all cases, the quenching process involves a charge-transfer (CT) mechanism. The I(o)/I and tau(o)/tau Stern-Volmer plots obtained for the N-H indoles show a very unusual upward deviation with increasing concentration of the quenchers. This behavior is attributed to the self-quenching of the CT intermediates by the free indoles in solution. The efficiency of quenching of the polyaromatic by the N-H indoles increases abruptly in the presence of small amount of added pyridine (or propanol). A detailed analysis of the experimental data obtained in the presence of pyridine provides unambiguous evidence that the self-quenching process involves proton transfer from the CT states to indoles.

  16. 2-(1H-Indol-3-yl)acetohydrazide

    PubMed Central

    Sidra, Lala Rukh; Khan, Islam Ullah; Yar, Muhammad; Simpson, Jim

    2012-01-01

    In the title compound C10H11N3O, the mean plane of the indole ring system (r.m.s. deviation 0.0131 Å) subtends a dihedral angle of 87.27 (5)° to the almost planar acetohydrazide substituent (r.m.s. deviation 0.0291 Å). In the crystal, bifurcated N—H⋯(O,N) and N—H⋯N hydrogen bonds involving the pyrrole N–H grouping combine to form zigzag chains along a. Additional N—H⋯O contacts from the hydrazide N–H group augmented by C—H⋯π inter­actions link the mol­ecules into chains along the a axis. The overall effect of these contacts is a three-dimensional network structure with mol­ecules stacked along the b-axis direction. PMID:23284462

  17. 2-(1H-Indol-3-yl)acetohydrazide.

    PubMed

    Sidra, Lala Rukh; Khan, Islam Ullah; Yar, Muhammad; Simpson, Jim

    2012-11-01

    In the title compound C(10)H(11)N(3)O, the mean plane of the indole ring system (r.m.s. deviation 0.0131 Å) subtends a dihedral angle of 87.27 (5)° to the almost planar acetohydrazide substituent (r.m.s. deviation 0.0291 Å). In the crystal, bifurcated N-H⋯(O,N) and N-H⋯N hydrogen bonds involving the pyrrole N-H grouping combine to form zigzag chains along a. Additional N-H⋯O contacts from the hydrazide N-H group augmented by C-H⋯π inter-actions link the mol-ecules into chains along the a axis. The overall effect of these contacts is a three-dimensional network structure with mol-ecules stacked along the b-axis direction.

  18. Relationship between structures of substituted indolic compounds and their degradation by marine anaerobic microorganisms.

    PubMed

    Gu, Ji-Dong; Fan, Yanzhen; Shi, Hanchang

    2002-01-01

    Degradation of selected indolic compounds including indole, 1-methylindole, 2-methylindole, and 3-methylindole was assessed under methanogenic and sulfate-reducing conditions using the serum-bottle anaerobic technique and marine sediment from Victoria Harbour, Hong Kong as an inoculum. Our results showed that indole degradation was achieved in 28 days by a methanogenic consortium and 35 days by a sulfate-reducing consortium. During degradation under both conditions, two intermediates were isolated, purified and identified as oxindole and isatin (indole-2,3-dione) suggesting that both methanogenic and sulfate-reducing bacteria use an identical degradation pathway. Degradation processes followed two steps of oxidation accomplished by hydroxylation and then dehydrogenation at 2- and then 3-position sequentially prior to the cleavage of the pyrrole ring between 2- and 3-positions. However, none of 1-methylindole or 2-methylindole was degraded under any conditions. 3-Methylindole (3-methyl-1H-indole, skatole) was transformed under methanogenic conditions and mineralized only under sulfate-reducing conditions. It is clear that methyl substitution on 1- or 2-position inhibits the initial attack by hydroxylation enzymes making them more persistent in the environment and posing longer toxic impact.

  19. Vibrational Overtone Spectroscopy of Pyrrole and Pyrrolidine

    DTIC Science & Technology

    1991-05-23

    general pattern is a strong peak accompanied by two or three weaker peaks to lower energy. For instance, the 13,305 cm-I band in pyrrole has three weaker...Orza, J.M. Anales de Quimica 1984, 80, 59. 29. Navarro, R.; Orza, J.M. Anales de Quimica 1982, 79, 557. 30. Xie, Y; Fan, K.; Boggs,J., Molec. Phys

  20. Self-assembly of dimeric tetraurea calix[4]pyrrole capsules

    PubMed Central

    Ballester, Pablo; Gil-Ramírez, Guzmán

    2009-01-01

    Calix[4]pyrroles having extended aromatic cavities have been functionalized with 4 ureas in the para position of their meso phenyl substituents. This elaboration of the upper rim was completed in 2 synthetic steps starting from the α,α,α,α-tetranitro isomer of the calix[4]pyrrole obtained in the acid catalyzed condensation of p-nitrophenyl methyl ketone and pyrrole. In dichloromethane solution and in the presence of 4,4′-bipyridine N-N′-dioxide the tetraurea calix[4]pyrrole dimerizes reversibly forming a cyclic array of 16 hydrogen bonds and encapsulating 1 molecule of bis-N-oxide. The encapsulated guest is bound in the cavity by hydrogen bonding to the 2 endohedral calix[4]pyrrole centers. Further evidence for dimerization of the tetraurea calix[4]pyrroles is provided by 1H-NMR experiments and by the formation of mixed capsules. PMID:19261848

  1. Polyvinyl pyridine microspheres

    NASA Technical Reports Server (NTRS)

    Rembaum, Alan (Inventor); Gupta, Amitava (Inventor); Volksen, Willi (Inventor)

    1980-01-01

    Microspheres are produced by cobalt gamma radiation initiated polymerization of a dilute aqueous vinyl pyridine solution. Addition of cross-linking agent provides higher surface area beads. Addition of monomers such as hydroxyethylmethacrylate acrylamide or methacrylamide increases hydrophilic properties and surface area of the beads. High surface area catalytic supports are formed in the presence of controlled pore glass substrate.

  2. Polyvinyl pyridine microspheres

    NASA Technical Reports Server (NTRS)

    Rembaum, Alan (Inventor); Gupta, Amitava (Inventor); Volksen, Willi (Inventor)

    1979-01-01

    Microspheres are produced by cobalt gamma radiation initiated polymerization of a dilute aqueous vinyl pyridine solution. Addition of cross-linking agent provides higher surface area beads. Addition of monomers such as hydroxyethylmethacrylate acrylamide or methacrylamide increases hydrophilic properties and surface area of the beads. High surface area catalytic supports are formed in the presence of controlled pore glass substrate.

  3. Probing the hydrolytic reactivity of 2-difluoromethyl pyrroles.

    PubMed

    Melanson, Jennifer A; Figliola, Carlotta; Smithen, Deborah A; Kajetanowicz, Aleksandra K; Thompson, Alison

    2016-12-20

    α-Difluoromethyl pyrroles were found to be stable while N-protected with an electron-withdrawing group. Due to the propensity of pyrroles to access azafulvenium-like intermediates, the C-F bonds of an α-difluoromethyl substituent are labile under hydrolytic conditions. The presence of certain electron-withdrawing substituents about the pyrrolic ring can accelerate this process, as determined through a kinetic comparison of the deprotection and subsequent hydrolysis reactions of N-protected β-aryl α-difluoromethyl pyrroles.

  4. Rh2 (S-biTISP)2-Catalyzed Asymmetric Functionalization of Indoles and Pyrroles with Vinylcarbenoids

    PubMed Central

    Lian, Yajing; Davies, Huw M. L.

    2012-01-01

    Asymmetric functionalization of N-heterocycles by vinylcarbenoids in the presence of catalytic amounts of Rh2 (S-biTISP)2 has been successfully developed. This bridged dirhodium catalyst not only selectively enforces the reaction to occur at the vinylogous position of the carbenoid, but also, affords high levels of asymmetric induction. PMID:22452332

  5. Photoejection of electrons from pyrrole into an aqueous environment: ab initio results on pyrrole-water clusters

    NASA Astrophysics Data System (ADS)

    Sobolewski, Andrzej L.; Domcke, Wolfgang

    2000-05-01

    Ab initio (RHF, CASSCF and CASPT2) calculations in the ground and lowest excited singlet states have been performed on pyrrole and pyrrole-water clusters. Full geometry optimization in the 1πσ ∗ state, which is energetically accessible from the optically allowed 1ππ ∗ state, reveals the flow of the electronic charge from pyrrole towards the water molecules, i.e., the formation of a charge transfer-to-solvent state. The computational results indicate that pyrrole-water clusters are good models for the investigation of the mechanistic details of the electron solvation process occurring upon ultraviolet photoexcitation of organic chromophores in liquid water.

  6. 1-Ethyl-2-phenyl-3-[2-(tri-methyl-sil-yl)ethyn-yl]-1H-indole.

    PubMed

    Baglai, Iaroslav; Maraval, Valérie; Duhayon, Carine; Chauvin, Remi

    2013-06-01

    The title compound, C21H23NSi, was synthesized by Sonogashira-type reaction of 1-ethyl-3-iodo-2-phenyl-1H-indole with tri-methyl-silyl-acetyl-ene. The indole ring system is nearly planar [maximum atomic deviation = 0.0244 (15) Å] and is oriented at a dihedral angle of 51.48 (4)° with respect to the phenyl ring. The supramolecular aggregation is completed by weak C-H⋯π inter-actions of the methylene and phenyl groups with the benzene and pyrrole rings of the indole ring system. The methyl groups of the tri-methyl-silyl unit are equally disordered over two sets of sites.

  7. Morphology and electrical properties of electrochemically synthesized pyrrole-formyl pyrrole copolymer

    NASA Astrophysics Data System (ADS)

    Gholami, Mehrdad; Nia, Pooria Moozarm; Alias, Yatimah

    2015-12-01

    A direct electrochemical copolymerization of pyrrole-formyl pyrrole (Py-co-FPy) was carried out by oxidative copolymerization of formyl pyrrole and pyrrole in LiClO4 aqueous solution through galvanostatic method. The (Py-co-FPy) copolymer was characterized using Fourier-transform infrared spectroscopy (FT-IR), field emission scanning electron microscope (FESEM), energy-filtering transmission electron microscope (EFTEM), thermal gravimetric analysis (TGA), X-ray photoelectron spectroscopy (XPS), cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). The FESEM images showed that the synthesized copolymer had a hollow whelk-like helixes structure, which justifies the enhancement of charge transportation through the copolymer film. Cyclic voltammetry studies revealed that the electrocatalytic activity of synthesized copolymer has improved and the surface coverage in copolymer enhanced 1.6 times compared to polypyrrole alone. Besides, (Py-co-FPy) copolymer showed 2.5 times lower electrochemical charge transfer resistance (Rct) value in impedance spectroscopy. Therefore, this copolymer has a strong potential to be used in several applications such as sensor applications.

  8. Synthesis and Evaluation of Cytotoxic Activity of Some Pyrroles and Fused Pyrroles.

    PubMed

    Fatahala, Samar S; Mohamed, Mosaad S; Youns, Mahmoud; Abd-El Hameed, Rania H

    2017-01-01

    Pyrrole derivatives represent a very interesting class as biologically active compounds. The objective of our study was to investigate the cytotoxic and apoptotic effects and antioxidant activity of the newly synthesized pyrrole derivatives. A series of novel pyrroles and fused pyrroles (tetrahydroindoles, pyrrolopyrimidines, pyrrolopyridines and pyrrolotriazines) were synthesized and characterized using IR, 1H NMR, 13C NMR, MS and elemental analysis techniques. The antiproliferative activity of our synthesized compounds and their modulatory effect apoptotic pathway were investigated. The effect on cellular proliferation and viability was monitored by resazurin assay. Apoptotic effect was evaluated by caspase glo 3/7 assay. Synthesized compounds are then tested for their anticancer activities against three different cell lines representing three different tumor types, namely; the HepG-2 (Human hepatocellular liver carcinoma cell line), the human MCF-7 cell line (breast cancer) and the pancreatic resistant Panc-1 cells. Compounds Ia-e, IIe, and IXc, d showed a promising anti-cancer activity on all tested cell lines. Antioxidant and wound healing invasion assays were examined for promising anticancer candidate compounds. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  9. CuO/SiO2 as a simple, effective and recoverable catalyst for alkylation of indole derivatives with diazo compounds.

    PubMed

    Fraile, José M; Le Jeune, Karel; Mayoral, José A; Ravasio, Nicoletta; Zaccheria, Federica

    2013-07-14

    The purely inorganic copper oxide on silica catalyzes the reaction of methyl phenyldiazoacetate with N-methyl indole under mild reaction conditions, giving the alkylation (formally a C-H insertion) in position 3, and the catalyst can be recovered and reused at least in 5 consecutive runs with only minor loss in activity. The scope of the reaction includes various diazo compounds and indole or pyrrole derivatives leading to alkylation or cyclopropanation depending on the heterocycle structure. An alternative mechanism, without reduction of Cu(II) to Cu(I), is proposed on the basis of the obtained results.

  10. Synthesis of Propionamide Pyridine and Pyridine N-oxide Ligands

    SciTech Connect

    Binyamin, Iris; Pailloux, Sylvie; Hay, Benjamin P; Rapko, Brian M; Duesler, Eileen N; Paine, Robert T

    2007-02-01

    A new set of pyridine and pyridine N-oxides functionalized with N,N-dimethylpropionamide pendant groups in the 2- and 2,6-positions have been prepared from the combination of 2-chloromethylpyridine and 2,6-bis(chloromethyl) pyridine with -lithio N,N-dimethyl acetamide. The coordination interaction between 2-(N,N-dimethylpropionamide) pyridine N-oxide (10) and Tb(NO3)3 has been unambiguously defined via single crystal X-ray diffraction analysis of Tb(10)(NO3)3(H2O). Battelle operates PNNL for the USDOE

  11. Substituent effects on the structural features and nonlinear optical properties of the organic alkalide Li+ (calix[4]pyrrole)Li-.

    PubMed

    Sun, Wei-Ming; Wu, Di; Li, Ying; Li, Zhi-Ru

    2013-02-04

    The effects of substituents on the structure, character, and nonlinear optical (NLO) properties of the organic alkalide Li(+) (calix[4]pyrrole)Li(-) were studied by density functional theory. Natural bond orbital analysis and vertical ionization energies reveal that electron-donating substituents strengthen the alkalide character of Li(+) (calix[4]pyrrole)Li(-) and that they are beneficial for a larger first hyperpolarizability (β(0) ) value. However, electron-withdrawing substituents have the opposite effect. The dependence of the NLO properties on the number of substituents and their relative position was detected in multisubstituted Li(+) (calix[4]pyrrole)Li(-) compounds. For both the amino- and methyl-substituted derivatives, the polarizabilities and the first hyperpolarizabilities increase as more pyrrole β-H atoms are substituted. Moreover, distribution of the substituents so that they are as far away from each other as possible resulted in an increase in the β(0) value. The new knowledge obtained in this study may provide an effective approach to enhance the NLO responses of alkalides by employing pyrrole derivatives as complexants.

  12. Rapid determination of pyridine derivatives by dispersive liquid-liquid microextraction coupled with gas chromatography/gas sensor based on nanostructured conducting polypyrrole.

    PubMed

    Pirsa, Sajad; Alizadeh, Naader

    2011-12-15

    Polypyrrole (PPy) gas sensor has been prepared by polymerization of pyrrole on surfaces of commercial polymer fibers in the presence of an oxidizing agent. The sensing behavior of PPy gas sensor was investigated in the presence of pyridine derivatives. The resistive responses of the PPy gas sensor to pyridine derivatives were in the order of quinoline>pyridine>4-methyl pyridine and 2-methyl pyridine. The PPy gas sensor was used as gas chromatography (GC) detector and exhibited linear responses to pyridine derivatives in the ranges 40-4,000 ng. Dispersive liquid-liquid microextraction (DLLME) combined with GC/PPy gas sensor has been developed for simultaneous determination of pyridine derivatives and quinoline. The purposed method was used for determination of pyridine derivatives from cigarette smoke. The GC runs were completed in 4 min. The reproducibility of this method is suitable and good standard deviations were obtained. RSD value is less than 10% for all analytes. Copyright © 2011 Elsevier B.V. All rights reserved.

  13. 2-[(1H-Pyrrol-2-yl)meth­yl]-1H-pyrrole

    PubMed Central

    Kim, Chong-Hyeak; Jeon, Yea-Sel; Lynch, Vincent; Sessler, Jonathan L.; Hwang, Kwang-Jin

    2013-01-01

    In the title compound, C9H10N2, the two pyrrole ring planes are twisted by a dihedral angle of 69.07 (16)° and the C—C—C methane angle is 115.1 (2)°. In the crystal, mol­ecules are connected into layers in the bc plane by N—H⋯π inter­actions. PMID:24454123

  14. Hydroquinone–pyrrole dyads with varied linkers

    PubMed Central

    Huang, Hao; Karlsson, Christoffer; Strømme, Maria; Sjödin, Martin

    2016-01-01

    Summary A series of pyrroles functionalized in the 3-position with p-dimethoxybenzene via various linkers (CH2, CH2CH2, CH=CH, C≡C) has been synthesized. Their electronic properties have been deduced from 1H NMR, 13C NMR, and UV–vis spectra to detect possible interactions between the two aromatic subunits. The extent of conjugation between the subunits is largely controlled by the nature of the linker, with the largest conjugation found with the trans-ethene linker and the weakest with the aliphatic linkers. DFT calculations revealed substantial changes in the HOMO–LUMO gap that correlated with the extent of conjugation found experimentally. The results of this work are expected to open up for use of the investigated compounds as components of redox-active materials in sustainable, organic electrical energy storage devices. PMID:26877811

  15. Parallel interactions at large horizontal displacement in pyridine-pyridine and benzene-pyridine dimers.

    PubMed

    Ninković, Dragan B; Andrić, Jelena M; Zarić, Snežana D

    2013-01-14

    A study of crystal structures from the Cambridge Structural Database (CSD) and DFT calculations reveals that parallel pyridine-pyridine and benzene-pyridine interactions at large horizontal displacements (offsets) can be important, similar to parallel benzene-benzene interactions. In the crystal structures from the CSD preferred parallel pyridine-pyridine interactions were observed at a large horizontal displacement (4.0-6.0 Å) and not at an offset of 1.5 Å with the lowest calculated energy. The calculated interaction energies for pyridine-pyridine and benzene-pyridine dimers at a large offset (4.5 Å) are about 2.2 and 2.1 kcal mol(-1), respectively. Substantial attraction at large offset values is a consequence of the balance between repulsion and dispersion. That is, dispersion at large offsets is reduced, however, repulsion is also reduced at large offsets, resulting in attractive interactions. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. Palladium(0)-Catalyzed Heteroarylation of 2- and 3-Indolylzinc Derivatives. An Efficient General Method for the Preparation of (2-Pyridyl)indoles and Their Application to Indole Alkaloid Synthesis.

    PubMed

    Amat, Mercedes; Hadida, Sabine; Pshenichnyi, Grigorii; Bosch, Joan

    1997-05-16

    Palladium(0)-catalyzed coupling of (1-(benzenesulfonyl)-2-indolyl)zinc chloride (1) and (1-(tert-butyldimethylsilyl)-3-indolyl)zinc chloride (6) with diversely substituted (alkyl, methoxy, methoxycarbonyl, nitro, hydroxy) 2-halopyridines gives the corresponding 2- and 3-(2-pyridyl)indoles [4 and 7 (or 8), respectively] in excellent yields. A series of other 3-(heteroaryl)indoles (pyrazinyl, furyl, thienyl, indolyl) have been similarly prepared from 6. The potential of some of these (2-pyridyl)indoles in alkaloid synthesis is demonstrated. Thus, from 2-(2-pyridyl)indole 4b, a new synthetic entry to the indolo[2,3-a]quinolizidine system, involving stereoselective hydrogenation of the pyridine ring with subsequent electrophilic cyclization upon the indole 3-position from an appropriately N(b)-substituted 2-(2-piperidyl)indole, is reported. For this purpose, Pummerer cyclizations have been extensively studied. Whereas the indole-unprotected sulfoxide 17 gives the corresponding indoloquinolizidine 19 in low yield and mainly undergoes an abnormal Pummerer cyclization that ultimately leads to sulfide 18, the N(a)-protected sulfoxides 24a and 24b afford the respective indoloquinolizidines 25a,b in 70% yield. On the other hand, the conversion of 3-(2-pyridyl)indole 8k into tetracyclic ketone 35 by stereoselective hydrogenation, followed by cyclization of the resulting all-cis-3-(2-piperidyl)indole 34, represents a formal synthesis of Strychnos alkaloids with the strychnan skeletal type (tubifoline, tubifolidine, 19,20-dihydroakuammicine). A similar conversion of 8j into nordasycarpidone constitutes a formal synthesis of the alkaloids of the uleine group. Reduction of nordasycarpidone leads to tetracycle 37, an advanced intermediate in a previous synthesis of tubotaiwine, a Strychnos alkaloid with the aspidospermatan skeletal type. Finally, piperidylindole 34 was transformed into tetracycle 41, an ABDE substructure of akuammiline alkaloids, by a sequence involving the

  17. Pyridine Aggregation in Helium Nanodroplets

    NASA Astrophysics Data System (ADS)

    Nieto, Pablo; Poerschke, Torsten; Habig, Daniel; Schwaab, Gerhard; Havenith, Martina

    2012-06-01

    Pyridine crystals show the unusual property of isotopic polymorphism. Experimentally it has been observed that deuterated pyridine crystals exist in two phases while non-deuterated pyridine does not show a phase transition. Therefore, although isotopic substitution is the smallest possible modification of a molecule it greatly affects the stability of pyridine crystals. A possible experimental approach in order to understand this striking effect might be the study of pyridine aggregation for small clusters. By embedding the clusters in helium nanodroplets the aggregates can be stabilized and studied by means of Infrared Depletion Spectroscopy. Pyridine oligomers were investigated in the C-H asymmetric vibration region (2980-3100 cm-1) using this experimental technique. The number of molecules for the clusters responsibles for each band were determined by means of pick-up curves as well as mass sensitive depletion spectra. Furthermore, the intensity dependence of the different bands on applying a dc electric field was studied. The assignment of the different structures for pyridine clusters on the basis of these measurements were also carried out. S. Crawford et al., Angew. Chem. Int. Ed., 48, 755 (2009).

  18. The harmonic force field and vibrational spectra of pyrrole

    NASA Astrophysics Data System (ADS)

    Xie, Yaoming; Fan, Kangnian; Boggs, James E.

    The complete harmonic vibrational force field of pyrrole has been calculated by the ab initio gradient method at the Hartree-Fock level using the 4-21 basis set. The force field was then scaled with a set of six factors transferred from benzene, and the vibrational spectrum of pyrrole was calculated. This a priori prediction, made with no reference to observations on pyrrole, agreed with the known experimental fundamental frequencies with a mean deviation of 12 cm-1 for in-plane modes and 20 cm-1 for out-of-plane modes except for the NH wagging and NH stretch. A new set of ten scale factors was next obtained by direct fitting of the computed force field to the observed pyrrole spectrum, producing the best force field obtainable by combined use of the theoretical and experimental information. This force field reproduced the entire pyrrole spectrum with mean deviations of 4·2 cm-1 (in-plane) and 5·9 cm-1 (out-of-plane). The spectra of three deuterated forms of pyrrole were also computed. Infrared absorption intensities were calculated and proved very useful in examining assignments of the two ring torsional modes and the CH stretching modes.

  19. Chemistry and Biology of the Pyrrole-Imidazole Alkaloids.

    PubMed

    Lindel, Thomas

    2017-01-01

    More than a decade after our last review on the chemistry of the pyrrole-imidazole alkaloids, it was time to analyze once more the developments in that field. The comprehensive article focusses on the total syntheses of pyrrole-imidazole alkaloids that have appeared since 2005. The classic monomeric pyrrole-imidazole alkaloids have all been synthesized, sometimes primarily to demonstrate the usefulness of a new method, as in the case of the related molecules agelastatin A and cyclooroidin with more than 15 syntheses altogether. The phakellin skeleton has been made more than 10 times, too, with a focus on the target structure itself. Thus, some of the pyrrole-imidazole alkaloids are now available in gram amounts, and the supply problem has been solved. The total synthesis of the dimeric pyrrole-imidazole alkaloids is still mostly in its pioneering phase with two routes to palau'amine and massadine discovered and three routes to the axinellamines and ageliferin. In addition, the review summarizes recent discoveries regarding the biological activity of the pyrrole-imidazole alkaloids. Regarding the biosynthesis of sceptrin, a pathway is proposed that starts from nagelamide I and proceeds via two electrocyclizations and reduction.

  20. Chemiluminescence of indole and its derivatives

    NASA Astrophysics Data System (ADS)

    Vasil'ev, Rostislav F.; Trofimov, A. V.; Tsaplev, Yuri B.

    2010-02-01

    The results of studies on chemiluminescence of indole and its derivatives are critically analyzed. It is shown that chemical transformations of indoles lead, depending on the structure and experimental conditions, to various electronically excited products and emission of light. Many reactions considered are used as a basis for highly sensitive methods for detection of indoles in biology, medicine, ecology and forensics.

  1. Basicity of pyridine and some substituted pyridines in ionic liquids.

    PubMed

    Angelini, Guido; De Maria, Paolo; Chiappe, Cinzia; Fontana, Antonella; Pierini, Marco; Siani, Gabriella

    2010-06-04

    The equilibrium constants for ion pair formation of some pyridines have been evaluated by spectrophotometric titration with trifluoroacetic acid in different ionic liquids. The basicity order is the same in ionic liquids and in water. The substituent effect on the equilibrium constant has been discussed in terms of the Hammett equation. Pyridine basicity appears to be less sensitive to the substituent effect in ionic liquids than in water.

  2. Inhibition of KRAS codon 12 mutants using a novel DNA-alkylating pyrrole-imidazole polyamide conjugate.

    PubMed

    Hiraoka, Kiriko; Inoue, Takahiro; Taylor, Rhys Dylan; Watanabe, Takayoshi; Koshikawa, Nobuko; Yoda, Hiroyuki; Shinohara, Ken-ichi; Takatori, Atsushi; Sugimoto, Hirokazu; Maru, Yoshiaki; Denda, Tadamichi; Fujiwara, Kyoko; Balmain, Allan; Ozaki, Toshinori; Bando, Toshikazu; Sugiyama, Hiroshi; Nagase, Hiroki

    2015-04-27

    Despite extensive efforts to target mutated RAS proteins, anticancer agents capable of selectively killing tumour cells harbouring KRAS mutations have remained unavailable. Here we demonstrate the direct targeting of KRAS mutant DNA using a synthetic alkylating agent (pyrrole-imidazole polyamide indole-seco-CBI conjugate; KR12) that selectively recognizes oncogenic codon 12 KRAS mutations. KR12 alkylates adenine N3 at the target sequence, causing strand cleavage and growth suppression in human colon cancer cells with G12D or G12V mutations, thus inducing senescence and apoptosis. In xenograft models, KR12 infusions induce significant tumour growth suppression, with low host toxicity in KRAS-mutated but not wild-type tumours. This newly developed approach may be applicable to the targeting of other mutant driver oncogenes in human tumours.

  3. 1-Ethyl-2-phenyl-3-[2-(tri­methyl­sil­yl)ethyn­yl]-1H-indole

    PubMed Central

    Baglai, Iaroslav; Maraval, Valérie; Duhayon, Carine; Chauvin, Remi

    2013-01-01

    The title compound, C21H23NSi, was synthesized by Sonogashira-type reaction of 1-ethyl-3-iodo-2-phenyl-1H-indole with tri­methyl­silyl­acetyl­ene. The indole ring system is nearly planar [maximum atomic deviation = 0.0244 (15) Å] and is oriented at a dihedral angle of 51.48 (4)° with respect to the phenyl ring. The supramolecular aggregation is completed by weak C—H⋯π inter­actions of the methylene and phenyl groups with the benzene and pyrrole rings of the indole ring system. The methyl groups of the tri­methyl­silyl unit are equally disordered over two sets of sites. PMID:23795091

  4. Photofragment slice imaging studies of pyrrole and the Xe⋯pyrrole cluster

    NASA Astrophysics Data System (ADS)

    Rubio-Lago, L.; Zaouris, D.; Sakellariou, Y.; Sofikitis, D.; Kitsopoulos, T. N.; Wang, F.; Yang, X.; Cronin, B.; Devine, A. L.; King, G. A.; Nix, M. G. D.; Ashfold, M. N. R.; Xantheas, S. S.

    2007-08-01

    The photolysis of pyrrole has been studied in a molecular beam at wavelengths of 250, 240, and 193.3nm, using two different carrier gases, He and Xe. A broad bimodal distribution of H-atom fragment velocities has been observed at all wavelengths. Near threshold at both 240 and 250nm, sharp features have been observed in the fast part of the H-atom distribution. Under appropriate molecular beam conditions, the entire H-atom lo iable index in order to predict the changes in the highest occupied molecular orbital eigenvalue due to doping.

  5. Molecular dynamics simulation of pyridine

    NASA Astrophysics Data System (ADS)

    Trumpakaj, Zygmunt; Linde, Bogumił

    2015-04-01

    Molecular Dynamics (MD) simulations are used for the investigation of molecular motions in pyridine in the temperature range 20-480 K under normal pressure. The results obtained are analyzed within the frame of the Mori Zwanzig memory function formalism. An analytical approximation of the first memory function K(t) is applied to predict some dependences on temperature. Experimental results of the Rayleigh scattering of depolarized light from liquid pyridine are used as the main base for the comparison.

  6. Spot indole test: evaluation of four reagents.

    PubMed Central

    Miller, J M; Wright, J W

    1982-01-01

    Kovacs indole reagent, p-dimethylaminobenzaldehyde, Ehrlich indole reagent and p-dimethylaminocinnamaldehyde were used as spot indole reagents to test 359 strains of gram-negative rods growing on 5% sheep blood agar, Trypticase soy agar (BBL Microbiology Systems), and MacConkey agar. The p-dimethylaminocinnamaldehyde reagent was the most sensitive of those tested and provided results that were easiest to interpret. The p-dimethylaminocinnamaldehyde reagent was able to detect providencia alcalifaciens indole production because of the red-violet color unique to that organism. All reagents tested were accurate in detecting indole produced by members of the Enterobacteriaceae family, with the exception of P. alcalifaciens. PMID:7040458

  7. Electrogenerated poly(pyrrole-lactosyl) and poly(pyrrole-3'-sialyllactosyl) interfaces: towards the impedimetric detection of lectins

    NASA Astrophysics Data System (ADS)

    Gondran, Chantal; Dubois, Marie-Pierre; Fort, Sebastien; Cosnier, Serge

    2013-07-01

    This paper reports on the impedimetric transduction of binding reaction between polymerized saccharides and target lectins. The controlled potential electro-oxidation of pyrrole-lactosyl and pyrrole-3’-sialyllactosyl at 0.95 V vs Ag/AgCl, provides thin and reproducible poly(pyrrole-saccharide) films. The affinity binding of two lectins: Arachis hypogaea, (PNA) and Maackia amurensis (MAA) onto poly(pyrrole-lactosyl) and poly(pyrrole-3’-sialyllactosyl) electrodes, was demonstrated by cyclic voltammetry in presence of ruthenium hexamine and hydroquinone. In addition, rotating disk experiments were carried out to determine the permeability of both polypyrrole films and its evolution after incubating with lectin target. Finally, the possibility of using the poly(pyrrole-lactosyl) or poly(pyrrole-3’-siallyllactosyl) films for the impedimetric transduction of the lectin binding reaction, was investigated with hydroquinone (2×10-3 mol L-1) as a redox probe in phosphate buffer. The resuting impedance spectra were interpreted and modeled as an equivalent circuit indicating that charge transfer resistance (Rct) and relaxation frequency (f°) parameters are sensitive to the lectin binding. Rct increases from 77 to 97 Ω cm2 for PNA binding and from 93 to 131 Ω cm2 for MAA binding. In parallel, f° decreases from 276 to 222 Hz for PNA binding and from 223 to 131 Hz for MAA binding. This evolution of both parameters reflects the steric hindrances generated by the immobilised lectins towards the permeation of the redox probe.

  8. Brønsted acid-catalyzed Nazarov cyclization of pyrrole derivatives accelerated by microwave irradiation.

    PubMed

    Bachu, Prabhakar; Akiyama, Takahiko

    2009-07-15

    The Brønsted acid-catalyzed Nazarov cyclization of pyrrole derivatives was developed. Microwave irradiation accelerated the Nazarov cyclization significantly at 40 degrees C to give cyclopenta[b]pyrrole derivatives in excellent yields with high trans selectivity.

  9. Indolent palatal swelling: Catch 22

    PubMed Central

    Sharma, Preeti; Wadhwan, Vijay; Kumar, K. V. Arun; Venkatesh, Arvind; Thapa, Timsy

    2016-01-01

    We present an interesting but intriguing case of an indolent palatal swelling. The lesion was asymptomatic causing little discomfort to the patient and thus was an incidental clinical finding. Provisional diagnosis was a benign, minor salivary gland tumor. Clinical differential diagnoses included benign lymphoepithelial lesion or mucus extravasation phenomenon. Nevertheless, we also considered malignancies such as mucoepidermoid carcinoma, lymphoma, and neoplasm of the maxillary sinus. However, the histopathology revealed a rare clinicopathologic entity prompting immediate treatment of the lesion. PMID:28356700

  10. Synthesis, characterization and computational study on ethyl 4-(3-Furan-2yl-acryloyl)-3,5-dimethyl-1H-pyrrole-2-carboxylate

    NASA Astrophysics Data System (ADS)

    Singh, R. N.; Rawat, Poonam; Sahu, Sangeeta

    2014-11-01

    As part of study on pyrrole derivatives, we have synthesized a pyrrole chalcone derivative: ethyl 4-(3-Furan-2yl-acryloyl)-3,5-dimethyl-1H-pyrrole-2-carboxylate (EFADPC) by aldol condensation of ethyl 3, 5-dimethyl-4-actyl-1H-pyrrole-2-carboxylate with furan-2-carbaldehyde in the presence of strong hydroxyl base as catalyst. The product EFADPC has been confirmed by spectroscopic (FT-IR, 1H NMR, and UV-visible) analyses. Quantum chemical calculation also provides good correlation with experimental data. The molecular electrostatic potential surface (MEP), natural bond orbital interactions (NBO), electronic descriptors, quantum theory of atoms' in molecules (QTAIM) and experimental FT-IR spectrum have been used to predict the sites and nature of interactions which indicate that the dimer formation with multiple interactions through Nsbnd H···O and Csbnd H···O. The vibrational analysis shows red shifts in νNsbnd H and νCdbnd O as result of dimer formation. The binding energy of dimer is calculated as 13.82, 15.24 kcal/mol using DFT, QTAIM analysis, respectively. The result of ellipticity confirms the existence of resonance assisted hydrogen bonds (RAHB) in dimer. The MEP and local reactivity descriptors analyses have been performed and the results indicate that carbonyl carbon and β-carbon of chalcone frame have been prone to nucleophilic attack and lead to large number of heterocyclic compounds such as oxirane, oxazoles, pyrazoles, pyridines, pyrimidines, and pyran.

  11. Versatile functionalization of nanoelectrodes by oligonucleotides via pyrrole electrochemistry.

    PubMed

    Descamps, Emeline; Nguyen, Khoa; Bouchain-Gautier, Christelle; Filoramo, Arianna; Goux-Capes, Laurence; Goffman, Marcello; Bourgoin, Jean-Philippe; Mailley, Pascal; Livache, Thierry

    2010-11-15

    Surface modification at the nanometer scale is a challenge for the future of molecular electronics. In particular, the precise anchoring and electrical addressing of biological scaffolds such as complex DNA nanonetworks is of importance for generating bio-directed assemblies of nano-objects for nanocircuit purposes. Herein, we consider the individual modification of nanoelectrodes with different oligonucleotide sequences by an electrochemically driven co-polymerization process of pyrrole and modified oligonucleotide sequences bearing pyrrole monomers. We demonstrate that this one-step technique presents the advantages of simplicity, localization of surface modification, mechanical, biological and chemical stability of the coatings, and high lateral resolution.

  12. Pyrrolo[3',2':6,7]cyclohepta[1,2-b]pyridines with potent photo-antiproliferative activity.

    PubMed

    Spanò, Virginia; Giallombardo, Daniele; Cilibrasi, Vincenzo; Parrino, Barbara; Carbone, Anna; Montalbano, Alessandra; Frasson, Ilaria; Salvador, Alessia; Richter, Sara N; Doria, Filippo; Freccero, Mauro; Cascioferro, Stella; Diana, Patrizia; Cirrincione, Girolamo; Barraja, Paola

    2017-03-10

    Pyrrolo[3',2':6,7]cyclohepta[1,2-b]pyridines were synthesized as a new class of tricyclic system in which the pyridine ring is annelated to a cycloheptapyrrole scaffold, with the aim of obtaining new photosensitizing agents with improved antiproliferative activity and lower undesired toxic effects. A versatile synthetic pathway was approached, which allowed the isolation of derivatives of the title ring system with a good substitution pattern on the pyrrole moiety. Photobiological studies revealed that the majority of the new compounds showed a potent cytotoxic effect upon photoactivation with light of the proper wavelength, especially when decorated with a 2-ethoxycabonyl group and a N-benzyl substituted moiety, with EC50 values reaching the submicromolar level. The mechanism of action was evaluated.

  13. Crystal structure of (4-cyano­pyridine-κN){5,10,15,20-tetrakis[4-(benzoyloxy)phenyl]porphyrinato-κ4 N}zinc–4-cyano­pyridine (1/1)

    PubMed Central

    Nasri, Soumaya; Amiri, Nesrine; Turowska-Tyrk, Ilona; Daran, Jean-Claude; Nasri, Habib

    2016-01-01

    In the title compound, [Zn(C72H44N4O8)(C6H4N2)]·C6H4N2 or [Zn(TPBP)(4-CNpy]·(4-CNpy) [where TPBP and 4-CNpy are 5,10,15,20-(tetra­phenyl­benzoate)porphyrinate and 4-cyano­pyridine, respectively], the ZnII cation is chelated by four pyrrole-N atoms of the porphyrinate anion and coordinated by a pyridyl-N atom of the 4-CNpy axial ligand in a distorted square-pyramidal geometry. The average Zn—N(pyrrole) bond length is 2.060 (6) Å and the Zn—N(4-CNpy) bond length is 2.159 (2) Å. The zinc cation is displaced by 0.319 (1) Å from the N4C20 mean plane of the porphyrinate anion toward the 4-cyano­pyridine axial ligand. This porphyrinate macrocycle exhibits major saddle and moderate ruffling and doming deformations. In the crystal, the [Zn(TPBP)(4-CNpy)] complex mol­ecules are linked together via weak C—H⋯N, C—H⋯O and C—H⋯π inter­actions, forming supra­molecular channels parallel to the c axis. The non-coordinating 4-cyano­pyridine mol­ecules are located in the channels and linked with the complex mol­ecules, via weak C—H⋯N inter­actions and π-π stacking or via weak C—H⋯O and C—H⋯π inter­actions. The non-coordinating 4-cyano­pyridine mol­ecule is disordered over two positions with an occupancy ratio of 0.666 (4):0.334 (4). PMID:26958379

  14. 27 CFR 21.122 - Pyridine bases.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ....122 Pyridine bases. (a) Alkalinity. One ml of pyridine bases dissolved in 10 ml of water is titrated... 27 Alcohol, Tobacco Products and Firearms 1 2011-04-01 2011-04-01 false Pyridine bases. 21.122... soon disappears. A minimum of 9.5 ml of the acid must be required for the end point. (Congo...

  15. 27 CFR 21.122 - Pyridine bases.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ....122 Pyridine bases. (a) Alkalinity. One ml of pyridine bases dissolved in 10 ml of water is titrated... 27 Alcohol, Tobacco Products and Firearms 1 2013-04-01 2013-04-01 false Pyridine bases. 21.122... soon disappears. A minimum of 9.5 ml of the acid must be required for the end point. (Congo...

  16. 27 CFR 21.122 - Pyridine bases.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2014-04-01 2014-04-01 false Pyridine bases. 21.122....122 Pyridine bases. (a) Alkalinity. One ml of pyridine bases dissolved in 10 ml of water is titrated... soon disappears. A minimum of 9.5 ml of the acid must be required for the end point. (Congo paper...

  17. 27 CFR 21.122 - Pyridine bases.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2012-04-01 2012-04-01 false Pyridine bases. 21.122....122 Pyridine bases. (a) Alkalinity. One ml of pyridine bases dissolved in 10 ml of water is titrated... soon disappears. A minimum of 9.5 ml of the acid must be required for the end point. (Congo paper...

  18. Structure-activity relationships of pyrrole based S-nitrosoglutathione reductase inhibitors: pyrrole regioisomers and propionic acid replacement.

    PubMed

    Sun, Xicheng; Qiu, Jian; Strong, Sarah A; Green, Louis S; Wasley, Jan W F; Colagiovanni, Dorothy B; Mutka, Sarah C; Blonder, Joan P; Stout, Adam M; Richards, Jane P; Chun, Lawrence; Rosenthal, Gary J

    2011-06-15

    S-Nitrosoglutathione reductase (GSNOR) is a member of the alcohol dehydrogenase family (ADH) that regulates the levels of S-nitrosothiols (SNOs) through catabolism of S-nitrosoglutathione (GSNO). GSNO and SNOs are implicated in the pathogenesis of many diseases including those in respiratory, cardiovascular, and gastrointestinal systems. The pyrrole based N6022 was recently identified as a potent, selective, reversible, and efficacious GSNOR inhibitor which is currently undergoing clinical development. We describe here the synthesis and structure-activity relationships (SAR) of novel pyrrole based analogues of N6022 focusing on scaffold modification and propionic acid replacement. We identified equally potent and novel GSNOR inhibitors having pyrrole regioisomers as scaffolds using a structure based approach.

  19. Photoinduced charge separation in indole water clusters

    NASA Astrophysics Data System (ADS)

    Sobolewski, Andrzej L.; Domcke, Wolfgang

    2000-10-01

    Ab initio (RHF, MP2, CASSCF and CASPT2) calculations in the ground and the lowest excited singlet states have been performed for indole-water clusters. The calculations reveal a remarkable role of the lowest 1πσ∗ state in the photochemistry of these systems: indole in the 1πσ∗ state ejects an electron into the aqueous environment, leading to the formation of a charge-separated state. The computational results indicate that indole-water clusters are good models for the investigation of the mechanistic details of the electron solvation process occurring upon UV photoexcitation of indole and tryptophan in liquid water.

  20. Influence of gamma irradiation on polymerization of pyrrole and glucose oxidase immobilization onto poly (pyrrole)/poly (vinyl alcohol) matrix

    NASA Astrophysics Data System (ADS)

    Idris, Sarada; Bakar, Ahmad Ashrif A.; Ratnam, Chantara Thevy; Kamaruddin, Nur Hasiba; Shaari, Sahbudin

    2017-04-01

    This paper describes the immobilization of glucose oxidase, GOx onto polymer matrix comprising of poly(pyrrole), PPy and poly(vinyl alcohol), PVA using gamma irradiation technique. Py/PVA-GOx film was prepared by spreading PVA:GOx, 1:1 solution onto dried pyrrole film and exposed to gamma irradiation from cobalt 60 source at doses ranging from 0 to 60 kGy. The films were subjected to structural and morphological analyses by using Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS), Scanning electron microscope (SEM), Field emission scanning electron microscope (FESEM) and Atomic-force microscopy (AFM) techniques. Similar studies were also made on pristine pyrrole film which served as control. The SEM and FTIR spectra of Py/PVA-GOx film revealed that pyrrole has been successfully polymerized through irradiation-induced reactions. The results on the morphological properties of the samples characterize using FESEM, SEM and AFM further confirmed the occurrence of radiation-induced modification of Py/PVA-GOx film. The FTIR spectra showed the existence of intermolecular interaction between polymer matrix and GOx indicating that GOx had been successfully immobilized onto Ppy/PVA matrix by radiation-induced reactions. Results revealed that radiation induced reactions such as polymerization of pyrrole, crosslinking of PVA, grafting between the adjacent PVA and pyrrole molecules as well as immobilization of GOx onto Ppy/PVA matrix occurred simultaneously upon gamma irradiation. The optimum dose for GOx immobilization in the polymer matrix found to be 40 kGy. Therefore it is clear that this irradiation technique offered a simple single process to produce Py/PVA-GOx film without additional crosslinking and polymerization agents.

  1. Indole Alkaloids from Alocasia macrorrhiza.

    PubMed

    Zhu, Ling-Hua; Chen, Cheng; Wang, Hui; Ye, Wen-Cai; Zhou, Guang-Xiong

    2012-01-01

    Five new indole alkaloids, alocasins A-E (3-7), together with known hyrtiosin B (1) and hyrtiosulawesin (2) were isolated from Alocasia macrorrhiza (L.) SCHOTT; their structures were elucidated on the basis of spectroscopic data. Compounds 1-7 were in vitro tested for cytostatic activity on human throat cancer (Hep-2), human hepatocarcinoma (Hep-G2), and human nasopharyngeal carcinoma epithelial (CNE) cell lines by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method; compounds 2, 3, 6 and 7 showed mild antiproliferative activity against Hep-2 and Hep-G2 whereas compounds 2 and 4 showed gentle antiproliferative activity against CNE.

  2. Dimeric pyrrole-imidazole alkaloids: Synthetic approaches and biosynthetic hypotheses

    PubMed Central

    Wang, Xiao; Ma, Zhiqiang; Wang, Xiaolei; De, Saptarshi; Ma, Yuyong

    2014-01-01

    The pyrrole-imidazole alkaloids are a group of structurally unique and biologically interesting marine sponge metabolites. Among them, the cyclic dimers have caught synthetic chemists’ attention particularly. Numerous synthetic strategies have been developed and various biosynthetic hypotheses have been proposed for these fascinating natural products. We discuss herein the synthetic approaches and the biosynthetic insights obtained from these studies. PMID:24828265

  3. Dimeric pyrrole-imidazole alkaloids: synthetic approaches and biosynthetic hypotheses.

    PubMed

    Wang, Xiao; Ma, Zhiqiang; Wang, Xiaolei; De, Saptarshi; Ma, Yuyong; Chen, Chuo

    2014-08-14

    The pyrrole-imidazole alkaloids are a group of structurally unique and biologically interesting marine sponge metabolites. Among them, the cyclic dimers have caught synthetic chemists' attention particularly. Numerous synthetic strategies have been developed and various biosynthetic hypotheses have been proposed for these fascinating natural products. We discuss herein the synthetic approaches and the biosynthetic insights obtained from these studies.

  4. Synthesis of polysubstituted pyrroles from sulfinimines (N-sulfinyl imines)

    PubMed Central

    Davis, Franklin A.; Bowen, Kerisha A.; Xu, He; Velvadapu, Venkata

    2008-01-01

    Polysubstituted 2-carboxylate and 2-phosphonate pyrroles are prepared by aromatization of the corresponding 3-oxo 2-carboxylate and 2-phosphonate NH-pyrrolidines using air. Reaction of electrophiles with 3-oxo pyrrolidine dianions readily introduces substituents, regioselectively at C-4 in these pyrrolidines. PMID:19421309

  5. Halogenated Indole Alkaloids from Marine Invertebrates

    PubMed Central

    Pauletti, Patrícia Mendonça; Cintra, Lucas Silva; Braguine, Caio Guedes; da Silva Filho, Ademar Alves; Silva, Márcio Luís Andrade e; Cunha, Wilson Roberto; Januário, Ana Helena

    2010-01-01

    This review discusses the isolation, structural elucidation, and biological activities of halogenated indole alkaloids obtained from marine invertebrates. Meridianins and related compounds (variolins, psammopemmins, and aplicyanins), as well as aplysinopsins and leptoclinidamines, are focused on. A compilation of the 13C-NMR spectral data of these selected natural indole alkaloids is also provided. PMID:20559487

  6. Halogenated indole alkaloids from marine invertebrates.

    PubMed

    Pauletti, Patrícia Mendonça; Cintra, Lucas Silva; Braguine, Caio Guedes; da Silva Filho, Ademar Alves; Silva, Márcio Luís Andrade E; Cunha, Wilson Roberto; Januário, Ana Helena

    2010-04-28

    This review discusses the isolation, structural elucidation, and biological activities of halogenated indole alkaloids obtained from marine invertebrates. Meridianins and related compounds (variolins, psammopemmins, and aplicyanins), as well as aplysinopsins and leptoclinidamines, are focused on. A compilation of the (13)C-NMR spectral data of these selected natural indole alkaloids is also provided.

  7. Ab initio Hartree-Fock investigation of 1- H-pyrrolo[3,2- b]pyridine-3-yl acetic acid

    NASA Astrophysics Data System (ADS)

    Ramek, Michael; Tomić, Sanja

    2001-09-01

    The potential energy surface of 1- H-pyrrolo[3,2- b]pyridine-3-yl acetic acid has been investigated via RIIF/6-31G* calculations. The stationary points and reaction paths for syn orientation of the COOH group were determined and are compared with those of the derivatives of 3-indole acetic acid, which act as plant growth hormones. 1- H-pyrrolo[3,2- b]pyridine-3-yl acetic acid forms a kinetically stable conformer with a strong intramolecular hydrogen bond, in which the COOH group is in anti orientation. The influence of this hydrogen bond on bond lengths and vibration frequencies is described.

  8. Efficient syntheses of permethylated derivatives of neolamellarin A, a pyrrolic marine natural product

    NASA Astrophysics Data System (ADS)

    Yin, Ruijuan; Jiang, Long; Wan, Shengbiao; Jiang, Tao

    2015-04-01

    The pyrrole-derived alkaloids with marine origin, especially their permethyl derivatives, have unique structures and promising biological activities. Marine natural product neolamellarins are a collection of lamellarin-like phenolic pyrrole compounds, which can inhibit hypoxia-induced HIF-1 activation. Many pyrrole-derived lamellarin-like alkaloids show potent MDR reversing activity. In this study, five permethylated derivatives of neolamellarin A were synthesized with their MDR reversing activity studied in order to identify new MDR reversal agents. A convergent strategy was adopted to synthesize the permethylated derivatives of neolamellarin A. Pyrrole was first converted into a corresponding N-trisisopropylsilyl (TIPS)-substituted derivative, then through iodination afforded 3,4-diiodinated pyrrole compound. The key intermediate, 3,4-disubstituent-1 H-pyrrole, was obtained through desilylation of 3,4-disubstituent-1-TIPS pyrrole, which was prepared from 3,4-diiodinated pyrrole derivative and aryl boronic acid ester through Suzuki cross-coupling reaction between them. Then, the intermediate, 3,4-disubstituent-1 H-pyrrole, reacted with fresh phenylacetyl chloride under n-BuLi/THF condition afforded the target compounds. Finally, we obtained five novel pyrrolic compounds, permethylated derivatives of neolamellarin A 16a-e, in 30%-37% yield through five step reactions. The bioactivity testing of these compounds are in process.

  9. Indole alkaloids from Geissospermum reticulatum.

    PubMed

    Reina, M; Ruiz-Mesia, W; López-Rodríguez, M; Ruiz-Mesia, L; González-Coloma, A; Martínez-Díaz, R

    2012-05-25

    Ten indole alkaloids were isolated from Geissospermum reticulatum, seven (1-7) from the leaves and three (8-10) from the bark. Seven were aspidospermatan-type alkaloids (1-3, 5-9), including four (5-8) with a 1-oxa-3-cyclopentene group in their molecule, which we named geissospermidine subtype. Compounds 1-3, 5-8, and 10 had not been reported previously as natural products, while 4 and 9 were the known alkaloids O-demethylaspidospermine and flavopereirine. Their structures were determined by spectroscopic techniques including 1D and 2D NMR experiments (COSY, NOESY, HSQC, HMBC). Additionally, X-ray crystallographic analyses of 1, 2, and 6 were performed. Antiparasitic activities of the ethanolic and alkaloidal extracts and of the pure alkaloids were tested against Trypanosoma cruzi and Leishmania infantum. In general, the extracts exhibited selective action and were more active against Leishmania than against Trypanosoma. Alkaloid 4 was also very active against L. infantum.

  10. Thieno[3,2-b]- and thieno[2,3-b]pyrrole bioisosteric analogues of the hallucinogen and serotonin agonist N,N-dimethyltryptamine.

    PubMed

    Blair, J B; Marona-Lewicka, D; Kanthasamy, A; Lucaites, V L; Nelson, D L; Nichols, D E

    1999-03-25

    The synthesis and biological activity of 6-[2-(N, N-dimethylamino)ethyl]-4H-thieno[3,2-b]pyrrole (3a) and 4-[2-(N, N-dimethylamino)ethyl]-6H-thieno[2,3-b]pyrrole (3b), thienopyrroles as potential bioisosteres of N,N-dimethyltryptamine (1a), are reported. Hallucinogen-like activity was evaluated in the two-lever drug discrimination paradigm using LSD- and DOI-trained rats. Neither 3a nor 3b substituted for LSD or DOI up to doses of 50 micromol/kg. By comparison, 1a fully substituted in LSD-trained rats. However, 3a and 3b fully substituted for the 5-HT1A agonist LY293284 ((-)-(4R)-6-acetyl-4-(di-n-propylamino)-1,3,4, 5-tetrahydrobenz[c,d]indole). Both 3a and 3b induced a brief "serotonin syndrome" and salivation, an indication of 5-HT1A receptor activation. At the cloned human 5-HT2A receptor 3b had about twice the affinity of 3a. At the cloned human 5-HT2B and 5-HT2C receptors, however, 3a had about twice the affinity of 3b. Therefore, thiophene lacks equivalence as a replacement for the phenyl ring in the indole nucleus of tryptamines that bind to 5-HT2 receptor subtypes and possess LSD-like behavioral effects. Whereas both of the thienopyrroles had lower affinity than the corresponding 1a at 5-HT2 receptors, 3a and 3b had significantly greater affinity than 1a at the 5-HT1A receptor. Thus, thienopyrrole does appear to serve as a potent bioisostere for the indole nucleus in compounds that bind to the serotonin 5-HT1A receptor. These differences in biological activity suggest that serotonin receptor isoforms are very sensitive to subtle changes in the electronic character of the aromatic systems of indole compounds.

  11. Crystal structures of three indole derivatives: 3-ethnyl-2-methyl-1-phenyl­sulfonyl-1H-indole, 4-phenyl­sulfonyl-3H,4H-cyclo­penta­[b]indol-1(2H)-one and 1-{2-[(E)-2-(5-chloro-2-nitro­phen­yl)ethen­yl]-1-phenyl­sulfonyl-1H-indol-3-yl}ethan-1-one chloro­form monosolvate

    PubMed Central

    Gopinath, S.; Sethusankar, K.; Ramalingam, Bose Muthu; Mohanakrishnan, Arasambattu K.

    2015-01-01

    The title compounds, C17H13NO2S, (I), C17H13NO3S, (II), and C24H17ClN2O5S·CHCl3, (III), are indole derivatives. Compounds (I) and (II) crystalize with two independent mol­ecules in the asymmetric unit. The indole ring systems in all three structures deviate only slightly from planarity, with dihedral angles between the planes of the pyrrole and benzene rings spanning the tight range 0.20 (9)–1.65 (9)°. These indole ring systems, in turn, are almost orthogonal to the phenyl­sulfonyl rings [range of dihedral angles between mean planes = 77.21 (8)–89.26 (8)°]. In the three compounds, the mol­ecular structure is stabilized by intra­molecular C—H⋯O hydrogen bonds, generating S(6) ring motifs with the sulfone O atom. In compounds (I) and (II), the two independent mol­ecules are linked by C—H⋯O hydrogen bonds and C—H⋯π inter­actions, while in compound (III), the mol­ecules are linked by C—H⋯O hydrogen bonds, generating R 2 2(22) inversion dimers. PMID:26396842

  12. [Biodegradation of pyridine under UV irradiation].

    PubMed

    Fang, Miao-Miao; Yan, Ning; Zhang, Yong-Ming

    2012-02-01

    Pyridine, a complex nitrogen-containing heterocyclic compounds, is usually difficult to degrade by means of single biological method. The internal loop photobiodegradation reactor (ILPBR) was used for degradation of pyridine in batch and continuous experiments following three protocols: photolysis alone (P), biodegradation alone (B), and intimately coupled photolysis and biodegradation (P&B) to investigate the regularity of pyridine degradation. The experimental results indicated that pyridine removal rate by P&B was fastest among three protocols in batch experiment, in which protocol B was faster than P. For initial pyridine concentration of 100 mg L(-1), the pyridine removal rates were respectively 4.95, 10.2 and 14.58 mg (L x h)(-1) corresponding to protocol P, B and P&B. Pyridine degradation kinetic equations were established based on Monod model, and the saturation constants decreased from 1920.4 mg x L(-1) for protocol B to 1094.1 mg x L(-1) for protocol P&B. Protocols P, B and P&B were also used for pyridine degradation in continuous flow and influent pyridine concentration increased from 50 to 300 mg x L(-1), and their average removal rates were respectively 15.8 mg (L x h)(-1) for protocol P, 23.1 mg x (L x h)(-1) for protocol B and 24.9 mg x (L x h)(-1) for protocol P&B, in which the removal rates were higher than that in batch. Experiments suggested that the inhibition of pyridine to biofilm could be relieved due to UV irradiation in process of intimately coupled UV photolysis and biodegradation, and biofilm had kept its bioactivity degrading pyridine and enhanced pyridine removal rates.

  13. Oxoanion Recognition by Benzene-based Tripodal Pyrrolic Receptors

    SciTech Connect

    Bill, Nathan; Kim, Dae-Sik; Kim, Sung Kuk; Park, Jung Su; Lynch, Vincent M.; Young, Neil J; Hay, Benjamin; Yang, Youjun; Anslyn, Eric; Sessler, Jonathan L.

    2012-01-01

    Two new tripodal receptors based on pyrrole- and dipyrromethane-functionalised derivatives of a sterically geared precursor, 1,3,5-tris(aminomethyl)-2,4,6-triethylbenzene, are reported; these systems, compounds 1 and 2, display high affinity and selectivity for tetrahedral anionic guests, in particular dihydrogen phosphate, pyrophosphate and hydrogen sulphate, in acetonitrile as inferred from isothermal titration calorimetry measurements. Support for the anion-binding ability of these systems comes from theoretical calculations and a single-crystal X-ray diffraction structure of the 2:2 (host:guest) dihydrogen phosphate complex is obtained in the case of the pyrrole-based receptor system, 1. Keywords anion receptors, dihydrogen phosphate, hydrogen sulphate, X-ray structure, theoretical calculations.

  14. Electrochemical synthesis and surface characterization of (pyrrole+2-methylfuran) copolymer

    NASA Astrophysics Data System (ADS)

    Djaouane, Linda; Nessark, Belkacem; Sibous, Lakhdar

    2017-02-01

    Electrochemical copolymerization of pyrrole (Py) and 2-methylfuran (2 MF) was performed on platinum and ITO substrates in acetonitrile/lithium perchlorate solution, using cyclic voltammetry method. The electrochemical behavior of the modified electrode surface by polypyrrole, poly(2-methylfuran) homopolymers and (pyrrole+2-methylfuran) copolymer was characterized by cyclic voltammetry, electrochemical impedance spectroscopy (EIS), UV-visible spectroscopy, atomic force microscopy (AFM) and scanning electron microscopy (SEM). The cyclic voltammetry shows anodic and cathodic peaks which are characteristic of the oxidation and the reduction of the formed films. The electrochemical impedance spectroscopy confirmed the results obtained by cyclic voltammetry. AFM and SEM analyses proved as well that the morphology and the electrochemical properties of the polypyrrole film are modified in the presence of 2-methylfuran.

  15. Gas Chromatographic Analysis of Acidic Indole Auxins in Nicotiana1

    PubMed Central

    Bayer, Margret H.

    1969-01-01

    Acidic indole auxins have been extracted from N. glauca, N. langsdorffii and their 2 tumor-prone 4n- and 2n-hybrids. After purification of the extracts and thin-layer chromatography, acidic indoles were subjected to esterification and gas chromatography. The esters of 4 indole acids were detected and determined: indole-3-acetic acid, indole-3-carboxylic acid, indole-3-propionic acid and indole-3-butyric acid. The indolic nature of fractionated samples was confirmed by spectrophotofluorometry and the physiological significance of the indole esters proven in a biotest. A substantial increase in extractable indole-3-butyric acid in the tumor-prone hybrids suggests an additional pathway of auxin synthesis in these tissues. PMID:5774173

  16. Detoxification of Indole by an Indole-Induced Flavoprotein Oxygenase from Acinetobacter baumannii

    PubMed Central

    Lin, Guang-Huey; Chen, Hao-Ping; Shu, Hung-Yu

    2015-01-01

    Indole, a derivative of the amino acid tryptophan, is a toxic signaling molecule, which can inhibit bacterial growth. To overcome indole-induced toxicity, many bacteria have developed enzymatic defense systems to convert indole to non-toxic, water-insoluble indigo. We previously demonstrated that, like other aromatic compound-degrading bacteria, Acinetobacter baumannii can also convert indole to indigo. However, no work has been published investigating this mechanism. Here, we have shown that the growth of wild-type A. baumannii is severely inhibited in the presence of 3.5 mM indole. However, at lower concentrations, growth is stable, implying that the bacteria may be utilizing a survival mechanism to oxidize indole. To this end, we have identified a flavoprotein oxygenase encoded by the iifC gene of A. baumannii. Further, our results suggest that expressing this recombinant oxygenase protein in Escherichia coli can drive indole oxidation to indigo in vitro. Genome analysis shows that the iif operon is exclusively present in the genomes of A. baumannii and Pseudomonas syringae pv. actinidiae. Quantitative PCR and Western blot analysis also indicate that the iif operon is activated by indole through the AraC-like transcriptional regulator IifR. Taken together, these data suggest that this species of bacteria utilizes a novel indole-detoxification mechanism that is modulated by IifC, a protein that appears to be, at least to some extent, regulated by IifR. PMID:26390211

  17. Antiproliferative and proapoptotic effects of a pyrrole containing arylthioindole in human Jurkat leukemia cell line and multidrug-resistant Jurkat/A4 cells

    PubMed Central

    Philchenkov, Alex A; Zavelevich, Michael P; Tryndyak, Volodymyr P; Kuiava, Ludmila M; Blokhin, Dmitry Yu; Miura, Koh; Silvestri, Romano; Pogribny, Igor P

    2015-01-01

    Recently, a series of novel arylthioindole compounds, potent inhibitors of tubulin polymerization and cancer cell growth, were synthesized. In the present study the effects of 2-(1H-pyrrol-3-yl)-3-((3,4,5-trimethoxyphenyl)thio)-1H-indole (ATI5 compound) on cell proliferation, cell cycle progression, and induction of apoptosis in human T-cell acute leukemia Jurkat cells and their multidrug resistant Jurkat/A4 subline were investigated. Treatment of the Jurkat cells with the ATI5 compound for 48 hrs resulted in a strong G2/M cell cycle arrest and p53-independent apoptotic cell death accompanied by the induction of the active form of caspase-3 and poly(ADP-ribose) polymerase-1 (PARP-1) cleavage. ATI5 treatment also caused non-cell death related mitotic arrest in multidrug resistant Jurkat/A4 cells after 48 hrs of treatment suggesting promising opportunities for the further design of pyrrole-containing ATI compounds as anticancer agents. Cell death resistance of Jurkat/A4 cells to ATI5 compound was associated with alterations in the expression of pro-survival and anti-apoptotic protein-coding and microRNA genes. More importantly, findings showing that ATI5 treatment induced p53-independent apoptosis are of great importance from a therapeutic point of view since p53 mutations are common genetic alterations in human neoplasms. PMID:26785947

  18. Evaluation of Two Spot-Indole Reagents

    PubMed Central

    Lowrance, B. L.; Reich, P.; Traub, W. H.

    1969-01-01

    Two spot-indole reagents, p-dimethylaminobenzaldehyde (DMABA) and p-dimethylaminocinnamaldehyde, were evaluated quantitatively. Although fourfold less sensitive, DMABA proved to be more stable and economical. PMID:4894726

  19. Indole-3-thio­uronium nitrate

    PubMed Central

    Lutz, Martin; Spek, Anthony L.; van der Geer, Erwin P. L.; van Koten, Gerard; Klein Gebbink, Robertus J. M.

    2008-01-01

    In the title compound, C9H10N3S+·NO3 −, the indole ring system and the thiouronium group are nearly perpendicular, with a dihedral angle of 88.62 (6)°. Hydrogen bonding generates two-dimensional networks which are linked to each other via π stacking inter­actions of the indole groups [average inter-planar ring–ring distance of 3.449 (2) Å]. PMID:21200759

  20. Indoles in edible members of the Cruciferae.

    PubMed

    Wall, M E; Taylor, H; Perera, P; Wani, M C

    1988-01-01

    Antimutagenic fractions from collards yielded indole-3-carboxaldehyde [4] and traces of indole-3-acetonitrile [2]. The compounds had no antimutagenic activity. An analytical procedure for various indoles in plants was developed based on reversed-phase hplc. The indoles studied included the 3-carbinol 1, the acetonitrile 2, the carboxaldehyde 4, the 3-carboxylic acid 5, and the 3-acetic acid 6. Many Cruciferae and non-Cruciferae were analyzed. The latter did not contain measurable quantities of these compounds. In the case of the Cruciferae--with the exception of collards, which consistently indicated the presence of the aldehyde 4--major indole found was the nitrile 2. Although a particularly careful search for the carbinol 1 was conducted, only trace levels were noted. A review of the literature indicates that the content and occurrence of this indole in plants have been heavily overestimated. Because of the low levels found in the Cruciferae, our studies indicate that the role of the compound as a dietary factor may be questionable.

  1. Pyridine-4-carbaldehyde 4-phenylsemicarbazone

    PubMed Central

    Mendoza-Meroño, Rafael; Menéndez-Taboada, Laura; Fernández-Zapico, Eva; García-Granda, Santiago

    2011-01-01

    In the title compound, C13H12N4O, the semicarbazone fragment links a benzene and a pyridine ring in the structure. The crystal packing is stabilized by strong inter­molecular N—H⋯O hydrogen bonds, which connect two mol­ecules to form a synthon unit, and by N—H⋯N hydrogen bonds and weak C—H⋯π inter­actions. The mol­ecular conformation is stabil­ized by intra­molecular N—H⋯N and C—H⋯O inter­actions. PMID:21754444

  2. Pyridine-2,3-diamine

    PubMed Central

    Betz, Richard; Gerber, Thomas; Hosten, Eric; Schalekamp, Henk

    2011-01-01

    The mol­ecule of the title pyridine derivative, C5H7N3, shows approximately non-crystallographic C s symmetry. Intra­cyclic angles cover the range 117.50 (14)–123.03 (15)°. In the crystal, N—H⋯N hydrogen bonds connect mol­ecules into a three-dimensional network. The closest inter­centroid distance between two π-systems occurs with the c-axis repeat at 3.9064 (12) Å. PMID:22091168

  3. Pyridine N-oxide and pyridine-d5 N-oxide: an electrospray/tandem mass spectrometric study carried out at high mass resolution.

    PubMed

    March, Raymond E; Stadey, Christopher J; Lewars, Errol G

    2005-01-01

    A mass spectrometric study of pyridine N-oxide and pyridine-d5 N-oxide was carried out with a hybrid quadrupole/time-of-flight (TOF) mass spectrometer coupled with an electrospray (ES) source. In addition to the observation of protonated, sodiated, and proton-bound dimers of pyridine N-oxide and pyridine-d5 N-oxide, mass scans revealed the presence of several doubly-charged ion species. Doubly-charged ions of m/z 191 were identified as diprotonated tetramers of pyridine N-oxide; a structure has been proposed for the diprotonated tetramer and its energy relative to that of protonated pyridine N-oxide has been obtained from geometry optimizations. The principal ion species observed were subjected to collision-induced dissociation; accurate mass measurements were made of each fragment ion so as to determine its elemental composition. On the basis of mass spectrometric evidence, it is suggested that dissociation of pyridine N-oxide may occur during the ES process and the resulting fragments become embedded in doubly-charged ions. The proton affinity for both pyridine N-oxide and pyridine-d5 N-oxide was calculated; the difference between these proton affinities was compared with an experimentally determined difference between the proton affinities of pyridine N-oxide and pyridine-d5 N-oxide.

  4. ESP and ESM1 mediate indol-3-acetonitrile production from indol-3-ylmethyl glucosinolate in Arabidopsis.

    PubMed

    Burow, Meike; Zhang, Zhi-Yong; Ober, James A; Lambrix, Virginia M; Wittstock, Ute; Gershenzon, Jonathan; Kliebenstein, Daniel J

    2008-02-01

    Glucosinolates are plant secondary metabolites that act as direct defenses against insect herbivores and various pathogens. Recent analysis has shown that methionine-derived glucosinolates are hydrolyzed/activated into either nitriles or isothiocyanates depending upon the plants genotype at multiple loci. While it has been hypothesized that tryptophan-derived glucosinolates can be a source of indole-acetonitriles, it has not been explicitly shown if the same proteins control nitrile production from tryptophan-derived glucosinolates as from methionine-derived glucosinolates. In this report, we formally test if the proteins involved in controlling aliphatic glucosinolate hydrolysis during tissue disruption can control production of nitriles during indolic glucosinolate hydrolysis. We show that myrosinase is not sufficient for indol-3-acetonitrile production from indol-3-ylmethyl glucosinolate and requires the presence of functional epithospecifier protein in planta and in vitro to produce significant levels of indol-3-acetonitrile. This reaction is also controlled by the Epithiospecifier modifier 1 gene. Thus, like formation of nitriles from aliphatic glucosinolates, indol-3-acetonitrile production following tissue disruption is controlled by multiple loci raising the potential for complex regulation and fine tuning of indol-3-acetonitrile production from indol-3-ylmethyl glucosinolate.

  5. 3-(2,5-Dihydro-1H-pyrrol-2-ylmethoxy)pyridines: synthesis and analgesic activity.

    PubMed

    Baraznenok, Ivan L; Jonsson, Emma; Claesson, Alf

    2005-03-15

    We disclose an efficient procedure for the preparation of ethers of 2-substituted 2-hydroxymethylpyrroline and of 2-aminomethyl-3-pyrrolines, involving, as a key step, formation and nucleophilic ring opening of a cyclic sulfamidate. Several new analogs of epibatidine (1) and tebanicline (ABT-594, 2) were prepared and tested for analgesic activity in the mouse formalin model.

  6. Enzymic synthesis of 1-O-indol-3-ylacetyl-beta-D-glucose and indol-3-ylacetyl-myo-inositol.

    PubMed Central

    Michalczuk, L; Bandurski, R S

    1982-01-01

    An enzyme fraction from extracts of immature kernels of Zea mays catalyses the formation of 1-O-indol-3-ylacetyl-beta-D-glucose from indol-3-ylacetic acid and UDP-glucose. A second enzyme fraction catalyses the formation of indol-3-ylacetyl-myo-inositol from 1-O-indol-3-ylacetyl-beta-D-glucose and myo-inositol. To our knowledge, this is the first example of hydroxy-group acylation by a 1-O-acyl sugar. The following reaction sequence is proposed: Indol-3-ylacetic acid + UDP-glucose leads to indol-3-ylacetylglucose + UDP (1) Indol-3-ylacetylglucose + myo-inositol leads to indol-3-ylacetyl-myo-inositol + glucose (2) The enzyme catalysing reaction (1) is called UDP-glucose:indol-3-ylacetate glucosyl-transferase (indol-3-ylacetylglucose synthase), and that catalysing reaction (2) is indol-3-ylacetylglucose:myo-inositol indol-3-ylacetyltransferase (indol-3-ylacetyl-myo-inositol synthase). We further show that indol-3-ylacetylglucose synthase is specific for UDP-glucose and, at the stage of purity tested, the enzyme will use either indol-3-ylacetic acid or naphthalene-1-acetic acid, but not 2.4-dichlorophenoxyacetic acid, as glucose acceptor. The indol-3-ylacetyl-myo-inositol synthase is specific for indol-3-ylacetyl-glucose and will not use naphthalene-1-acetylglucose as substrate, and it is specific for myo-inositol among the alcohol acceptors tested. Thus, of the auxins tested, only indol-3-ylacetic acid forms the myo-inositol ester. PMID:6218801

  7. Pyrrolic molecular rotors acting as viscosity sensors with high fluorescence contrast.

    PubMed

    Lee, Seung-Chul; Heo, Jeongyun; Ryu, Jong-Wan; Lee, Chang-Lyoul; Kim, Sehoon; Tae, Joon-Sung; Rhee, Byung-Ohk; Kim, Sang-Wook; Kwon, O-Pil

    2016-11-17

    New pyrrolic viscosity sensors exhibit one order of magnitude higher fluorescence contrast compared to that of the conventional phenolic analogues due to the viscosity-sensitive rotation of the asymmetric pyrrole group and successfully demonstrate mapping of intracellular viscosity by fluorescence lifetime imaging microscopy.

  8. Merging gold and organocatalysis: a facile asymmetric synthesis of annulated pyrroles.

    PubMed

    Hack, Daniel; Loh, Charles C J; Hartmann, Jan M; Raabe, Gerhard; Enders, Dieter

    2014-04-01

    The combination of cinchona-alkaloid-derived primary amine and Au(I) -phosphine catalysts allowed the selective C-H functionalization of two adjacent carbon atoms of pyrroles under mild reaction conditions. This sequential dual activation provides seven-membered-ring-annulated pyrrole derivatives in excellent yields and enantioselectivities.

  9. Synthetic approaches to tetracyclic pyrrole imidazole marine alkaloids.

    PubMed

    Imaoka, Takuya; Iwata, Makoto; Akimoto, Takafumi; Nagasawa, Kazuo

    2013-07-01

    Oroidin derived, pyrrole imidazole marine alkaloids (PIAs) are attractive targets for synthetic organic chemists because of their structural complexity and diversity, as well as their interesting biological activities. A number of efforts have been carried out to develop strategies for the synthesis of these natural products. Members of PIAs (eg., 2-7), which contain tetracyclic ring systems possessing characteristic cyclic guanidine or urea moieties, show significant biological activities including anticancer activity and agonistic activity against the adrenoceptor. In this review, investigations of the total synthesis of the representative tetracyclic PIAs, dibromophakellin (2) and dibromophakellstatin (3), are described.

  10. Electrochemically Initiated Chain Polymerization of Pyrrole in Aqueous Media

    DTIC Science & Technology

    1991-10-21

    ACCESSION NO. -1 .... :on., Virginia 22203:-1714 TITLE (inciuoe Security Classification) Liec-rochemica!ly initiated Chain Polynerization of Pyrrole in...ABSTRACT SECURITY C-ASSIFICATION " U4CLASS!FIED/UNUM’TTD E SAME AS P07, DTIC USERS S o$.C ff e 2a NAME O RESPONSIBLE INDIViDUAL 22 . TELEP H.ONE...electroacfive, resembling regular polypyrrole. Wudl et a123 have reported that electropolymerization of isothianaphthene in LiBF4 leads to the formatioi, of an

  11. Riboflavin production during growth of Micrococcus luteus on pyridine

    SciTech Connect

    Sims, G.K. ); O'Loughlin, E.J. )

    1992-10-01

    Micrococcus luteus produced 29 {mu}M riboflavin during growth on 6.5 mM pyridine but not during growth on other substrates. On the basic of the results of radiolabelling studies, riboflavin was not directly synthesized from pyridine. Pyridine may interfere with riboflavin biosynthesis or elicit a general stress response in M. luteus. The optimum concentration of pyridine for both growth of the organism and pyridine degradation was 13 mM. Above 25 mM, pyridine temporarily inhibited growth, pyridine degradation, oxygen uptake, and pigment production.

  12. Four pyrrole derivatives used as building blocks in the synthesis of minor-groove binders

    PubMed Central

    Kennedy, Alan R.; Khalaf, Abedawn I.; Suckling, Colin J.

    2017-01-01

    The title nitro­pyrrole-based compounds, C7H8N2O4, (I) (ethyl 4-nitro-1H-pyrrole-2-carboxyl­ate), its derivative C12H14N2O4, (II) [ethyl 4-nitro-1-(4-pent­yn­yl)-1H-pyrrole-2-carboxyl­ate], C15H26N4O3, (III) {N-[3-(di­methyamino)prop­yl]-1-isopentyl-4-nitro-1H-pyrrole-2-carboxamide}, and C20H27N9O5, (IV) {1-(3-azido­prop­yl)-4-(1-methyl-4-nitro-1H-pyrrole-2-carboxamido)-N-[2-(morpholin-4-yl)eth­yl]-1H-pyrrole-2-carboxamide}, are inter­mediates used in the synthesis of modified DNA minor-groove binders. In all four compounds, the nitro groups lie in the plane of the pyrrole ring. In compounds (I) and (II), the ester groups also lie in the plane of the pyrrole ring. In compound (III), both of the other substituents lie out of the plane of the pyrrole ring. In the case of compound (IV), the coplanarity extends to the second pyrrole ring and through both amide groups. In the crystals of all four compounds, layer-like structures are formed, via a combination of N—H⋯O and C—H⋯O hydrogen bonds for (I), (III) and (IV), but by only C—H⋯O hydrogen bonds for (II). PMID:28217354

  13. The Contrasting Alkylations of 4-(Dimethylaminomethyl)pyridine and 4-(Dimethylamino)pyridine: An Organic Chemistry Experiment

    ERIC Educational Resources Information Center

    Jantzi, Kevin L.; Wiltrakis, Susan; Wolf, Lauren; Weber, Anna; Cardinal, Josh; Krieter, Katie

    2011-01-01

    A critical factor for the increased nucleophilicity of the pyridine nitrogen in 4-(dimethylamino)pyridine (DMAP) is electron donation via resonance from the amino group into the aromatic ring that increases electron density on the pyridine nitrogen. To explore how important this resonance effect is, 4-(dimethylaminomethyl)pyridine (DMAMP) was…

  14. The Contrasting Alkylations of 4-(Dimethylaminomethyl)pyridine and 4-(Dimethylamino)pyridine: An Organic Chemistry Experiment

    ERIC Educational Resources Information Center

    Jantzi, Kevin L.; Wiltrakis, Susan; Wolf, Lauren; Weber, Anna; Cardinal, Josh; Krieter, Katie

    2011-01-01

    A critical factor for the increased nucleophilicity of the pyridine nitrogen in 4-(dimethylamino)pyridine (DMAP) is electron donation via resonance from the amino group into the aromatic ring that increases electron density on the pyridine nitrogen. To explore how important this resonance effect is, 4-(dimethylaminomethyl)pyridine (DMAMP) was…

  15. Anti-Inflammatory Effects of Protein Kinase Inhibitor Pyrrol Derivate

    PubMed Central

    Yena, Maryna S.; Kotlyar, Iryna P.; Ogloblya, Olexandr V.; Rybalchenko, Volodymyr K.

    2016-01-01

    In our previous studies we showed antitumor and anti-inflammatory activities of protein kinases inhibitor pyrrol derivate 1-(4-Cl-benzyl)-3-Cl-4-(CF3-fenylamino)-1H-pyrrol-2,5-dione (MI-1) on rat colon cancer model. Therefore anti-inflammatory effect of MI-1 on rat acetic acid induced ulcerative colitis (UC) model was aimed to be discovered. The anti-inflammatory effects of MI-1 (2.7 mg/kg daily) compared to reference drug Prednisolone (0.7 mg/kg daily) after 14-day usage were evaluated on macro- and light microscopy levels and expressed in 21-grade scale. Redox status of bowel mucosa was also estimated. It was shown that in UC group the grade of total injury (GTI) was equal to 9.6 (GTIcontrol = 0). Increase of malonic dialdehyde (MDA) by 89% and protein carbonyl groups (PCG) by 60% and decrease of superoxide dismutase (SOD) by 40% were also observed. Prednisolone decreased GTI to 3 and leveled SOD activity, but MDA and PCG remained higher than control ones by 52% and 42%, respectively. MI-1 restored colon mucosa integrity and decreased mucosa inflammation down to GTI = 0.5 and leveled PCG and SOD. Thus, MI-1 possessed anti-inflammatory properties, which were more expressed that Prednisolone ones, as well as normalized mucosa redox balance, and so has a prospect for correction of inflammatory processes. PMID:28101521

  16. Anti-Inflammatory Effects of Protein Kinase Inhibitor Pyrrol Derivate.

    PubMed

    Kuznietsova, Halyna M; Yena, Maryna S; Kotlyar, Iryna P; Ogloblya, Olexandr V; Rybalchenko, Volodymyr K

    2016-01-01

    In our previous studies we showed antitumor and anti-inflammatory activities of protein kinases inhibitor pyrrol derivate 1-(4-Cl-benzyl)-3-Cl-4-(CF3-fenylamino)-1H-pyrrol-2,5-dione (MI-1) on rat colon cancer model. Therefore anti-inflammatory effect of MI-1 on rat acetic acid induced ulcerative colitis (UC) model was aimed to be discovered. The anti-inflammatory effects of MI-1 (2.7 mg/kg daily) compared to reference drug Prednisolone (0.7 mg/kg daily) after 14-day usage were evaluated on macro- and light microscopy levels and expressed in 21-grade scale. Redox status of bowel mucosa was also estimated. It was shown that in UC group the grade of total injury (GTI) was equal to 9.6 (GTIcontrol = 0). Increase of malonic dialdehyde (MDA) by 89% and protein carbonyl groups (PCG) by 60% and decrease of superoxide dismutase (SOD) by 40% were also observed. Prednisolone decreased GTI to 3 and leveled SOD activity, but MDA and PCG remained higher than control ones by 52% and 42%, respectively. MI-1 restored colon mucosa integrity and decreased mucosa inflammation down to GTI = 0.5 and leveled PCG and SOD. Thus, MI-1 possessed anti-inflammatory properties, which were more expressed that Prednisolone ones, as well as normalized mucosa redox balance, and so has a prospect for correction of inflammatory processes.

  17. Novel 1H-pyrrolo[2,3-b]pyridine derivative nortopsentin analogues: synthesis and antitumor activity in peritoneal mesothelioma experimental models.

    PubMed

    Carbone, Anna; Pennati, Marzia; Parrino, Barbara; Lopergolo, Alessia; Barraja, Paola; Montalbano, Alessandra; Spanò, Virginia; Sbarra, Stefania; Doldi, Valentina; De Cesare, Michelandrea; Cirrincione, Girolamo; Diana, Patrizia; Zaffaroni, Nadia

    2013-09-12

    In this study, we describe the synthesis of new nortopsentin analogues, 1H-pyrrolo[2,3-b]pyridine derivatives and their biological effects in experimental models of diffuse malignant peritoneal mesothelioma (DMPM), a rare and rapidly fatal disease, poorly responsive to conventional therapies. The three most active compounds, 1f (3-[2-(5-fluoro-1-methyl-1H-indol-3-yl)-1,3-thiazol-4-yl]-1H-pyrrolo[2,3-b]pyridine), 3f (3-[2-(1H-indol-3-yl)-1,3-thiazol-4-yl]-1-methyl-1H-pyrrolo[2,3-b]pyridine), and 1l (3-[2-(5-fluoro-1-methyl-1H-indol-3-yl)-1,3-thiazol-4-yl]-1-methyl-1H-pyrrolo[2,3-b] pyridine), which were shown to act as cyclin-dependent kinase 1 inhibitors, consistently reduced DMPM cell proliferation and induced a caspase-dependent apoptotic response, with a concomitant reduction of the expression of the active Thr(34)-phosphorylated form of the antiapoptotic protein survivin. Moreover, the combined treatment of DMPM cells with 3f derivative and paclitaxel produced a synergistic cytotoxic effect, which was paralleled by an enhanced apoptotic response. In the mouse model, i.p. administration of 1f, 3f, and 1l derivatives was effective, resulting in a significant tumor volume inhibition of DMPM xenografts (range, 58-75%) at well-tolerated doses, and two complete responses were observed in each treatment group.

  18. Indoles: Industrial, Agricultural and Over-the-Counter Uses

    NASA Astrophysics Data System (ADS)

    Barden, Timothy C.

    Indole-containing compounds are best known for their medicinal properties in the pharmaceutical industry. Although to a lesser degree, the indole motif none-the-less appears in many significant products across the entire chemical industry. This chapter describes the role that indole plays in a more commodity setting and provides examples illustrating these uses.

  19. New indole alkaloid from Peschiera affinis (Apocynaceae).

    PubMed

    Santos, Allana Kellen L; Machado, Luciana L; Bizerra, Ayla Marcia C; Monte, Francisco José Q; Santiago, Gilvandete M P; Braz-Filho, Raimundo; Lemos, Telma L G

    2012-06-01

    A new indole alkaloid of the pyridocarbazole type, named 6N-hydroxy-olivacine, and two known compounds, 2N-oxide-olivacine and olivacine, were isolated from roots of Peschiera affinis. The structures of the compounds were determined by spectroscopic {IR and extensive NMR (COSY, HMQC, HMBCand NOESY)} and EIMS analysis.

  20. A new indole alkaloid from Alstonia scholaris.

    PubMed

    Jain, Luna; Pandey, M B; Singh, Sarita; Singh, A K; Pandey, V B

    2009-01-01

    A new indole alkaloid, N-formylscholarine, together with picrinine, strictamine and nareline has been isolated from the fruit pods of Alstonia scholaris, and their structures were established by various spectral data. This is the first report of these alkaloids in A. scholaris fruit pods.

  1. Site- and Regioselective Monoalkenylation of Pyrroles with Alkynes via Cp*Co(III) Catalysis.

    PubMed

    Tanaka, Ryo; Ikemoto, Hideya; Kanai, Motomu; Yoshino, Tatsuhiko; Matsunaga, Shigeki

    2016-11-04

    A site-, regio-, syn-, and monoselective alkenylation of dimethylcarbamoyl-protected pyrroles proceeded using a catalytic amount of [Cp*Co(CH3CN)3](SbF6)2 and KOAc. A variety of internal alkynes with several functional groups and a terminal alkyne afforded hydropyrrolation products in a selective manner in good to excellent yield. The site-selectivity (C2/C5 selectivity) observed for C3-substituted pyrroles is noteworthy because Cp*Rh(III)-catalyzed conditions afforded only a moderate yield and low selectivity. The conditions described here provide general and straightforward access to unsymmetrically mono- and disubstituted pyrrole derivatives.

  2. A Submarine Journey: The Pyrrole-Imidazole Alkaloids †

    PubMed Central

    Forte, Barbara; Malgesini, Beatrice; Piutti, Claudia; Quartieri, Francesca; Scolaro, Alessandra; Papeo, Gianluca

    2009-01-01

    In his most celebrated tale “The Picture of Dorian Gray”, Oscar Wilde stated that “those who go beneath the surface do so at their peril”. This sentence could be a prophetical warning for the practitioner who voluntarily challenges himself with trying to synthesize marine sponge-deriving pyrrole-imidazole alkaloids. This now nearly triple-digit membered community has been growing exponentially in the last 20 years, both in terms of new representatives and topological complexity – from simple, achiral oroidin to the breathtaking 12-ring stylissadines A and B, each possessing 16 stereocenters. While the biosynthesis and the role in the sponge economy of most of these alkaloids still lies in the realm of speculations, significant biological activities for some of them have clearly emerged. This review will account for the progress in achieving the total synthesis of the more biologically enticing members of this class of natural products. PMID:20098608

  3. Experimental and theoretical study of 4-formyl pyrrole derived aroylhydrazones

    NASA Astrophysics Data System (ADS)

    Rawat, Poonam; Singh, R. N.

    2015-03-01

    Two new 4-formyl pyrrole derived aroylhydrazones (3a, b) from ethyl 4-formyl-3,5-dimetyl-1H-pyrrole-2-carboxylate and aroylhydrazides (3,5-dinitrobenzohydrazide/2-hydrazinocarbonyl-N-phenyl-acetamide) have been synthesized and characterized by various spectroscopic techniques 1H NMR, Mass, UV-Visible and FT-IR. The calculated thermodynamic parameters show that the formation of 3a as spontaneous, whereas 3b as non-spontaneous. TD-DFT has been used to calculate the absorption wavelengths, oscillator strength (f) and the nature of electronic excitations. Natural bond orbital (NBO) analysis has been carried out to explore the various conjugative and hyperconjugative interactions and their second order stabilization energy (E(2)) within monomer and its dimer. The dimer formation of 3a, 3b due to result of intermolecular hydrogen bonding N1sbnd H30⋯O84, N1sbnd H28⋯O60 is obvious in 1H NMR, NBO and FT-IR as down field chemical shifts, n(O84) → σ∗(N1sbnd H30), n(O60) → σ∗(N1sbnd H28) interactions, vibrational red shifts, respectively. To determine the strength and nature of hydrogen bonding, topological parameters at bond critical points (BCP) have been analyzed by 'Quantum theory of Atoms in molecules' (QTAIM) in detail. The global electrophilicity index (ω) has been calculated to determine the relative electrophilic strength of molecules. The local reactivity descriptors analyses such as Fukui functions (fk+, fk-), local softnesses (sk+, sk-) and electrophilicity indices (ωk+, ωk-) have been performed to determine the reactive sites within molecules. The first hyperpolarizabilities (β0) of 3a, b have been computed to evaluate the non-linear optical (NLO) response of the investigated molecules.

  4. Indole-containing new types of dyes and their UV-vis and NMR spectra and electronic structures: Experimental and theoretical study

    NASA Astrophysics Data System (ADS)

    Kuzu, Burak; Menges, Nurettin

    2016-06-01

    Indole containing dyes were synthesized via a simple method with high yield. These molecules have different colors and UV-vis spectra of them were recorded. Impact of solvents on absorbances was investigated and it was observed that basic solvent such as DMF and pyridine have blue shift. TD-DFT calculations were done and results were compared with experimental data. NMR data of molecules were analyzed and tautomeric forms of colorants and their ratio were determined. It was find out that two tautomers might be formed in solution, called indole and indolenine form. HOMO-LUMO and energy gaps were calculated and plotted. Furthermore, molecular electrostatic potentials were simulated to find out electrophilic and nucleophilic regions.

  5. Auto-oligomerization and hydration of pyrrole revealed by x-ray absorption spectroscopy

    SciTech Connect

    Advanced Light Source; Schwartz, Craig P.; Uejio, Janel S.; Duffin, Andrew M.; England, Alice H.; Prendergast, David; Saykally, Richard J

    2009-05-29

    Near edge x-ray absorption fine structure (NEXAFS) spectra have been measured at the carbon and nitrogen K-edges of the prototypical aromatic molecule, pyrrole, both in the gas phase and when solvated in water, and compared with spectra simulated using a combination of classical molecular dynamics and first principles density functional theory in the excited state core hole approximation. The excellent agreement enabled detailed assignments. Pyrrole is highly reactive, particularly in water, and reaction products formed by the auto-oligomerization of pyrrole are identified. The solvated spectra have been measured at two different temperatures, indicating that the final states remain largely unaffected by both hydration and temperature. This is somewhat unexpected, since the nitrogen in pyrrole can donate a hydrogen bond to water.

  6. Pyrrole as a promising electrolyte additive to trap polysulfides for lithium-sulfur batteries

    NASA Astrophysics Data System (ADS)

    Yang, Wu; Yang, Wang; Song, Ailing; Gao, Lijun; Sun, Gang; Shao, Guangjie

    2017-04-01

    Lithium-sulfur batteries are a promising energy storage devices beyond conventional lithium ion batteries. However, the ;shuttle effect; of soluble polysulfides is a major barrier between electrodes, resulting in rapid capacity fading. To address above issue, pyrrole has been investigated as an electrolyte additive to trap polysulfides. When pyrrole is added into electrolyte, a surface protective layer of polypyrrole can be formed on the sulfur cathode, which not only acts as a conductive agent to provide an effective electron conduction path but also acts as an absorbing agent and barrier layer suppressing the diffusion of polysulfide intermediates. The results demonstrate that an appropriate amount of pyrrole added into the electrolyte leads to excellent cycling stability and rate capability. Apparently, pyrrole is an effective additive for the entrapment of polysulfides of lithium-sulfur batteries.

  7. One-Pot Conversion of Carbohydrates into Pyrrole-2-carbaldehydes as Sustainable Platform Chemicals.

    PubMed

    Adhikary, Nirmal Das; Kwon, Sunjeong; Chung, Wook-Jin; Koo, Sangho

    2015-08-07

    A practical conversion method of carbohydrates into N-substituted 5-(hydroxymethyl)pyrrole-2-carbaldehydes (pyrralines) was developed by the reaction with primary amines and oxalic acid in DMSO at 90 °C. Further cyclization of the highly functionalized pyrralines afforded the pyrrole-fused poly-heterocyclic compounds as potential intermediates for drugs, food flavors, and functional materials. The mild Maillard variant of carbohydrates and amino esters in heated DMSO with oxalic acid expeditiously produced the pyrrole-2-carbaldehyde skeleton, which can be concisely transformed into the pyrrole alkaloid natural products, 2-benzyl- and 2-methylpyrrolo[1,4]oxazin-3-ones 8 and 9, lobechine 10, and (-)-hanishin 11 in 23-32% overall yields from each carbohydrate.

  8. Bipyrrole-Strapped Calix[4]pyrroles: Strong Anion Receptors That Extract the Sulfate Anion

    SciTech Connect

    Kim, Sung Kuk; Lee, Juhoon; Williams, Neil J; Lynch, Vincent M.; Hay, Benjamin; Moyer, Bruce A; Sessler, Jonathan L.

    2014-01-01

    Cage-type calix[4]pyrroles 2 and 3 bearing two additional pyrrole groups on the strap have been synthesized. Compared with the parent calix[4]pyrrole (1), they were found to exhibit remarkably enhanced affinities for anions, including the sulfate anion (TBA+ salts), in organic media (CD2Cl2). This increase is ascribed to participation of the bipyrrole units in anion binding. Receptors 2 and 3 extract the hydrophilic sulfate anion (as the methyltrialkyl(C8-10)ammonium (A336+) salt)) from aqueous media into a chloroform phase with significantly improved efficiency (>10-fold relative to calix[4]pyrrole 1). These two receptors also solubilize into chloroform the otherwise insoluble sulfate salt, (TMA)2SO4 (tetramethylammonium sulfate).

  9. An electrogenerated poly(pyrrole-benzophenone) film for the photografting of proteins.

    PubMed

    Cosnier, Serge; Senillou, Anne

    2003-02-07

    A photoreactive organic polymer was prepared by oxidative electrochemical polymerization of a pyrrole-benzophenone derivative on conductive surfaces; the resulting polypyrrolic film allowed, upon irradiation, the reagentless covalent grafting of proteins.

  10. Porphinogen Formation from the Co-Oligomerization of Formaldehyde and Pyrrole: Free Energy Pathways.

    PubMed

    Kua, Jeremy; Loli, Helen

    2017-09-29

    We have investigated the non-oxidative stepwise co-oligomerization of formaldehyde and pyrrole to form porphinogen using density functional theory calculations that include free energy corrections. While the addition of formaldehyde to the pyrrole nitrogen is kinetically favored, thermodynamics suggest that this reaction is reversible in aqueous solution. The more thermodynamically favorable addition of formaldehyde to the ortho-carbon of pyrrole begins a step-wise process forming dipyrromethane via an azafulvene intermediate. Subsequent additions of formaldehyde and pyrrole lead to bilanes (linear tetrapyrroles) which favorably cyclize to form porphinogen. Porphinogen is a precursor to porphin, the simplest unsubstituted porphyrin that could have played a role in primitive metabolism at the origin of life.

  11. The Curious Case of Pyridine - Water

    NASA Astrophysics Data System (ADS)

    Mackenzie, Becca; Dewberry, Chris; Smith, CJ; Cornelius, Ryan D.; Leopold, Ken

    2016-06-01

    The rotational spectrum of the pyridine\\cdotswater complex has been observed in the 2-18 GHz region using chirped-pulse and cavity Fourier transform microwave spectroscopy. The water is hydrogen bonded to the nitrogen, as expected, but the hydrogen bond is bent, with the oxygen tilted toward either of the ortho hydrogens of the pyridine. This gives rise to a pair of equivalent configurations and the possibility of a tunneling motion involving an in-plane rocking of the water. DFT calculations support this view. Experimentally, a pair of states with severely perturbed rotational structure has been identified and the spectra assigned. Analysis of the perturbations in the a-type (pure rotation) spectra has enabled an accurate determination of the tunneling splitting, which has been confirmed by direct observation of b-type (rotation-tunneling) transitions. A simultaneous fit of the a- and b- type transitions gives the most accurate value of the tunneling splitting. Results for the H2O, D2O, and D-bound HOD complexes will be presented. The tunneling splittings are as follows: H2O-pyridine (10402.9 MHz), HOD-pyridine (12513.4 MHz, determined only from perturbation analysis), and D2O-pyridine (13582.3 MHz). Curiously, the tunneling splitting increases with increased deuteration. Additional small splittings have been observed in some transitions, indicating the possibility of further internal dynamics. This system offers an interesting test case for theoretical treatments of large amplitude motion.

  12. Pyrrolnitrin and related pyrroles endowed with antibacterial activities against Mycobacterium tuberculosis.

    PubMed

    Di Santo, R; Costi, R; Artico, M; Massa, S; Lampis, G; Deidda, D; Pompei, R

    1998-10-20

    During development of nitroheterocycles with potential antimycobacterial activities we have tested against Mycobacterium tuberculosis a number of pyrroles strictly related to pyrrolnitrin, an antifungal antibiotic isolated from Streptomyces pyrrocinia. Some of the tested arylpyrrole derivatives and pyrrolnitrin have shown appreciable inhibiting activity against M. tuberculosis and M. avium. SAR studies well correlate antimycobacterial potency with the presence of halogens in the phenyl ring and a nitro group at position 3 of pyrrole.

  13. Ultrafast internal conversion dynamics of highly excited pyrrole studied with VUV/UV pump probe spectroscopy

    NASA Astrophysics Data System (ADS)

    Horton, Spencer L.; Liu, Yusong; Chakraborty, Pratip; Matsika, Spiridoula; Weinacht, Thomas

    2017-02-01

    We study the relaxation dynamics of pyrrole after excitation with an 8 eV pump pulse to a state just 0.2 eV below the ionization potential using vacuum ultraviolet/ultraviolet pump probe spectroscopy. Our measurements in conjunction with electronic structure calculations indicate that pyrrole undergoes rapid internal conversion to the ground state in less than 300 fs. We find that internal conversion to the ground state dominates over dissociation.

  14. Indole Localization in an Explicit Bilayer Revealed via Molecular Dynamics

    NASA Astrophysics Data System (ADS)

    Norman, Kristen

    2005-11-01

    It is well known that the amino-acid tryptophan is particularly stable in the interfacial region of biological membranes, and this preference is a property of the tryptophan side-chain. Analogues of this side-chain, such as indole, strongly localize in the interfacial region, especially near the glycerol moiety of the lipids in the bilayer. Using molecular dynamics calculations, we determine the potential of mean force (PMF) for indoles in the bilayer. We compare the calculated PMF for indole with that of benzene to show that exclusion from the center of the lipid bilayer does not occur in all aromatics, but is strong in indoles. We find three minima in the PMF. Indole is most stabilized near the glycerol moiety. A weaker binding location is found near the choline groups of the lipid molecules. An even weaker binding side is found near the center of the lipid hydrocarbon core. Comparisions between uncharged, weakly charged, and highly charged indoles demonstrate that the exclusion is caused by the charge distribution on the indole rather than the ``lipo-phobic'' effect. High temperature simulations are used to determine the relative contribution of enthalpy and entropy to indole localization. The orientation of indole is found to be largely charge independent and is a strong function of depth within the bilayer. We find good agreement between simulated SCD order parameters for indole and experimentally determined order parameters.

  15. Indoles - A promising scaffold for drug development.

    PubMed

    Sravanthi, T V; Manju, S L

    2016-08-25

    Generally, heterocycles occupy a prominent place in chemistry due to their wide range of applications in the fields of drug design, photochemistry, agrochemicals, dyes and so on. Among them, indole scaffolds have been found in most of the important synthetic drug molecules and paved a faithful way to develop effective targets. Privileged structures bind to multiple receptors with high affinity, thus aiding the development of novel biologically active compounds. Among the indole class of compounds, 2-arylindoles appear to be a most promising lead for drug development. The derivatives of 2-arylindoles exhibits antibacterial, anticancer, anti-oxidants, anti-inflammatory, anti-diabetic, antiviral, antiproliferative, antituberculosis activity, etc. This article would provide a clear knowledge on the wide-ranging biological activities of 2-arylindoles over the past two decades, which would be beneficial for the designing of more potent drug targets in order to compete with the existing drugs. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. Obinutuzumab for the treatment of indolent lymphoma.

    PubMed

    Edelmann, Jennifer; Gribben, John G

    2016-08-01

    Obinutuzumab is a humanized, type II anti-CD20 monoclonal antibody designed for strong induction of direct cell death and antibody-dependent cell-mediated cytotoxicity. The Phase III GADOLIN trial tested the clinical efficacy of obinutuzumab plus bendamustine followed by obinutuzumab monotherapy in rituximab-refractory indolent non-Hodgkin lymphoma versus treatment with bendamustine alone. It demonstrated significantly longer progression-free survival for the obinutuzumab-containing regimen in this difficult to treat patient group. Based on the results of this trial, US FDA approval was most recently granted for obinutuzumab in the treatment of follicular lymphoma that has relapsed after or was refractory to a rituximab-containing regimen. This article summarizes the available data on chemistry, pharmacokinetics, clinical efficacy and safety of obinutuzumab in the treatment of indolent non-Hodgkin lymphoma.

  17. Effects of heteroatoms on aromatic pi-pi interactions: benzene-pyridine and pyridine dimer.

    PubMed

    Hohenstein, Edward G; Sherrill, C David

    2009-02-05

    Heteroatoms are found in many noncovalent complexes which are of biological importance. The effect of heteroatoms on pi-pi interactions is assessed via highly accurate quantum chemical computations for the two simplest cases of interactions between aromatic molecules containing heteroatoms, namely, benzene-pyridine and pyridine dimer. Benchmark quality estimated coupled-cluster through perturbative triples [CCSD(T)] binding energies are computed near the complete basis set limit. Comparisons to the benzene dimer are made to determine the contributions from heteroatoms. The presence of a heteroatom reduces the spatial extent of the pi-electron cloud and polarizability of pyridine as compared to benzene. As a result, the magnitude of the dispersion, exchange, and induction interactions in benzene-pyridine and pyridine dimer is generally reduced as compared to those for the benzene dimer. Benzene-pyridine and pyridine dimer bind more strongly than the benzene dimer in several configurations, and in contrast to the benzene dimer, parallel-displaced configurations can be significantly preferred over T-shaped configurations. Hydrogens para to a heteroatom are more effective "pi-hydrogen bond" donors, but aromatic rings with heteroatoms are worse "pi-hydrogen bond" acceptors.

  18. Molecular Characterization of Indolent Prostate Cancer

    DTIC Science & Technology

    2016-12-01

    reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing this collection of...feature of all human cancers at different stages of disease progression, we hypothesized that RNA and DNA alterations characteristic of indolent...Following review of our progress on the tasks outlined in SOW, we communicated to CDMRP our intention to request EWOF. On October 15th, 2015, this project

  19. New indole alkaloids from Sarcocephalus latifolius.

    PubMed

    Abreu, P; Pereira, A

    2001-01-01

    Phytochemical investigation of the root extract of Sarcocephalus latifolius has led to the isolation of the new indole alkaloids 21-O-methylstrictosamide aglycone and 21-O-ethylstrictosamide aglycone, together with strictosamide, angustine, nauclefine, angustidine, angustoline, 19-O-ethylangustoline, naucleidinal, 19-epi-naucleidinal, quinovic acid-3 beta-O-beta-D-fucopyranoside, quinovic acid-3 beta-O-alpha-L-rhamnopyranoside, scopoletin, and beta-sitosterol. Strictosamide displayed moderate antiplasmodial activity against Plasmodium falciparum.

  20. Motility-indole-lysine-sulfide medium.

    PubMed

    Ederer, G M; Lund, M E; Blazevic, D J; Reller, L B; Mirrett, S

    1975-09-01

    A medium designed for the detection of motility, indole, lysine decarboxylase and deaminase reactions, and H2S production was devised and evaluated. Results, using 157 strains of enteric pathogens, were in agreement with reference methods. When 300 isolates from fecal cultures were screened using this medium, Shigella was easily differentiated from Escherichia and more of the Proteus species, especially P. morganii, could be eliminated from further study.

  1. Unique monoterpenoid indole alkaloids from Alstonia scholaris.

    PubMed

    Cai, Xiang-Hai; Du, Zhi-Zhi; Luo, Xiao-Dong

    2007-04-26

    [structure: see text] A pair of geometrically isomeric monoterpenoid indole alkaloids with a skeleton rearrangement and two additional carbons, named (19,20) E-alstoscholarine (1) and (19,20) Z-alstoscholarine (2), were obtained from the leaf extract of Alstonia scholaris. Their structures were elucidated on the basis of spectroscopic methods and then confirmed by X-ray crystal diffraction. The biogenesis of these compounds was also proposed.

  2. Facile synthesis, structural elucidation and spectral analysis of pyrrole 4-imidazole derivatives

    NASA Astrophysics Data System (ADS)

    Singh, R. N.; Rawat, Poonam; Baboo, Vikas

    2015-12-01

    In this work pyrrole 4-imidazole derivatives (3A-3D): benzimidazoles and pyrrole 4-imidazoline have been synthesized by condensation, cyclization and oxidation of ethyl 4-formyl-3,5-dimethyl-1H-pyrrole carboxylate and phenylene diamine derivatives/ethylene diamine. The structure of these biheterocyclic compounds have been derived by elemental and spectroscopic - IR, UV, MS, 1H and 13C NMR analysis as well as theoretical study. The static first hyperpolarizability, β0 values for pyrrole 4-imidazole derivatives, (3A-3D) have been calculated as 10.901 × 10-31, 19.607 × 10-31, 40.323 × 10-31, 5.686 × 10-31 esu, respectively. The gradual increase in β0 value of synthesized pyrrole-benzimidazole derivatives from 3A to 3C is due to addition of acceptors -Cl atom in 3B to -NO2 group in 3C on benzimidazole side. The experimental absorption spectra found to be in UV region and the high β0 values show that the synthesized pyrrole-imidazoles are suitable as non-linear optical (NLO) materials.

  3. Calix[4]pyrroles: highly selective stationary phases for gas chromatographic separations.

    PubMed

    Fan, Jing; Wang, Zhenzhong; Li, Qian; Qi, Meiling; Shao, Shijun; Fu, Ruonong

    2014-10-03

    Calix[4]pyrroles offer a great potential as stationary phases for gas chromatography (GC) due to their unique structures and physicochemical properties. Herein we present the first report of using two calix[4]pyrroles, namely meso-tetra-cyclohexylcalix[4]pyrrole (THCP) and meso-octamethylcalix[4]pyrrole (OMCP). These stationary phases were statically coated onto capillary columns and investigated in terms of column efficiency, polarity, separation performance, thermal stability and repeatability. The columns achieved column efficiencies of 2200-3000plates/m and exhibited nonpolar nature with an average polarity of 67 for THCP and 64 for OMCP, respectively. THCP stationary phase shows high selectivity for analytes of different polarity and exhibits nice peak shapes, especially for aldehydes, alcohols and anilines that are prone to severe peak tailing in GC analysis. Interestingly, THCP stationary phase possesses superior resolving ability for aniline and benzenediol positional isomers while OMCP shows preferential selectivity for nonpolar analytes such as hexane isomers. Moreover, calix[4]pyrrole columns also have good thermal stability up to 260°C and repeatability with a relative standard deviation (RSD%) of less than 0.10% for run-to-run and less than 5.2% for column-to-column. This work demonstrates the unique separation performance of calix[4]pyrroles and their promising future as a new class of GC stationary phases. Copyright © 2014 Elsevier B.V. All rights reserved.

  4. Microwave spectrum and molecular constants of indole

    NASA Astrophysics Data System (ADS)

    Nesvadba, Radim; Studecký, Tomáš; Uhlíková, Tereza; Urban, Štěpán

    2017-09-01

    Every single person has a certain characteristic group of scent molecules. The microwave spectra of the organic compounds of scent could be useful for the identification of people, but a database of spectra of scent molecules needs to be created first. The spectrum of indole, that is among the human scent molecules, was measured in the frequency range of 7.5-19 GHz under the conditions of supersonic expansion in a pulse emission Fourier Transform Microwave Spectrometer (FTMW) with a Fabry-Perot resonator. The high resolution of the spectrometer enables the detection of rotational transitions with hyperfine splitting. A total of 37 new rotational transitions were measured and analyzed using the PGOPHER software to derive the rotational and centrifugal distortion constants, as well as the 14N nuclear quadrupole coupling constants. The molecular constants were determined with approximately two orders of magnitude greater accuracy as compared with some earlier studies of indole. The obtained data and constants of indole are the first step towards the development of a database of the human scent molecules.

  5. Sequence-selective single-molecule alkylation with a pyrrole-imidazole polyamide visualized in a DNA nanoscaffold.

    PubMed

    Yoshidome, Tomofumi; Endo, Masayuki; Kashiwazaki, Gengo; Hidaka, Kumi; Bando, Toshikazu; Sugiyama, Hiroshi

    2012-03-14

    We demonstrate a novel strategy for visualizing sequence-selective alkylation of target double-stranded DNA (dsDNA) using a synthetic pyrrole-imidazole (PI) polyamide in a designed DNA origami scaffold. Doubly functionalized PI polyamide was designed by introduction of an alkylating agent 1-(chloromethyl)-5-hydroxy-1,2-dihydro-3H-benz[e]indole (seco-CBI) and biotin for sequence-selective alkylation at the target sequence and subsequent streptavidin labeling, respectively. Selective alkylation of the target site in the substrate DNA was observed by analysis using sequencing gel electrophoresis. For the single-molecule observation of the alkylation by functionalized PI polyamide using atomic force microscopy (AFM), the target position in the dsDNA (∼200 base pairs) was alkylated and then visualized by labeling with streptavidin. Newly designed DNA origami scaffold named "five-well DNA frame" carrying five different dsDNA sequences in its cavities was used for the detailed analysis of the sequence-selectivity and alkylation. The 64-mer dsDNAs were introduced to five individual wells, in which target sequence AGTXCCA/TGGYACT (XY = AT, TA, GC, CG) was employed as fully matched (X = G) and one-base mismatched (X = A, T, C) sequences. The fully matched sequence was alkylated with 88% selectivity over other mismatched sequences. In addition, the PI polyamide failed to attach to the target sequence lacking the alkylation site after washing and streptavidin treatment. Therefore, the PI polyamide discriminated the one mismatched nucleotide at the single-molecule level, and alkylation anchored the PI polyamide to the target dsDNA.

  6. Riboflavin Production during Growth of Micrococcus luteus on Pyridine

    PubMed Central

    Sims, Gerald K.; O'Loughlin, Edward J.

    1992-01-01

    Micrococcus luteus produced 29 μM riboflavin during growth on 6.5 mM pyridine but not during growth on other substrates. On the basis of the results of radiolabelling studies, riboflavin was not directly synthesized from pyridine. Pyridine may interfere with riboflavin biosynthesis or elicit a general stress response in M. luteus. PMID:16348793

  7. Unprecedented Utilization of Pelargonidin and Indole for the Biosynthesis of Plant Indole Alkaloids.

    PubMed

    Warskulat, Anne-Christin; Tatsis, Evangelos C; Dudek, Bettina; Kai, Marco; Lorenz, Sybille; Schneider, Bernd

    2016-02-15

    Nudicaulins are a group of indole alkaloid glycosides responsible for the color of yellow petals of Papaver nudicaule (Iceland poppy). The unique aglycone scaffold of these alkaloids attracted our interest as one of the most unusual flavonoid-indole hybrid structures that occur in nature. Stable isotope labeling experiments with sliced petals identified free indole, but not tryptamine or l-tryptophan, as one of the two key biosynthetic precursors of the nudicaulin aglycone. Pelargonidin was identified as the second key precursor, contributing the polyphenolic unit to the nudicaulin molecule. This finding was inferred from the temporary accumulation of pelargonidin glycosides in the petals during flower bud development and a drop at the point in time when nudicaulin levels start to increase. The precursor-directed incorporation of cyanidin into a new 3'-hydroxynudicaulin strongly supports the hypothesis that anthocyanins are involved in the biosynthesis of nudicaulins.

  8. Unprecedented Utilization of Pelargonidin and Indole for the Biosynthesis of Plant Indole Alkaloids

    PubMed Central

    Warskulat, Anne‐Christin; Tatsis, Evangelos C.; Dudek, Bettina; Kai, Marco; Lorenz, Sybille

    2016-01-01

    Abstract Nudicaulins are a group of indole alkaloid glycosides responsible for the color of yellow petals of Papaver nudicaule (Iceland poppy). The unique aglycone scaffold of these alkaloids attracted our interest as one of the most unusual flavonoid‐indole hybrid structures that occur in nature. Stable isotope labeling experiments with sliced petals identified free indole, but not tryptamine or l‐tryptophan, as one of the two key biosynthetic precursors of the nudicaulin aglycone. Pelargonidin was identified as the second key precursor, contributing the polyphenolic unit to the nudicaulin molecule. This finding was inferred from the temporary accumulation of pelargonidin glycosides in the petals during flower bud development and a drop at the point in time when nudicaulin levels start to increase. The precursor‐directed incorporation of cyanidin into a new 3′‐hydroxynudicaulin strongly supports the hypothesis that anthocyanins are involved in the biosynthesis of nudicaulins. PMID:26670055

  9. Pyridine nucleotide coenzymes: Chemical, biological, and medical aspects. Vol. 2, Pt. A

    SciTech Connect

    Dolphin, D.; Poulson, R.; Avramovic, O.

    1987-01-01

    This text contains the following: History of the Pyridine Nucleotides Nomenclature; Evolution of Pyridine Nucleotide; Relationship Between Biosynthesis and Evolution; Crystal Structure; Coenzyme Conformations; Protein Interactions; Optical Spectroscopy of the Pyridine Nucleotides; Excited States of Pyridine Nucleotide Coenzymes; Fluorescence and Phosphorescence; Nuclear Magnetic Resonance Spectroscopy of Pyridine Nucleotides; Mass Spectrometry of Pyridine Nucleotides; Mechanism of Action of the Pyridine Nucleotides; Chemical Stability and Reactivity of Pyridine Nucleotide Coenzymes; Stereochemistry of Fatty Acid Biosynthesis and Metabolism; Kinetics of Pyridine Nucleotide-Utilizing Enzymes; Preparation and Properties of NAD and NADP Analogs; Model Studies and Biological Activity of Analogs; and Spin-Labeled Pyridine Nucleotide Derivatives.

  10. Copper-mediated cross-coupling-cyclization-oxidation: a one-pot reaction to construct polysubstituted pyrroles.

    PubMed

    Liu, Pei; Liu, Jin-ling; Wang, Heng-shan; Pan, Ying-ming; Liang, Hong; Chen, Zhen-Feng

    2014-05-14

    A novel and efficient procedure for the synthesis of polysubstituted pyrroles has been developed in this work. The polysubsituted pyrroles were synthesized directly from terminal alkenes, amines and β-keto esters through cross-coupling-cyclization-oxidation in the presence of a catalytic amount of cuprous chloride. This method provides a one-pot synthesis route from terminal alkenes to polysubstituted pyrroles for the first time and opens a new area in cuprous catalysis.

  11. Biological Exposure Indices of Pyrrole Adducts in Serum and Urine for Hazard Assessment of n-Hexane Exposure

    PubMed Central

    Yin, Hongyin; Zhang, Chunling; Guo, Ying; Shao, Xiaoying; Zeng, Tao; Zhao, Xiulan; Xie, Keqin

    2014-01-01

    Background Pyrrole adducts might be used as a biomarker for monitoring occupational exposure to n-hexane, but the Biological Exposure Indices of pyrrole adducts in serum and urine are still unknown. The current study was designed to investigate the biological exposure limit of pyrrole adducts for hazard assessment of n-hexane. Methods Male Wistar rats were given daily dose of 500, 1000, 1500, 2000, 4000 mg/kg bw n-hexane by gavage for 24 weeks. The levels of pyrrole adducts in serum and urine were determined at 8, 24 hours postdose once a week. The Biological Exposure Indices was evaluated by neurological evaluation and the levels of pyrrole adducts. The difference in pyrrole adducts formation between humans and rats were estimated by using in vitro test. Results Dose-dependent effects were observed between the doses of n-hexane and pyrrole adducts in serum and urine, and the levels of pyrrole adduct in serum and urine approached a plateau at week 4. There was a significantly negative correlation between the time to paralysis and the level of pyrrole adducts in serum and urine, while a positive correlation between gait score and levels of pyrrole adducts in serum and urine was observed. In vitro, pyrrole adducts formed in human serum was about two times more than those in rat serum at the same level of 2,5-HD. Conclusion It was concluded that the BEIs of pyrrole adducts in humans were 23.1±5.91 nmol/ml in serum 8 h postdose, 11.7±2.64 nmol/ml in serum 24 h postdose, 253.8±36.3 nmol/ml in urine 8 h postdose and 54.6±15.42 nmol/ml in urine 24 h postdose. PMID:24465904

  12. Indole-3-acetic acid in plant-microbe interactions.

    PubMed

    Duca, Daiana; Lorv, Janet; Patten, Cheryl L; Rose, David; Glick, Bernard R

    2014-07-01

    Indole-3-acetic acid (IAA) is an important phytohormone with the capacity to control plant development in both beneficial and deleterious ways. The ability to synthesize IAA is an attribute that many bacteria including both plant growth-promoters and phytopathogens possess. There are three main pathways through which IAA is synthesized; the indole-3-pyruvic acid, indole-3-acetamide and indole-3-acetonitrile pathways. This chapter reviews the factors that effect the production of this phytohormone, the role of IAA in bacterial physiology and in plant-microbe interactions including phytostimulation and phytopathogenesis.

  13. Electropolymerized Pyrrole-Based Conductive Polymeric Ionic Liquids and Their Application for Solid-Phase Microextraction.

    PubMed

    Devasurendra, Amila M; Zhang, Cheng; Young, Joshua A; Tillekeratne, L M Viranga; Anderson, Jared L; Kirchhoff, Jon R

    2017-07-26

    Pyrrole was covalently bonded to 1-methyl and 1-benzylimidazolium ionic liquids (ILs) via an N-substituted alkyl linkage to prepare electropolymerizable IL monomers with excellent thermal stability. The methylimidazolium IL, [pyrrole-C6MIm](+), was then electropolymerized on macro- and microelectrode materials to form conductive polymeric IL (CPIL)-modified surfaces. Electrochemical characterization of a 1.6 mm diameter Pt disk electrode modified with poly[pyrrole-C6MIm](+) demonstrated a selective uptake for an anionic redox probe while rejecting a cationic redox probe. Furthermore, electropolymerization of [pyrrole-C6MIm](+) doped with single-walled carbon nanotubes (SWNT) on 125 μm platinum wires produced 42 μm thick poly[pyrrole-C6MIm](+)/SWNT films compared to 17 μm in the absence of SWNT and 5 μm for the previously reported poly[thiophene-C6MIm](+) coatings. The poly[pyrrole-C6MIm](+)/SWNT films were prepared with reproducible thicknesses as well as thermal properties sufficient for high-temperature applications, such as solid-phase microextraction (SPME) with gas chromatographic analysis. The utilization of the CPIL sorbent materials in SPME experiments provided excellent extraction efficiencies and selectivity toward organic aromatic analytes. The CPIL sorbent coatings also yielded outstanding fiber-to-fiber reproducibility on the basis of extraction efficiencies and improved response for a range of analytes relative to commercial 100 μm poly(dimethylsiloxane) fibers when normalized for differences in film thickness. Poly[pyrrole-C6MIm](+) CPIL coatings doped with SWNT are therefore promising new sorbent materials for SPME analyses.

  14. Polyorganometallosiloxane-2- or -4-pyridine coatings

    DOEpatents

    Sugama, Toshifumi

    1997-01-01

    A new family of polyorganometallosiloxane-2- or -4-pyridine compounds are provided for corrosion resistant coatings on light metals such as aluminum, magnesium, zinc, steel and their allows. The novel compounds contain backbones modified by metal alkoxides, metallocenes and metallophthalocyanates where the metal is Zr, Ti, Mo, V, Hf, Nb, Si, B and combinations thereof. Methods of making the new compounds are also provided.

  15. Synthesis and reactivity of highly nucleophilic pyridines.

    PubMed

    De Rycke, Nicolas; Berionni, Guillaume; Couty, François; Mayr, Herbert; Goumont, Regis; David, Olivier R P

    2011-02-04

    3,4,5-Triamino-substituted pyridines are avid for electrophiles but are still willing to give them back. In these compounds three amino groups conjoin their forces into the heterocyclic nitrogen, making it a powerful Lewis base. A short and efficient synthesis is described, and the origin of its unique activity in nucleophilic organocatalysis is rationalized by kinetics and thermodynamic quantifications.

  16. Novel indolizino[8,7-b]indole hybrids as anti-small cell lung cancer agents: Regioselective modulation of topoisomerase II inhibitory and DNA crosslinking activities.

    PubMed

    Chang, Sue-Ming; Christian, Wilson; Wu, Ming-Hsi; Chen, Tai-Lin; Lin, Yi-Wen; Suen, Ching-Shu; Pidugu, Hima Bindu; Detroja, Dilip; Shah, Anamik; Hwang, Ming-Jing; Su, Tsann-Long; Lee, Te-Chang

    2017-02-15

    A novel series of bis(hydroxymethyl)indolizino[8,7-b]indole hybrids composed of β-carboline (topoisomerase I/II inhibition) and bis(hydroxymethyl)pyrrole (DNA cross-linking) are synthesized for antitumor evaluation. Of tumor cell lines tested, small cell lung cancer (SCLC) cell lines are the most sensitive to the newly synthesized compounds. These hybrids induce cell cycle arrest at the G2/M phase, trigger tumor cell apoptotic death, and display diverse mechanisms of action involving topoisomerase II (Topo II) inhibition and induction of DNA cross-linking. Intriguingly, the substituent at N(11) (H or Me) plays a critical role in modulating Topo II inhibition and DNA cross-linking activities. N(11)-Me derivatives predispose to induce DNA crosslinks, whereas N(11)-H derivatives potently inhibit Topo II. Computational analysis implicates that N(11)-Me restrict the torsion angles of the two adjacent OH on pyrrole resulting in a favorable of DNA cross-linking. Among these hybrids, compound 17a with N(11)-H is more effective than cisplatin and etoposide, but as potent as irinotecan, against the growth of SCLC H526 cells in xenograft model.

  17. Peroxynitrite scavenging activity of indole derivatives: interaction of indoles with peroxynitrite.

    PubMed

    Soung, Do Yu; Choi, Hye Rhi; Kim, Ji Young; No, Jae Kyung; Lee, Jee Hyun; Kim, Min Sun; Rhee, Sook Hee; Park, Jin Seng; Kim, Myung Jung; Yang, Ryung; Chung, Hae Young

    2004-01-01

    One of the products of nitrogen-derived free radicals, peroxynitrite (ONOO(-)), is formed by the reaction of superoxide anion (O(2)(*-)) with nitric oxide (NO). ONOO(-) can cause damage to proteins and DNA through nitration. In particular, proteins and their constituent amino acids have been proven to be extremely sensitive to ONOO(-). However, the lack of specific endogenous defense enzymes to protect against ONOO(-) has prompted many researchers to search for endogenous scavengers. We previously found 5-hydroxytryptamine (HT), which is an indole derivative (ID), to be an efficient ONOO(-) scavenger. In the present study, the interaction of several other indoles was further investigated: tryptophan (TRP), 5-hydroxyL-tryptophan (HLT), HT, N-acetyl-5-hydroxytryptamine (AHT), 5-methoxyindole-3-acetate (MIA), 5-methoxytryptamine (MT), and melatonin. The ONOO(-) scavenging activity of ID was assayed by measuring the formation of oxidized dihydrorhodamine-123 (DHR-123). The scavenging efficacy was expressed as the IC(50), denoting the concentration of each indole required to cause 50% inhibition of DHR-123 formation. In a separate in vitro study, the protective effect of IDs against ONOO(-)-induced nitration of bovine serum albumin was investigated. Nitration was quantified using an immunoassay with a monoclonal anti-nitrotyrosine antibody, and a horseradish peroxidase-conjugated anti-mouse secondary antibody from sheep. The results revealed that the inhibitory activities of indoles were as follows: HLT, IC(50) = 0.73 microM; HT, IC(50) = 1.03 microM; and AHT, IC(50) = 0.98 microM), showing relatively strong activities against ONOO(-). Interestingly, TRP, MIA, MT, and melatonin were less effective. Regarding the protection of albumin by IDs, the data showed that the formation of ONOO(-) was inhibited in a dose-dependent manner. Further probing of the mode of the interaction of indoles revealed that the hydroxyl groups in IDs are required for the enhanced scavenging

  18. Antitussive indole alkaloids from Kopsia hainanensis.

    PubMed

    Tan, Min-Jia; Yin, Chun; Tang, Chun-Ping; Ke, Chang-Qiang; Lin, Ge; Ye, Yang

    2011-06-01

    Three new indole alkaloids, named kopsihainins A-C (1-3), and two known compounds, kopsinine (4) and methyl demethoxycarbonylchanofruticosinate (5), were isolated from the stems of Kopsia hainanensis. Their structures were determined using extensive spectroscopic methods. The two main constituents 4 and 5 exhibited significant antitussive activity in a citric acid induced guinea pig cough model. The antitussive effect of 4 was demonstrated to interact with the δ-opioid receptor. This is the first report of antitussive effects of aspidofractinine type and chanofruticosinate type alkaloids. © Georg Thieme Verlag KG Stuttgart · New York.

  19. Organic-inorganic interactions in the system of pyrrole-hematite-water at elevated temperatures and pressures

    NASA Astrophysics Data System (ADS)

    Ding, Kangle

    2015-11-01

    The distribution and abundance of pyrrolic compounds in sediments and crude oils are most likely influenced by inorganic sedimentary components. In this paper, thermal simulation experiments on the system pyrrole-hematite-water were carried out at elevated temperatures and pressures in order to investigate the effect of organic-inorganic interactions on the preservation of pyrrolic compounds. Compositions of the reaction products were analyzed with GC-MS and GC-FID methods. In the closed system pyrrole-hematite-water, the nitrogen-oxygen exchange obviously occurred at temperatures above 350ºC in accordance with the thermochemical calculation. Large amounts of furan and ammonia were generated after simulation experiments, indicating that the conversion of pyrrole into furan was the dominant reaction. Thermochemical exchange effect between organic nitrogen and inorganic oxygen was obviously facilitated by elevated temperatures and found to be catalyzed by hematite, but inhibited by the increasing volume of water. Thermodynamically water spontaneously reacts with pyrrole above 300ºC. The reaction of pyrrole-hematite-water is an exothermic process in which the reaction heat positively correlates with temperature. The heat released was estimated as 9.0 KJ/(mol) pyrrole - 15.0 KJ/(mol) pyrrole in typical oil reservoirs (100ºC-150ºC) and 15.0-23.0 KJ/(mol) pyrrole in typical gas reservoirs (150ºC-200ºC). The calculated activation energy of the nitrogen-oxygen atom exchange is about 129.59 kJ/mol. According to the experimental results, a small amount of water may effectively initiate the nitrogen-oxygen exchange. The study would improve our evaluating of the preservation and fate of pyrrolic compounds in deeply buried geologic settings and further understanding of thermochemical processes behind the degradation of petroleum.

  20. Electrophilic surface sites as precondition for the chemisorption of pyrrole on GaAs(001) surfaces

    SciTech Connect

    Bruhn, Thomas; Fimland, Bjørn-Ove; Vogt, Patrick

    2015-03-14

    We report how the presence of electrophilic surface sites influences the adsorption mechanism of pyrrole on GaAs(001) surfaces. For this purpose, we have investigated the adsorption behavior of pyrrole on different GaAs(001) reconstructions with different stoichiometries and thus different surface chemistries. The interfaces were characterized by x-ray photoelectron spectroscopy, scanning tunneling microscopy, and by reflectance anisotropy spectroscopy in a spectral range between 1.5 and 5 eV. On the As-rich c(4 × 4) reconstruction that exhibits only nucleophilic surface sites, pyrrole was found to physisorb on the surface without any significant modification of the structural and electronic properties of the surface. On the Ga-rich GaAs(001)-(4 × 2)/(6 × 6) reconstructions which exhibit nucleophilic as well as electrophilic surface sites, pyrrole was found to form stable covalent bonds mainly to the electrophilic (charge deficient) Ga atoms of the surface. These results clearly demonstrate that the existence of electrophilic surface sites is a crucial precondition for the chemisorption of pyrrole on GaAs(001) surfaces.

  1. Synthesis, spectroscopic analysis and theoretical study of new pyrrole-isoxazoline derivatives

    NASA Astrophysics Data System (ADS)

    Rawat, Poonam; Singh, R. N.; Baboo, Vikas; Niranjan, Priydarshni; Rani, Himanshu; Saxena, Rajat; Ahmad, Sartaj

    2017-02-01

    In the present work, we have efficiently synthesized the pyrrole-isoxazoline derivatives (4a-d) by cyclization of substituted 4-chalconylpyrrole (3a-d) with hydroxylamine hydrochloride. The reactivity of substituted 4-chalconylpyrrole (3a-d), towards nucleophiles hydroxylamine hydrochloride was evaluated on the basis of electrophilic reactivity descriptors (fk+, sk+, ωk+) and they were found to be high at unsaturated β carbon of chalconylpyrrole indicating its more proneness to nucleophilic attack and thereby favoring the formation of reported new pyrrole-isoxazoline compounds (4a-d). The structures of newly synthesized pyrrole-isoxazoline derivatives were derived from IR, 1H NMR, Mass, UV-Vis and elemental analysis. All experimental spectral data corroborate well with the calculated spectral data. The FT-IR analysis shows red shifts in vN-H and vC = O stretching due to dimer formation through intermolecular hydrogen bonding. On basis set superposition error correction, the intermolecular interaction energy for (4a-d) is found to be 10.10, 9.99, 10.18, 11.01 and 11.19 kcal/mol respectively. The calculated first hyperpolarizability (β0) values of (4a-d) molecules are in the range of 7.40-9.05 × 10-30 esu indicating their suitability for non-linear optical (NLO) applications. Experimental spectral results, theoretical data, analysis of chalcone intermediates and pyrrole-isoxazolines find usefulness in advancement of pyrrole-azole chemistry.

  2. Contribution of phospholipid pyrrolization to the color reversion produced during deodorization of poorly degummed vegetable oils.

    PubMed

    Zamora, Rosario; Olmo, Carmen; Navarro, José L; Hidalgo, Francisco J

    2004-06-30

    The Ehrlich reaction was optimized to determine the formation of pyrrolized phospholipids in edible oils in an attempt to understand the color reversion produced during the deodorization of poorly degummed edible oils. The procedure consisted of the treatment of the oil with p-(dimethylamino)benzaldehyde in tetrahydrofuran/2-propanol at a controlled acidity and temperature and the spectrophotometric determination of adducts produced. The extinction coefficient of Ehrlich adducts was calculated by using 1-[1-(2-hydroxyethyl)-1H-pyrrol-2-yl]propan-1-ol (1) as a standard and was 15 300 M(-)(1) cm(-)(1). The response was linear and reproducible within the range of 0.334-48.6 microM of compound 1. When the assay was applied to a soybean oil treated with 100-1000 ppm of phosphatidylethanolamine and submitted to deodorization, the formation of pyrrolized phospholipids was observed at the same time that the disappearance of the phospholipid and the oil darkening were produced. The main changes were observed during the first steps of the deodorization process, when the oil was heated between 80 and 160 degrees C. During the initial heating of the oil until achieving 200 degrees C, oil darkening, phosphatidylethanolamine disappearance, and pyrrolized phospholipid formation were correlated, therefore suggesting a contribution of phospholipid pyrrolization to the oil darkening produced.

  3. Structural Studies of Pyrrole-Benzene Complexes by Chirped-Pulse Rotational Spectroscopy

    NASA Astrophysics Data System (ADS)

    Lobsiger, Simon; Perez, Cristobal; Zaleski, Daniel P.; Seifert, Nathan A.; Pate, Brooks H.; Pfaffen, Chantal; Trachsel, Maria A.; Leutwyler, Samuel

    2013-06-01

    Non-covalent intermolecular interactions are important in structural biology. The N-H \\cdots π hydrogen bond between amino acid side chains is an important structural determinant and highly affects the secondary structure of proteins. The pyrrole-benzene complex can be viewed as a model system for studying these fundamental interactions. Previous IR and UV spectroscopic studies of the pyrrole-benzene complex by Dauster et al. support a T-shaped structure with an N-H \\cdots π hydrogen bond to the benzene ring. In order to obtain accurate structural information we have investigated the broadband rotational spectrum of the supersonic-jet cooled complexes of pyrrole with benzene and benzene-d_{1} in the 2-18 GHz frequency range. In addition to the hetero dimer we have also observed the two cyclic mixed trimers (pyrrole)_{2}-benzene and pyrrole-(benzene)_{2}. I. Dauster, C. A. Rice, P. Zielke, and M. A. Suhm Phys. Chem. Chem. Phys. {10}, 2827 (2008) C. Pfaffen, D. Infanger, P. Ottiger, H. M. Frey, and S. Leutwyler Phys. Chem. Chem. Phys. {13}, 14110 (2011)

  4. Identification of New Metabolites of Bacterial Transformation of Indole by Gas Chromatography-Mass Spectrometry and High Performance Liquid Chromatography

    PubMed Central

    Arora, Pankaj Kumar

    2014-01-01

    Arthrobacter sp. SPG transformed indole completely in the presence of an additional carbon source. High performance liquid chromatography and gas chromatography-mass spectrometry detected indole-3-acetic acid, indole-3-glyoxylic acid, and indole-3-aldehyde as biotransformation products. This is the first report of the formation of indole-3-acetic acid, indole-3-glyoxylic acid, and indole-3-aldehyde from indole by any bacterium. PMID:25548566

  5. Enzymic synthesis of indol-3-ylacetyl-myo-inositol galactoside.

    PubMed

    Corcuera, L J; Michalczuk, L; Bandurski, R S

    1982-11-01

    Extracts of immature kernels of Zea mays catalysed the synthesis of indol-3-ylacetyl-myo-inositol galactoside from indol-3-ylacetyl-myo-inositol and UDP-galactose. Addition of 2-mercaptoethanol was required for stability of the catalytic activity during dialysis. The enzyme could be fractionated with (NH4)2SO4, and 55% of the activity was recovered in the 30-60%-saturation fraction. The product of the reaction contained radioactivity from UDP-[U-14C]galactose and was identified as indol-3-ylacetyl-myo-inositol galactoside by gas chromatography-mass spectrometry. Therefore a UDP-galactose:indol-3-ylacetyl-myo-inositol galactosyltransferase (indol-3-ylacetyl-myo-inositol galactoside synthase) is present in developing kernels of Zea mays. The description of this enzyme, together with the enzymes described in the accompanying paper [Michalczuk & Bandurski (1982) Biochem. J. 207, 273-281] for the synthesis of indol-3-ylacetylglucose and indol-3-ylacetyl-myo-inositol, now provides mechanisms for the biosynthesis of one-half of the low-molecular-weight esters of indol-3-ylacetic acid in Zea mays.

  6. Combined 3D-QSAR modeling and molecular docking studies on pyrrole-indolin-2-ones as Aurora A kinase inhibitors.

    PubMed

    Ai, Yong; Wang, Shao-Teng; Sun, Ping-Hua; Song, Fa-Jun

    2011-01-01

    Aurora kinases have emerged as attractive targets for the design of anticancer drugs. 3D-QSAR (comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA)) and Surflex-docking studies were performed on a series of pyrrole-indoline-2-ones as Aurora A inhibitors. The CoMFA and CoMSIA models using 25 inhibitors in the training set gave r(2) (cv) values of 0.726 and 0.566, and r(2) values of 0.972 and 0.984, respectively. The adapted alignment method with the suitable parameters resulted in reliable models. The contour maps produced by the CoMFA and CoMSIA models were employed to rationalize the key structural requirements responsible for the activity. Surflex-docking studies revealed that the sulfo group, secondary amine group on indolin-2-one, and carbonyl of 6,7-dihydro-1H-indol-4(5H)-one groups were significant for binding to the receptor, and some essential features were also identified. Based on the 3D-QSAR and docking results, a set of new molecules with high predicted activities were designed.

  7. Combined 3D-QSAR Modeling and Molecular Docking Studies on Pyrrole-Indolin-2-ones as Aurora A Kinase Inhibitors

    PubMed Central

    Ai, Yong; Wang, Shao-Teng; Sun, Ping-Hua; Song, Fa-Jun

    2011-01-01

    Aurora kinases have emerged as attractive targets for the design of anticancer drugs. 3D-QSAR (comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA)) and Surflex-docking studies were performed on a series of pyrrole-indoline-2-ones as Aurora A inhibitors. The CoMFA and CoMSIA models using 25 inhibitors in the training set gave r2cv values of 0.726 and 0.566, and r2 values of 0.972 and 0.984, respectively. The adapted alignment method with the suitable parameters resulted in reliable models. The contour maps produced by the CoMFA and CoMSIA models were employed to rationalize the key structural requirements responsible for the activity. Surflex-docking studies revealed that the sulfo group, secondary amine group on indolin-2-one, and carbonyl of 6,7-dihydro-1H-indol-4(5H)-one groups were significant for binding to the receptor, and some essential features were also identified. Based on the 3D-QSAR and docking results, a set of new molecules with high predicted activities were designed. PMID:21673910

  8. Antifungal Indole Alkaloids from Winchia calophylla.

    PubMed

    Yang, Mei-Li; Chen, Jia; Sun, Meng; Zhang, Dong-Bo; Gao, Kun

    2016-05-01

    Ten indole alkaloids (1-10) were obtained from an antifungal extract of Winchia calophylla, of which two (2 and 4) were new. N(4)-Methyl-10-hydroxyl-desacetylakuammilin (2) was an akuammiline-type indole alkaloid. N(1)-Methyl-echitaminic acid (4) was an unusual zwitterion with a basic vincorine-type skeleton. This is the first report of 10 in W. calophylla. The structures of all of the compounds were determined based on spectroscopic data, and their bioactivities were assessed. Compound 1 showed potent activity against the plant pathogenic fungi of Penicillium italicum and Fusarium oxysporum f.sp cubens with IC50 s of 10.4 and 11.5 µM, respectively, and 3 inhibited Rhizoctonia solani with an IC50 of 11.7 µM. Compounds 2 and 4 showed weak cytotoxicity against the human leukemic cell line HL-60 in vitro with IC50 s of 51.4 and 75.3 µM, respectively. Compounds 1 and 2 displayed weak activity against acetylcholinesterase with IC50 s around 61.3 and 52.6 µM, respectively.

  9. Chemoselective and Enantioselective Oxidation of Indoles Employing Aspartyl Peptide Catalysts

    PubMed Central

    Kolundzic, Filip; Noshi, Mohammad N.; Tjandra, Meiliana; Movassaghi, Mohammad; Miller, Scott J.

    2011-01-01

    Catalytic enantioselective indole oxidation is a process of particular relevance to the chemistry of complex alkaloids, as it has been implicated in their biosynthesis. In the context of synthetic methodology, catalytic enantioselective indole oxidation allows a rapid and biomimetic entry into several classes of alkaloid natural products. Despite this potentially high utility in the total synthesis, reports of catalytic enantioselective indole oxidation remain sparse. Here we report a highly chemoselective catalytic system for the indole oxidation that delivers 3-hydroxy-indolenines with good chemical yields and moderate to high levels of enantio- and diastereoselectivity (up to 95:5 er and up to 92:8 dr. These results represent, to our knowledge, the most selective values yet reported in the literature for catalytic asymmetric indole oxidation). Furthermore, the utility of enantioenriched hydroxy-indolenines in stereospecific rearrangements is demonstrated. PMID:21539386

  10. The gene controlling the indole glucosinolate modifier1 quantitative trait locus alters indole glucosinolate structures and aphid resistance in Arabidopsis.

    PubMed

    Pfalz, Marina; Vogel, Heiko; Kroymann, Juergen

    2009-03-01

    Glucosinolates are defensive secondary compounds that display large structural diversity in Arabidopsis thaliana and related plants. Much attention has been paid to variation in the biosynthesis of Met-derived aliphatic glucosinolates and its ecological consequences, but little is known about the genes that cause qualitative and quantitative differences in Trp-derived indole glucosinolates. We use a combination of quantitative trait locus (QTL) fine-mapping and microarray-based transcript profiling to identify CYP81F2 (At5g57220), encoding a cytochrome P450 monooxygenase, as the gene underlying Indole Glucosinolate Modifier1 (IGM1), a metabolic QTL for the accumulation of two modified indole glucosinolates, 4-hydroxy-indole-3-yl-methyl and 4-methoxy-indole-3-yl-methyl glucosinolate. We verify CYP81F2 function with two SALK T-DNA insertion lines and show that CYP81F2 catalyzes the conversion of indole-3-yl-methyl to 4-hydroxy-indole-3-yl-methyl glucosinolate. We further show that the IGM1 QTL is largely caused by differences in CYP81F2 expression, which results from a combination of cis- and trans-acting expression QTL different from known regulators of indole glucosinolate biosynthesis. Finally, we elucidate a potential function of CYP81F2 in plant-insect interactions and find that CYP81F2 contributes to defense against the green peach aphid (Myzus persicae) but not to resistance against herbivory by larvae from four lepidopteran species.

  11. Synthesis and optical and electrochemical properties of julolidine-structured pyrido[3,4-b]indole dye.

    PubMed

    Enoki, Toshiaki; Matsuo, Keishi; Ohshita, Joji; Ooyama, Yousuke

    2017-02-01

    The julolidine-structured pyrido[3,4-b]indole dye ET-1 has been newly designed and developed as a small D-A fluorescent dye. ET-1 showed bathochromic shifts of the fluorescence band upon changing from aprotic solvents to protic solvents, as well as positive fluorescence solvatochromism. Moreover, it was found that ET-1 can form a 1 : 1 Py(N)-B complex with boron trifluoride and a hydrogen-bonded proton transfer (Py(N)-H) complex with trifluoroacetic acid, which exhibit photoabsorption and fluorescence bands at a longer wavelength region than the pristine ET-1. Based on optical (photoabsorption and fluorescence spectroscopy) and electrochemical (cyclic voltammetry) measurements, Lippert-Mataga plots, (1)H NMR spectral measurement and density functional theory (DFT) calculation, this work indicated that the Py(N)-B complex or the Py(N)-H complex is effectively formed and stable in solution. This is due to the strong Py(N)-B interaction or Py(N)-hydrogen-bond, which can be attributed to the enhanced basicity or the accumulated electron density on the nitrogen atom of the pyridine ring caused by the introduction of a julolidine (quinolizidine) moiety as a strong electron-donating group. We propose that the D-A-type dye ET-1 based on the julolidine-structured pyrido[3,4-b]indole possesses the ability to act as a calorimetric and fluorescent sensor for Brønsted and Lewis acids.

  12. From ergolines to indoles: improved inhibitors of the human H3 receptor for the treatment of narcolepsy.

    PubMed

    Auberson, Yves P; Troxler, Thomas; Zhang, Xuechun; Yang, Charles R; Feuerbach, Dominik; Liu, Yu-Chih; Lagu, Bharat; Perrone, Mark; Lei, Lijun; Shen, Xiaoxia; Zhang, Dushan; Wang, Chunxiu; Wang, Tie-Lin; Briner, Karin; Bock, Mark G

    2015-02-01

    Ergolines were recently identified as a novel class of H3 receptor (H3R) inverse agonists. Although their optimization led to drug candidates with encouraging properties for the treatment of narcolepsy, brain penetration remained low. To overcome this issue, ergoline 1 ((6aR,9R,10aR)-4-(2-(dimethylamino)ethyl)-N-phenyl-9-(pyrrolidine-1-carbonyl)-6,6a,8,9,10,10a-hexahydroindolo[4,3-fg]quinoline-7(4H)-carboxamide)) was transformed into a series of indole derivatives with high H3R affinity. These new molecules were profiled by simultaneous determination of their brain receptor occupancy (RO) levels and pharmacodynamic (PD) effects in mice. These efforts culminated in the discovery of 15 m ((R)-1-isopropyl-5-(1-(2-(2-methylpyrrolidin-1-yl)ethyl)-1H-indol-4-yl)pyridin-2(1H)-one), which has an ideal profile showing a strong correlation of PD effects with RO, and no measurable safety liabilities. Its desirably short duration of action was confirmed by electroencephalography (EEG) measurements in rats.

  13. N-pyridinyl-indole-3-(alkyl)carboxamides and derivatives as potential systemic and topical inflammation inhibitors.

    PubMed

    Duflos, M; Nourrisson, M R; Brelet, J; Courant, J; LeBaut, G; Grimaud, N; Petit, J Y

    2001-06-01

    N-substituted-(indol-3-yl)carboxamides 10-15 and alkanamides 16-18 were prepared starting from the corresponding acids and submitted to screening for evaluation of their anti-inflammatory activity. None of the considered carboxamides exhibited significant inhibitory effect in the carrageenin-induced rat paw oedema after oral administration of 0.1 mM x kg(-1); nevertheless introduction of an alkyl chain, leading to alkanamides 16-18, induced moderate to high activity: 46-95% inhibition. The efficacy of these compounds in the inhibition of topical inflammation was confirmed by measuring reduction of ear thickness in the acute tetradecanoyl phorbol acetate (TPA)-induced mouse ear swelling assay. Preliminary pharmacomodulation brought to the fore that toxic effects induced, at 0.4 mM x kg(-1), by N-(pyridin-4-yl)(indol-3-yl)propanamide (17) could be attenuated or suppressed by 5-fluorination or introduction of a methoxycarbonylborane moiety, leading to 18 and 21.

  14. One-pot Unsymmetrical Ketone Synthesis Employing a Pyrrole-Bearing Formal Carbonyl Dication Linchpin Reagent.

    PubMed

    Heller, Stephen T; Newton, James N; Fu, Tingting; Sarpong, Richmond

    2015-08-17

    A one-pot procedure for the synthesis of unsymmetrical ketones utilizing a pyrrole-bearing carbonyl linchpin reagent (carbonyl linchpin N,O-dimethylhydroxylamine pyrrole; CLAmP) is reported. In contrast to other carbonyl dielectrophile equivalents, CLAmP enables the synthesis of ketones from a variety of organolithium and Grignard reagents. The electrophilic nature of CLAmP enables the addition of less reactive as well as thermally unstable nucleophiles. CLAmP was designed to form kinetically stable tetrahedral intermediates upon the addition of organometallic nucleophiles. Evidence for the existence of persistent tetrahedral intermediates was obtained through in situ IR studies.

  15. Octahydropyrrolo[3,4-c]pyrrole negative allosteric modulators of mGlu1

    PubMed Central

    Manka, Jason T.; Rodriguez, Alice L.; Morrison, Ryan D.; Venable, Daryl F.; Cho, Hyekyung P.; Blobaum, Anna L.; Daniels, J. Scott; Niswender, Colleen M.; Conn, P. Jeffrey; Lindsley, Craig W.; Emmitte, Kyle A.

    2014-01-01

    Development of SAR in an octahydropyrrolo[3,4-c]pyrrole series of negative allosteric modulators of mGlu1 using a functional cell-based assay is described in this Letter. The octahydropyrrolo[3,4-c]pyrrole scaffold was chosen as an isosteric replacement for the piperazine ring found in the initial hit compound. Characterization of selected compounds in protein binding assays was used to identify the most promising analogs, which were then profiled in P450 inhibition assays in order to further assess the potential for drug-likeness within this series of compounds. PMID:23932792

  16. Polyorganometallosiloxane-2- or -4-pyridine coatings

    DOEpatents

    Sugama, T.

    1997-12-30

    A new family of polyorganometallosiloxane-2- or -4-pyridine compounds are provided for corrosion resistant coatings on light metals such as aluminum, magnesium, zinc, steel and their alloys. The novel compounds contain backbones modified by metal alkoxides, metallocenes and metallophthalocyanates where the metal is Zr, Ti, Mo, V, Hf, Nb, Si, B and combinations thereof. Methods of making the new compounds are also provided. 13 figs.

  17. Thermometric titration of acids in pyridine.

    PubMed

    Vidal, R; Mukherjee, L M

    1974-04-01

    Thermometric titration of HClO(4), HI, HNO(3), HBr, picric acid o-nitrobenzoic acid, 2,4- and 2,5-dinitrophenol, acetic acid and benzoic acid have been attempted in pyridine as solvent, using 1,3-diphenylguanidine as the base. Except in the case of 2,5-dinitrophenol, acetic acid and benzoic acid, the results are, in general, reasonably satisfactory. The approximate molar heats of neutralization have been calculated.

  18. Reactions of halogen-pyridine systems

    SciTech Connect

    Coury, A.J.; Cahalan, P.T.

    1980-01-01

    The combination of halogens (acceptors) with pyridine derivatives (donors) produces, initially, charge transfer complexes with conductivities useful as depolarizers in lithium-halogen power cell cathodes. The complex most often employed in pacemaker batteries is I/sub 2//P2VP. Pyridines and halogens undergo additional reactions of consequence to cell performance. Such side reactions include: Alkyl group substitution, ring coupling, polymer molecular weight degradation, olefin addition and ring substitution. Instrumental analysis of model systems and the commercial iodine/poly-2-vinylpyridine (I/sub 2//P2VP) system provided evidence for alkyl group substitution, coupling and molecular weight degradation. The addition reaction was inferred from the presence of the needed reactants and their facile reactivity. Halogenation of the pyridine ring was not found. Side reactions cause reduced cathode capacity. Hydrogen halides generated by such side reactions may cause corrosion, but may enhance conductivity properties. Deleterious pressure buidup or dimensional changes may result from side reactions occurring within sealed battery cans. 7 refs.

  19. Effect of acceptor heteroatoms on π-hydrogen bonding interactions: a study of indole···thiophene heterodimer in a supersonic jet.

    PubMed

    Kumar, Sumit; Das, Aloke

    2012-09-07

    Resonant two photon ionization (R2PI), IR-UV, and UV-UV double resonance spectroscopic techniques combined with quantum chemistry calculations have been used to determine the structure of indole···thiophene dimer observed in a supersonic jet. With the help of combined experimental and theoretical IR spectra it has been found that the observed dimer has a N-H···π hydrogen bonded slanted T-shaped structure. The present study demonstrates the effect of heteroatoms present in the acceptors on the strength of the π-hydrogen bonding interactions. It was concluded by Sherrill and co-workers from their theoretical study of benzene···pyridine dimer that aromatic rings containing heteroatoms are poorest π-hydrogen bond acceptors [E. G. Hohenstein and C. D. Sherrill, J. Phys. Chem. A 113, 878 (2009)]. But the current spectroscopic investigation exhibits that five membered aromatic heterocycles are favorable π-hydrogen bond acceptors. In this study, it has also been shown that thiophene is a better π-hydrogen bond acceptor than furan. The present work has immense biological significance as indole is the chromophore of tryptophan residue in the proteins and thiophene derivatives have potential therapeutic applications. Thus, understanding the binding motif between indole and thiophene in the heterodimer studied in this work may help in designing efficient drugs.

  20. Indole and 7-hydroxyindole diminish Pseudomonas aeruginosa virulence.

    PubMed

    Lee, Jintae; Attila, Can; Cirillo, Suat L G; Cirillo, Jeffrey D; Wood, Thomas K

    2009-01-01

    Indole is an extracellular biofilm signal for Escherichia coli, and many bacterial oxygenases readily convert indole to various oxidized compounds including 7-hydroxyindole (7HI). Here we investigate the impact of indole and 7HI on Pseudomonas aeruginosa PAO1 virulence and quorum sensing (QS)-regulated phenotypes; this strain does not synthesize these compounds but degrades them rapidly. Indole and 7HI both altered extensively gene expression in a manner opposite that of acylhomoserine lactones; the most repressed genes encode the mexGHI-opmD multidrug efflux pump and genes involved in the synthesis of QS-regulated virulence factors including pyocyanin (phz operon), 2-heptyl-3-hydroxy-4(1H)-quinolone (PQS) signal (pqs operon), pyochelin (pch operon) and pyoverdine (pvd operon). Corroborating these microarray results, indole and 7HI decreased production of pyocyanin, rhamnolipid, PQS and pyoverdine and enhanced antibiotic resistance. In addition, indole affected the utilization of carbon, nitrogen and phosphorus, and 7HI abolished swarming motility. Furthermore, 7HI reduced pulmonary colonization of P. aeruginosa in guinea pigs and increased clearance in lungs. Hence, indole-related compounds have potential as a novel antivirulence approach for the recalcitrant pathogen P. aeruginosa.

  1. Glucose enhances indolic glucosinolate biosynthesis without reducing primary sulfur assimilation

    PubMed Central

    Miao, Huiying; Cai, Congxi; Wei, Jia; Huang, Jirong; Chang, Jiaqi; Qian, Hongmei; Zhang, Xin; Zhao, Yanting; Sun, Bo; Wang, Bingliang; Wang, Qiaomei

    2016-01-01

    The effect of glucose as a signaling molecule on induction of aliphatic glucosinolate biosynthesis was reported in our former study. Here, we further investigated the regulatory mechanism of indolic glucosinolate biosynthesis by glucose in Arabidopsis. Glucose exerted a positive influence on indolic glucosinolate biosynthesis, which was demonstrated by induced accumulation of indolic glucosinolates and enhanced expression of related genes upon glucose treatment. Genetic analysis revealed that MYB34 and MYB51 were crucial in maintaining the basal indolic glucosinolate accumulation, with MYB34 being pivotal in response to glucose signaling. The increased accumulation of indolic glucosinolates and mRNA levels of MYB34, MYB51, and MYB122 caused by glucose were inhibited in the gin2-1 mutant, suggesting an important role of HXK1 in glucose-mediated induction of indolic glucosinolate biosynthesis. In contrast to what was known on the function of ABI5 in glucose-mediated aliphatic glucosinolate biosynthesis, ABI5 was not required for glucose-induced indolic glucosinolate accumulation. In addition, our results also indicated that glucose-induced glucosinolate accumulation was due to enhanced sulfur assimilation instead of directed sulfur partitioning into glucosinolate biosynthesis. Thus, our data provide new insights into molecular mechanisms underlying glucose-regulated glucosinolate biosynthesis. PMID:27549907

  2. [Evaluation of antimicrobial activity of indol alkaloids].

    PubMed

    Rojas Hernández, N M

    1979-01-01

    In pursuing the study of the antimicrobial properties of alkaloids prepared from Cuban plants the activity of 10 indol alkaloids and 4 semisynthetic variables obtained from three plants--Catharanthus roseus G. Don., Vallesia antillana Wood and Ervatamia coronaria Staph, of the family Apocynaceae--growing in Cuba was assessed in vitro. The alkaloids and the variables used were catharantine, vindoline, vindolinine, perivine, reserpine, tabernaemontanine, tetrahydroalstonine, aparicine, vindolinic acid, reserpic acid and vindolininol. These were faced to 40 bacterial strains from the genera Salmonella, Shigella, Proteus, Escherichia, Pseudomonas, Staphylococcus and Corynebacterium as well as to fungi and yeasts from the genera Aspergillus, kCunnighamella, kCandida and Saccharomyces. The method involving cylindric sections in a double agar layer was applied and lectures were obtained at 24-48 hours of incubation at 25 degrees C for fungi and yeasts and 37 degrees C for bacteria. Inhibition zones are reported in millimeters.

  3. Strongly Acidic Auxin Indole-3-Methanesulfonic Acid

    PubMed Central

    Cohen, Jerry D.; Baldi, Bruce G.; Bialek, Krystyna

    1985-01-01

    A radiochemical synthesis is described for [14C]indole-3-methanesulfonic acid (IMS), a strongly acidic auxin analog. Techniques were developed for fractionation and purification of IMS using normal and reverse phase chromatography. In addition, the utility of both Fourier transform infrared spectrometry and fast atom bombardment mass spectrometry for analysis of IMS has been demonstrated. IMS was shown to be an active auxin, stimulating soybean hypocotyl elongation, bean first internode curvature, and ethylene production. IMS uptake by thin sections of soybean hypocotyl was essentially independent of solution pH and, when applied at a 100 micromolar concentration, IMS exhibited a basipetal polarity in its transport in both corn coleoptile and soybean hypocotyl sections. [14C]IMS should, therefore, be a useful compound to study fundamental processes related to the movement of auxins in plant tissues and organelles. PMID:16664007

  4. Schiff Bases of Benzothiazol-2-ylamine and Thiazolo[5,4-b] pyridin-2-ylamine as Anticonvulsants: Synthesis, Characterization and Toxicity Profiling.

    PubMed

    Shukla, Rashmi; Singh, Ajeet P; Sonar, Pankaj K; Mishra, Mudita; Saraf, Shailendra K

    2016-01-01

    Schiff bases have a broad spectrum of biological activities like antiinflammatory, analgesic, antimicrobial, anticonvulsant, antitubercular, anticancer, antioxidant, anthelmintic and so forth. Thus, after a thorough perusal of literature, it was decided to conjugate benzothiazol-2-ylamine/thiazolo [5, 4-b] pyridin-2-ylamine with aromatic and heteroaromatic aldehydes to get a series of Schiff bases. Synthesis, characterization, in-silico toxicity profiling and anticonvulsant activity of the Schiff bases of Benzothiazol-2-ylamine and Thiazolo [5, 4-b] pyridin-2-ylamine. Aniline/4-aminopyridine was converted to the corresponding thiourea derivatives, which were cyclized to obtain benzothiazol-2-ylamine/thiazolo [5, 4-b] pyridin-2-ylamine. Finally, these were condensed with various aromatic and heteroaromatic aldehydes to obtain Schiff bases of benzothiazol-2-ylamine and thiazolo [5, 4-b] pyridin-2-ylamine. The synthesized compounds were characterized and screened for their anticonvulsant activity using maximal electroshock (MES) test and isoniazid (INH) induced convulsions test. In-silico toxicity profiling of all the synthesized compounds was done through "Lazar" and "Osiris" properties explorer. Majority of the compounds were more potent against MES induced convulsions than INH induced convulsions. Schiff bases of benzothiazol-2-ylamine were more effective than thiazolo [5, 4-b] pyridin-2-ylamine against MES induced convulsions. The compound benzothiazol-2-yl-(1H-indol-2-ylmethylene)-amine (VI) was the most potent member of the series against both types of convulsions. Compound VI exhibited the most significant activity profile in both the models. The compounds did not exhibit any carcinogenicity or acute toxicity in the in-silico studies. Thus, it may be concluded that the Schiff bases of benzothiazol-2-ylamine exhibit the potential to be promising and non-toxic anticonvulsant agents.

  5. Electron attachment to indole and related molecules

    SciTech Connect

    Modelli, Alberto; Jones, Derek; Pshenichnyuk, Stanislav A.

    2013-11-14

    Gas-phase formation of temporary negative ion states via resonance attachment of low-energy (0–6 eV) electrons into vacant molecular orbitals of indoline (I), indene (II), indole (III), 2-methylen-1,3,3-trimethylindoline (IV), and 2,3,3-trimethyl-indolenine (V) was investigated for the first time by electron transmission spectroscopy (ETS). The description of their empty-level structures was supported by density functional theory and Hartree-Fock calculations, using empirically calibrated linear equations to scale the calculated virtual orbital energies. Dissociative electron attachment spectroscopy (DEAS) was used to measure the fragment anion yields generated through dissociative decay channels of the parent molecular anions of compounds I-V, detected with a mass filter as a function of the incident electron energy in the 0–14 eV energy range. The vertical and adiabatic electron affinities were evaluated at the B3LYP/6-31+G(d) level as the anion/neutral total energy difference. The same theoretical method is also used for evaluation of the thermodynamic energy thresholds for production of the negative fragments observed in the DEA spectra. The loss of a hydrogen atom from the parent molecular anion ([M-H]{sup −}) provides the most intense signal in compounds I-IV. The gas-phase DEAS data can provide support for biochemical reaction mechanisms in vivo involving initial hydrogen abstraction from the nitrogen atom of the indole moiety, present in a variety of biologically important molecules.

  6. Production of indole pigments by Candida glabrata.

    PubMed

    Mayser, Peter; Wenzel, Maja; Krämer, Hans-Joachim; Kindler, Bernhard L J; Spiteller, Peter; Haase, Gerhard

    2007-09-01

    When provided as the sole nitrogen source tryptophan induces the production of several indole alkaloids, e.g., pityriacitrin, malasseziaindole, pityriaanhydride and pityriarubin with proven biological activity in the lipophilic yeast Malassezia furfur. So far these pigments seem to have been unique and only produced by highly specialized basidiomycetal yeasts of the genus Malassezia. Having surprisingly observed a brown pigmented Candida glabrata isolate as a contaminant on such a pigment inducing culture plate, we systematically analyzed whether this ascomycetal yeast can also synthesize the respective pigments. Therefore, 30 Candida glabrata strains, including the ex-type strain CBS 138, were cultured for 2 weeks on a pigment-inducing medium containing L-tryptophan. This culture medium along with the resultant biomass was then extracted with ethyl acetate. The extracted pigments were separated into six fractions by column chromatography. Each of these fractions was subjected to thin-layer chromatography (TLC) on silica gel and yielded identical pigment bands comparable to those observed with M. furfur. In the case of strain CBS 138, the individual TLC zones were further purified by HPLC and structural analysis of the pure metabolites was performed by mass spectrometry and proton nuclear magnetic resonance ((1)H-NMR), thereby proving the presence of pityriacitrin, malassezia indole, pityriaanhydride and pityriarubin C. Since lineage divergence of Basidiomycota and Ascomycota occurred approximately 600 million years ago, our findings demonstrate that the complex underlying biochemical pathway has not been exclusively evolved in the highly adapted basidiomycetes yeast M. furfur, but instead seems to be rather fundamental and archaic. Therefore, further investigations on the potential biological properties and the genetic regulation of these metabolites are needed to elucidate their hitherto unknown functions.

  7. Cognition and order in Langmuir-Blodgett films of a 3-hexadecyl pyrrole and ferrocene-derivatized pyrrole mixed monolayer system

    NASA Astrophysics Data System (ADS)

    Samuelson, L.; Rahman, A. K. M.; Puglia, G. P.; Clough, S.; Tripathy, S.; Inagaki, T.; Yang, X. Q.; Skotheim, T. A.; Okamoto, Y.

    Novel, self-assembled materials were designed and produced from first principle to possess unique structural hierarchy and electronic and optical properties. The Langmuir-Blodgett technique was used to study the molecular organization of a mixed 3-hexadecyl pyrrole (3HDP) and ferrocene-derivatized pyrrole (Fc-Py) surfactant system. The pyrrole moiety was chosen for its' well established electronic and optical properties when polymerized, while ferrocene, it is theorized, if properly oriented into a Langmuir-Blodgett monolayer film may show a layered array of transition metals which would be extremely valuable as a model for 2-D magnets. The ferrocene group may also provide the possibility of charge coupling between neutral ferrocene and oxidized ferricenium which could be controlled electrochemically or photochemically. It has been determined that stable monolayer films of the mixed system could be formed at the air-water interface. The growth and assembly process led to polypyrrole 2-D lattices with heretofore unsurpassed order. In fact, the process of template polymerization leads to a new crystal phase for the polypyrrole component of the thin film structure. Various monolayer and multilayer films were prepared on platinum coated substrates for surface spectroscopic characterization using synchrotron radiation. Near Edge X-Ray Absorption Fine Structure studies revealed that highly ordered multilayer structures are being formed.

  8. Cognition and order in Langmuir-Blodgett films of a 3-hexadecyl pyrrole and ferrocene-derivatized pyrrole mixed monolayer system

    SciTech Connect

    Samuelson, L.; Rahman, A.K.M.; Puglia, G.P.; Clough, S.; Tripathy, S.; Inagaki, T.; Yang, X.Q.; Skotheim, T.A.; Okamoto, Y.

    1989-01-01

    Novel, self-assembled materials have been designed and produced from first principle to possess unique structural hierarchy and electronic and optical properties. The Langmuir-Blodgett technique was used to study the molecular organization of a mixed 3-hexadecyl pyrrole (3HDP) and ferrocene-derivatized pyrrole (Fc-Py) surfactant system. The pyrrole moiety was chosen for its' well established electronic and optical properties when polymerized, while ferrocene, it is theorized, if properly oriented into a Langmuir-Blodgett monolayer film may show a layered array of transition metals which would be extremely valuable as a model for two-dimensional magnets. The ferrocene group may also provide the possibility of charge coupling between neutral ferrocene and oxidized ferricenium which could be controlled electrochemically or photochemically. It has been determined that stable monolayer films of the mixed system could be formed at the air-water interface. The growth and assembly process led to polypyrrole 2-D lattices with heretofore unsurpassed order. In fact, the process of template polymerization leads to a new crystal phase for the polypyrrole component of the thin film structure. Various monolayer and multilayer films were prepared on platinum coated substrates for surface spectroscopic characterization using synchrotron radiation. Near Edge X-Ray Absorption Fine Structure studies revealed that highly ordered multilayer structures are being formed. 8 refs., 4 figs., 1 tab.

  9. Gold Catalysed Redox Synthesis of Imidazo[1,2-a]pyridine using Pyridine N-Oxide and Alkynes

    PubMed Central

    Talbot, Eric P. A.; Richardson, Melodie; McKenna, Jeffrey M.; Toste, F. Dean

    2014-01-01

    A mild, catalytic, atom economical synthesis of imidazo[1,2-a]pyridines has been developed: catalytic PicAuCl2 in the presence of an acid produces a range imidazo[1,2-a]pyridines in good yield. This strategy is mild and forseen to be of particular use for the installation of stereogenic centers adjacent to the imidazo[1,2-a]pyridine ring without loss of enantiomeric excess. PMID:24839436

  10. Enantiopure oxazolidinones as chiral acids in the asymmetric protonation of N-Boc pyrrole derived enolates.

    PubMed

    Carbery, David R; Donohoe, Timothy J

    2004-03-21

    The first use of geminally disubstituted oxazolidinones as chiral protonating agents is described: these new acids are able to directly protonate an enolate generated by the ammonia free partial reduction of an electron deficient pyrrole and give up to 68% ee in the pyrroline product.

  11. Synthesis and Evaluation of Novel Pyrroles and Pyrrolopyrimidines as Anti-Hyperglycemic Agents

    PubMed Central

    Mohamed, M. S.; Ali, S. A.; Abdelaziz, D. H. A.; Fathallah, Samar S.

    2014-01-01

    A series of pyrrole and pyrrolopyrimidine derivatives were examined for their in vivo antihyperglycemic activity. Compounds Ia–c,e, and IVg showed promising antihyperglycemic activity equivalent to a well-known standard antihyperglycemic drug, Glimepiride (Amaryl, 4 mg/kg). In this paper, we examine and discuss the structure-activity relationships and antihyperglycemic activity of these compounds. PMID:25054134

  12. Identification of a new electron-transfer relaxation pathway in photoexcited pyrrole dimers

    NASA Astrophysics Data System (ADS)

    Neville, Simon P.; Kirkby, Oliver M.; Kaltsoyannis, Nikolas; Worth, Graham A.; Fielding, Helen H.

    2016-04-01

    Photoinduced electron transfer is central to many biological processes and technological applications, such as the harvesting of solar energy and molecular electronics. The electron donor and acceptor units involved in electron transfer are often held in place by covalent bonds, π-π interactions or hydrogen bonds. Here, using time-resolved photoelectron spectroscopy and ab initio calculations, we reveal the existence of a new, low-energy, photoinduced electron-transfer mechanism in molecules held together by an NH⋯π bond. Specifically, we capture the electron-transfer process in a pyrrole dimer, from the excited π-system of the donor pyrrole to a Rydberg orbital localized on the N-atom of the acceptor pyrrole, mediated by an N-H stretch on the acceptor molecule. The resulting charge-transfer state is surprisingly long lived and leads to efficient electronic relaxation. We propose that this relaxation pathway plays an important role in biological and technological systems containing the pyrrole building block.

  13. Calix[4]pyrrole: A New Ion-Pair Receptor As Demonstrated by Liquid-Liquid Extraction

    SciTech Connect

    Wintergerst, Mr. Matthieu; Levitskaia, Tatiana G.; Moyer, Bruce A; Sessler, Jonathan L.; Delmau, Laetitia Helene

    2008-01-01

    Solvent-extraction studies provide confirming evidence that meso-octamethylcalix[4]pyrrole acts as an ion-pair receptor for cesium chloride and cesium bromide in nitrobenzene solution. The stoichiometry of the interaction under extraction conditions from water to nitrobenzene was determined from plots of the cesium distribution ratios vs cesium salt and receptor concentration, indicating the formation of an ionpaired 1:1:1 cesium:calix[4]pyrrole:halide complex. The extraction results were modeled to evaluate the equilibria inherent to the solvent-extraction system, with either chloride or bromide. The binding energy between the halide anion and the calix[4]pyrrole was found to be about 7 kJ/mol larger for cesium chloride than for the cesium bromide. The ion-pairing free energies between the calix[4]pyrrole-halide complex and the cesium cation are nearly the same within experimental uncertainty for either halide, consistent with a structural model in which the Cs+ cation resides in the calix bowl. These results are unexpected since nitrobenzene is a polar solvent that generally leads to dissociated complexes in the organic phase when used as a diluent in extraction studies of univalent ions. Control studies involving nitrate revealed no evidence of ion pairing for CsNO3 under conditions identical to those where it is observed for CsCl and CsBr.

  14. Calix[4]pyrrole: A New Ion-Pair Receptor As Demonstrated by Liquid-Liquid Extraction

    SciTech Connect

    Wintergerst, Mr. Matthieu; Levitskaia, Tatiana G.; Moyer, Bruce A; Sessler, Jonathan L.; Delmau, Laetitia Helene

    2008-01-01

    Solvent extraction studies provide confirming evidence that meso-octamethylcalix[4]pyrrole acts as an ion-pair receptor for cesium chloride and cesium bromide in nitrobenzene solution. The stoichiometry of the interaction under extraction conditions from water to nitrobenzene was determined from plots of the cesium distribution ratios vs. cesium salt and receptor concentration, indicating the formation of an ion-paired 1:1:1 cesium:calix[4]pyrrole:halide complex. The extraction results were modeled to evaluate the equilibria inherent to the solvent extraction system, either with chloride or bromide. The binding energy between the halide anion and the calix[4]pyrrole was found to be about 7 kJ/mol larger for cesium chloride than for the cesium bromide. The ion-pairing free energies between the calix[4]pyrrole-halide complex and the cesium cation are nearly the same within experimental uncertainty for either halide, consistent with a structural model in which the Cs+ cation resides in the calix bowl. These results are unexpected since nitrobenzene is a very polar solvent that generally leads to dissociated complexes in the organic phase when used as a diluent in extraction studies of univalent ions. Control studies involving nitrate revealed no evidence of ion-pairing for CsNO3 under conditions identical to those where it is observed for CsCl and CsBr.

  15. Intramolecular redox reaction for the synthesis of N-aryl pyrroles catalyzed by Lewis acids.

    PubMed

    Du, Hong-Jin; Zhen, Le; Wen, Xiaoan; Xu, Qing-Long; Sun, Hongbin

    2014-12-21

    An efficient approach to synthesize N-aryl pyrroles via Lewis acid-mediated 1,5-hydride shift and isomerization of 2-(3-pyrroline-1-yl)arylaldehydes has been achieved in up to 89% yield. This methodology is applicable to the synthesis of fluorazene derivatives as electron donor (D)/acceptor (A) molecules.

  16. Translocation of radiolabeled indole-3-acetic acid and indole-3-acetyl-myo-inositol from kernel to shoot of Zea mays L

    NASA Technical Reports Server (NTRS)

    Chisnell, J. R.; Bandurski, R. S.

    1988-01-01

    Either 5-[3H]indole-3-acetic acid (IAA) or 5-[3H]indole-3-acetyl-myo-inositol was applied to the endosperm of kernels of dark-grown Zea mays seedlings. The distribution of total radioactivity, radiolabeled indole-3-acetic acid, and radiolabeled ester conjugated indole-3-acetic acid, in the shoots was then determined. Differences were found in the distribution and chemical form of the radiolabeled indole-3-acetic acid in the shoot depending upon whether 5-[3H]indole-3-acetic acid or 5-[3H]indole-3-acetyl-myo-inositol was applied to the endosperm. We demonstrated that indole-3-acetyl-myo-inositol applied to the endosperm provides both free and ester conjugated indole-3-acetic acid to the mesocotyl and coleoptile. Free indole-3-acetic acid applied to the endosperm supplies some of the indole-3-acetic acid in the mesocotyl but essentially no indole-3-acetic acid to the coleoptile or primary leaves. It is concluded that free IAA from the endosperm is not a source of IAA for the coleoptile. Neither radioactive indole-3-acetyl-myo-inositol nor IAA accumulates in the tip of the coleoptile or the mesocotyl node and thus these studies do not explain how the coleoptile tip controls the amount of IAA in the shoot.

  17. Translocation of radiolabeled indole-3-acetic acid and indole-3-acetyl-myo-inositol from kernel to shoot of Zea mays L

    NASA Technical Reports Server (NTRS)

    Chisnell, J. R.; Bandurski, R. S.

    1988-01-01

    Either 5-[3H]indole-3-acetic acid (IAA) or 5-[3H]indole-3-acetyl-myo-inositol was applied to the endosperm of kernels of dark-grown Zea mays seedlings. The distribution of total radioactivity, radiolabeled indole-3-acetic acid, and radiolabeled ester conjugated indole-3-acetic acid, in the shoots was then determined. Differences were found in the distribution and chemical form of the radiolabeled indole-3-acetic acid in the shoot depending upon whether 5-[3H]indole-3-acetic acid or 5-[3H]indole-3-acetyl-myo-inositol was applied to the endosperm. We demonstrated that indole-3-acetyl-myo-inositol applied to the endosperm provides both free and ester conjugated indole-3-acetic acid to the mesocotyl and coleoptile. Free indole-3-acetic acid applied to the endosperm supplies some of the indole-3-acetic acid in the mesocotyl but essentially no indole-3-acetic acid to the coleoptile or primary leaves. It is concluded that free IAA from the endosperm is not a source of IAA for the coleoptile. Neither radioactive indole-3-acetyl-myo-inositol nor IAA accumulates in the tip of the coleoptile or the mesocotyl node and thus these studies do not explain how the coleoptile tip controls the amount of IAA in the shoot.

  18. Oxidative Furan-to-Indole Rearrangement. Synthesis of 2-(2-Acylvinyl)indoles and Flinderole C Analogues.

    PubMed

    Makarov, Anton S; Merkushev, Anton A; Uchuskin, Maxim G; Trushkov, Igor V

    2016-05-06

    Oxidative rearrangement of 2-(2-aminobenzyl)furans affording 2-(2-acylvinyl)indoles in a stereocontrolled manner in good-to-excellent yields has been developed. Thus, (2-aminobenzyl)furans with electron-releasing alkoxy substituents in the phenyl group form only E-isomers of 2-(2-acylvinyl)indoles. Conversely, substrates without such substituents produce target products as Z-isomers exclusively. A short diastereoselective method for the transformation of the obtained 2-(2-acylvinyl)indoles into antimalarial bisindole alkaloid flinderole A-C analogues has been developed.

  19. Effective adsorptive removal of indole from model fuel using a metal-organic framework functionalized with amino groups.

    PubMed

    Ahmed, Imteaz; Jhung, Sung Hwa

    2015-01-01

    Nitrogen-containing compounds (NCCs) should be removed from fuels because of the negative effect of NCCs on the environment and catalyst stability. NCCs are composed of basic materials such as quinoline (QUI) and neutral materials such as indole (IND). The NCCs can be removed by various methods including adsorption. Compared with basic NCCs, neutral NCCs are more difficult to remove through adsorption due to their less affinity toward adsorbents. In this report, adsorption of IND (as one of the representative neutral NCCs) was studied over the metal-organic frameworks (MOFs), UiO-66 and UiO-66-NH2, which contain terephthalate and aminoterephthalate linkers, respectively. In spite of the reduced porosity of UiO-66-NH2, the adsorption capacity of IND was improved upto 46% when compared with pristine UiO-66. Therefore, the additional amino group in the MOF imparts extra adsorption capability on the MOF. For a detailed investigation, adsorption of other NCCs such as QUI, pyrrole, and methylpyrrole was studied. The improved adsorption of IND over amino-functionalized MOFs could be attributed to the improved interaction of IND with the MOF via H-bonding because of the NH2 group. In addition to this remarkable improvement in IND adsorption, UiO-66-NH2 could be regenerated several times for the adsorption of IND by simple solvent washing.

  20. Indole-3-Acetic Acid Biosynthesis in Colletotrichum gloeosporioides f. sp. aeschynomene

    PubMed Central

    Robinson, M.; Riov, J.; Sharon, A.

    1998-01-01

    We characterized the biosynthesis of indole-3-acetic acid by the mycoherbicide Colletotrichum gloeosporioides f. sp. aeschynomene. Auxin production was tryptophan dependent. Compounds from the indole-3-acetamide and indole-3-pyruvic acid pathways were detected in culture filtrates. Feeding experiments and in vitro assay confirmed the presence of both pathways. Indole-3-acetamide was the major pathway utilized by the fungus to produce indole-3-acetic acid in culture. PMID:9835603

  1. Aza-tryptamine substrates in monoterpene indole alkaloid biosynthesis

    PubMed Central

    Lee, Hyang-Yeol; Yerkes, Nancy; O’Connor, Sarah E.

    2009-01-01

    Biosynthetic pathways can be hijacked to yield novel compounds by introduction of novel starting materials. Here we have altered tryptamine, which serves as the starting substrate for a variety of alkaloid biosynthetic pathways, by replacing the indole with one of four aza-indole isomers. We show that two aza-tryptamine substrates can be successfully incorporated into the products of the monoterpene indole alkaloid pathway in Catharanthus roseus. Use of unnatural heterocycles in precursor directed biosynthesis, in both microbial and plant natural product pathways, has not been widely demonstrated, and successful incorporation of starting substrate analogs containing the aza-indole functionality has not been previously reported. This work serves as a starting point to explore fermentation of aza-alkaloids from other tryptophan and tryptamine derived natural product pathways. PMID:20064432

  2. Aza-tryptamine substrates in monoterpene indole alkaloid biosynthesis.

    PubMed

    Lee, Hyang-Yeol; Yerkes, Nancy; O'Connor, Sarah E

    2009-12-24

    Biosynthetic pathways can be hijacked to yield novel compounds by introduction of novel starting materials. Here we have altered tryptamine, which serves as the starting substrate for a variety of alkaloid biosynthetic pathways, by replacing the indole with one of four aza-indole isomers. We show that two aza-tryptamine substrates can be successfully incorporated into the products of the monoterpene indole alkaloid pathway in Catharanthus roseus. Use of unnatural heterocycles in precursor-directed biosynthesis, in both microbial and plant natural product pathways, has not been widely demonstrated, and successful incorporation of starting substrate analogs containing the aza-indole functionality has not been previously reported. This work serves as a starting point to explore fermentation of aza-alkaloids from other tryptophan- and tryptamine-derived natural product pathways.

  3. Epidemiology, pathology and treatment of non-follicular indolent lymphomas.

    PubMed

    Landgren, Ola; Tilly, Hervé

    2008-01-01

    Non-follicular indolent subtypes of non-Hodgkin lymphoma (NHL), which include chronic lymphocytic leukemia, small lymphocytic lymphoma (SLL) and marginal zone lymphomas (MZL), are a diverse group of disorders with different presenting features, behaviour patterns and treatment outcomes. Current knowledge of these subtypes is largely based on retrospective analyses. A precise diagnosis can be difficult to achieve, and specific diagnostic criteria are needed to more precisely define some of the rarer indolent tumors, such as nodal and splenic MZLs. Although some subtypes of NHL have a prolonged indolent course, with a good prognosis (e.g. SLL), others (e.g. nodal and splenic MZLs) can rapidly evolve into more aggressive subtypes. In asymptomatic patients, treatment may be deferred until the disease progresses and the patient becomes symptomatic. Universally accepted therapeutic guidelines do not exist, however, and carefully designed, prospective clinical studies are needed to further assess optimal therapeutic approaches for these indolent NHLs.

  4. Ab initio quantum chemical and kinetic modeling study of the pyrolysis kinetics of pyrrole

    SciTech Connect

    Martoprawiro, M.; Bacskay, G.B.; Mackie, J.C.

    1999-05-20

    The five-membered heterocyclic pyrrole moiety is an important structure in coals and derived tars, and the thermal decomposition reactions of pyrrole are important for production of precursors of the oxides of nitrogen, NO{sub x}, in the combustion of coals. The kinetics of pyrolysis of pyrrole have been investigated theoretically by ab initio quantum chemical techniques and by detailed chemical kinetic modeling of previously reported experimental results. The overall kinetics can be successfully modeled by a 117 step kinetic model that gives good agreement with temperature profiles of major products and also provides an acceptable fit for minor products. The thermochemistry and rate parameters of a number of key reactions have been obtained by ab initio calculations carried out at CASSCF, CASPT2, and G2(MP2) levels of theory. Several reaction pathways were investigated. The major product, HCN, arises principally from a hydrogen migration in pyrrole to form a cyclic carbene with the NH bond intact. Ring scission of this carbene leads to an allenic imine precursor of HCN and propyne. This is the decomposition pathway of lowest energy. Pyrolysis is preceded by the facile tautomerization of pyrrole to 2H-pyrrolenine. The latter can undergo CN fission to form an open chain biradical species, which is the precursor of the butenenitrile isomeric products, cis- and trans-crotononitrile and allyl cyanide. The biradical can also undergo facile H-fission to form cyanoallyl radical, which is an important precursor of acetylene, acetonitrile, and acrylonitrile, H{sub 2} also arises principally from H-fission of the biradical.

  5. Design and synthesis of hybrid cyclophanes containing thiophene and indole units via Grignard reaction, Fischer indolization and ring-closing metathesis as key steps

    PubMed Central

    2015-01-01

    Summary We demonstrate a new synthetic strategy to cyclophanes containing thiophene and indole moieties via Grignard addition, Fischer indolization and ring-closing metathesis as key steps. PMID:26425209

  6. The copper-catalyzed N-arylation of indoles.

    PubMed

    Antilla, Jon C; Klapars, Artis; Buchwald, Stephen L

    2002-10-02

    A general method for the N-arylation of indoles using catalysts derived from CuI and trans-1,2-cyclohexanediamine (1a), trans-N,N'-dimethyl-1,2-cyclohexanediamine (2a), or N,N'-dimethyl-ethylenediamine (3) is reported. N-Arylindoles can be produced in high yield from the coupling of an aryl iodide or aryl bromide with a variety of indoles.

  7. Dissociative Ionization of Pyridine by Electron Impact

    NASA Technical Reports Server (NTRS)

    Dateo, Christopher; Huo, Winifred; Kwak, Dochan (Technical Monitor)

    2002-01-01

    In order to understand the damage of biomolecules by electrons, a process important in radiation damage, we undertake a study of the dissociative ionization (DI) of pyridine (C5H5N) from the low-lying ionization channels. The methodology used is the same as in the benzene study. While no experimental DI data are available, we compare the dissociation products from our calculations with the dissociative photoionization measurements of Tixier et al. using dipole (e, e(+) ion) coincidence spectroscopy. Comparisons with the DI of benzene is also made so as to understand the difference in DI between a heterocyclic and an aromatic molecule.

  8. [Biodegradation of pyridine by Shinella zoogloeoides BC026].

    PubMed

    Sun, Qing-Hua; Bai, Yao-Hui; Zhao, Cui; Wen, Dong-Hui; Tang, Xiao-Yan

    2008-10-01

    A bacterial strain BC026 capable of utilizing pyridine as its sole source of carbon and nitrogen was isolated from the activated sludge in a coking wastewater treatment plant. The bacterium featured flocculability and antibiotic resistance to kanamycin, ampicillin and spectinomycine. It could grow well in Ashby nitrogen free culture medium. The strain was identified as Shinella zoogloeoides according to the results of 16S rRNA sequence analysis and Biolog microbial identification system. The experiments of pyridine biodegradation by the pure culture showed that pyridine of 400 mg/L could be degraded completely in 17 h under the condition of inoculum 0.1 g/L, 30 degrees C, 180 r/min and pH 7. BC026 could keep high degradative activity in mineral salt medium containing pyridine with a concentration ranging from 99 mg/L to 1 806 mg/L. Higher initial concentration of pyridine caused repression on BC026 to a certain extent, however, the degradation rate became faster after the strain had been accommodated. The optimal conditions for the degradation were 30-35 degrees C and pH 8. The research on metabolic pathway of pyridine by BC026 indicated that the first step of pyridine degradation was C-N bonds cleavage, generating NH4+ and glutaraldehyde. Then glutaraldehyde was oxidized into glutaric acid, and finally into CO2 and H2O. 59.5% nitrogen from pyridine was transferred into ammonium in the whole degradation.

  9. Pyridine is an organocatalyst for the reductive ozonolysis of alkenes

    PubMed Central

    Willand-Charnley, Rachel; Fisher, Thomas J.; Johnson, Bradley M.; Dussault, Patrick H.

    2012-01-01

    Whereas the cleavage of alkenes by ozone typically generates peroxide intermediates that must be decomposed in an accompanying step, ozonolysis in the presence of pyridine directly generates ketones or aldehydes through a process that neither consumes pyridine nor generates any detectable peroxides. The reaction is hypothesized to involve nucleophile-promoted fragmentation of carbonyl oxides via formation of zwitterionic peroxyacetals. PMID:22512349

  10. Degradation of pyridine by Micrococcus luteus isolated from soil

    SciTech Connect

    Sims, G.K.; Sommers, L.E.; Konopka, A.

    1986-05-01

    An organism capable of growth on pyridine was isolated from soil by enrichment culture techniques and identified as Micrococcus luteus. The organism oxidized pyridine for energy and released N contained in the pyridine ring as ammonium. The organism could not grow on mono- or disubstituted pyridinecarboxylic acids or hydroxy-, chloro-, amino-, or methylpyridines. Cell extracts of M. luteus could not degrade pyridine, 2-, 3-, or 4-hydroxypyridines or 2,3-dihydroxypyridine, regardless of added cofactors or cell particulate fraction. The organism had a NAD-linked succinate-semialdehyde dehydrogenase which was induced by pyridine. Cell extracts of M. luteus had constitutive amidase activity, and washed cells degraded formate and formamide without a lag. These data are consistent with a previously reported pathway for pyridine metabolism by species of Bacillus, Brevibacterium, and Corynebacterium. Cells of M. luteus were permeable to pyridinecarboxylic acids, monohydroxypyridines, 2,3-dihydroxypyridine, and monoamino- and methylpyridines. The results provide new evidence that the metabolism of pyridine by microorganisms does not require initial hydroxylation of the ring and that permeability barriers do not account for the extremely limited range of substrate isomers used by pyridine degraders.

  11. Degradation of Pyridine by Micrococcus luteus Isolated from Soil †

    PubMed Central

    Sims, Gerald K.; Sommers, Lee E.; Konopka, Allan

    1986-01-01

    An organism capable of growth on pyridine was isolated from soil by enrichment culture techniques and identified as Micrococcus luteus. The organism oxidized pyridine for energy and released N contained in the pyridine ring as ammonium. The organism could not grow on mono- or disubstituted pyridinecarboxylic acids or hydroxy-, chloro-, amino-, or methylpyridines. Cell extracts of M. luteus could not degrade pyridine, 2-, 3-, or 4-hydroxypyridines or 2,3-dihydroxypyridine, regardless of added cofactors or cell particulate fraction. The organism had a NAD-linked succinate-semialdehyde dehydrogenase which was induced by pyridine. Cell extracts of M. luteus had constitutive amidase activity, and washed cells degraded formate and formamide without a lag. These data are consistent with a previously reported pathway for pyridine metabolism by species of Bacillus, Brevibacterium, and Corynebacterium. Cells of M. luteus were permeable to pyridinecarboxylic acids, monohydroxypyridines, 2,3-dihydroxypyridine, and monoamino- and methylpyridines. The results provide new evidence that the metabolism of pyridine by microorganisms does not require initial hydroxylation of the ring and that permeability barriers do not account for the extremely limited range of substrate isomers used by pyridine degraders. PMID:16347070

  12. Indole and 7‐hydroxyindole diminish Pseudomonas aeruginosa virulence

    PubMed Central

    Lee, Jintae; Attila, Can; Cirillo, Suat L. G.; Cirillo, Jeffrey D.; Wood, Thomas K.

    2009-01-01

    Summary Indole is an extracellular biofilm signal for Escherichia coli, and many bacterial oxygenases readily convert indole to various oxidized compounds including 7‐hydroxyindole (7HI). Here we investigate the impact of indole and 7HI on Pseudomonas aeruginosa PAO1 virulence and quorum sensing (QS)‐regulated phenotypes; this strain does not synthesize these compounds but degrades them rapidly. Indole and 7HI both altered extensively gene expression in a manner opposite that of acylhomoserine lactones; the most repressed genes encode the mexGHI‐opmD multidrug efflux pump and genes involved in the synthesis of QS‐regulated virulence factors including pyocyanin (phz operon), 2‐heptyl‐3‐hydroxy‐4(1H)‐quinolone (PQS) signal (pqs operon), pyochelin (pch operon) and pyoverdine (pvd operon). Corroborating these microarray results, indole and 7HI decreased production of pyocyanin, rhamnolipid, PQS and pyoverdine and enhanced antibiotic resistance. In addition, indole affected the utilization of carbon, nitrogen and phosphorus, and 7HI abolished swarming motility. Furthermore, 7HI reduced pulmonary colonization of P. aeruginosa in guinea pigs and increased clearance in lungs. Hence, indole‐related compounds have potential as a novel antivirulence approach for the recalcitrant pathogen P. aeruginosa. PMID:21261883

  13. Photoreaction of indole-containing mycotoxins to fluorescent products.

    PubMed

    Maragos, C M

    2009-06-01

    Photochemical reaction of the non-fluorescent mycotoxin cyclopiazonic acid (CPA) to fluorescent products was recently reported. Because CPA contains an indole moiety, believed to contribute to the fluorescence, it was of interest to determine whether the effect might be more generally applicable to indole-containing mycotoxins. Three indole-containing tremorgens (penitrem A, paxilline, verruculogen) that have not previously been reported to be fluorescent were rendered fluorescent by exposure to ultraviolet light in a photoreactor. Naturally fluorescent ergot alkaloids, which also contain an indole-moiety, exhibited a diminished response after exposure. This suggests that the phenomenon may be most useful for detection of indole-containing tremorgens that are non-fluorescent, rather than for the enhancement of materials that are already fluorescent, such as the ergot alkaloids. The extent to which fluorescence enhancement was seen was strongly influenced by the reaction environment, in particular the solvent used and whether cyclodextrins were present. In an HPLC format, placement of the photoreactor post-column allowed for the fluorescence detection of penitrem A, paxilline, and verruculogen. The ability to photoreact indole-containing tremorgens and detect them by fluorescence may open up new avenues for detection of these mycotoxins alone or in combination.

  14. Indole: An evolutionarily conserved influencer of behavior across kingdoms.

    PubMed

    Tomberlin, Jeffery K; Crippen, Tawni L; Wu, Guoyao; Griffin, Ashleigh S; Wood, Thomas K; Kilner, Rebecca M

    2017-02-01

    Indole is a key environmental cue that is used by many organisms. Based on its biochemistry, we suggest indole is used so universally, and by such different organisms, because it derives from the metabolism of tryptophan, a resource essential for many species yet rare in nature. These properties make it a valuable, environmental cue for resources almost universally important for promoting fitness. We then describe how indole is used to coordinate actions within organisms, to influence the behavior of conspecifics and can even be used to change the behavior of species that belong to other kingdoms. Drawing on the evolutionary framework that has been developed for understanding animal communication, we show how this is diversely achieved by indole acting as a cue, a manipulative signal, and an honest signal, as well as how indole can be used synergistically to amplify information conveyed by other molecules. Clarifying these distinct functions of indole identifies patterns that transcend different kingdoms of organisms. © 2016 WILEY Periodicals, Inc.

  15. Synthesis and biological evaluation of new 3-(6-hydroxyindol-2-yl)-5-(Phenyl) pyridine or pyrazine V-Shaped molecules as kinase inhibitors and cytotoxic agents.

    PubMed

    Kassis, Pamela; Brzeszcz, Joanna; Bénéteau, Valérie; Lozach, Olivier; Meijer, Laurent; Le Guével, Rémi; Guillouzo, Christiane; Lewiński, Krzysztof; Bourg, Stéphane; Colliandre, Lionel; Routier, Sylvain; Mérour, Jean-Yves

    2011-11-01

    We here report the synthesis and biological evaluation of new 3-[(2-indolyl)]-5-phenyl-3,5-pyridine, 3-[(2-indolyl)]-5-phenyl-2,4-pyridine and 3-[(2-indolyl)]-5-phenyl-2,6-pyrazine derivatives designed as potential CDK inhibitors. Indoles and phenyls were used to generate several substitutions of the pyridine and pyrazine rings. The synthesis included Stille or Suzuki type reactions, which were carried out on the 3,5-dibromopyridine, 2,4-dichloropyridine and 2,6-dichloro-1-4-pyrazine moieties. Cell effects of the V-shaped family were in the micromolar range. Kinase assays were conducted and showed that compound 11 inhibited CDK5 with an inhibitory concentration of 160 nM with a moderate selectivity over GSK3 compared to the reference C which exhibited a slightly lower activity on CDK5 (1.5 μM). Compound 11 was also found to be the most potent compound in the series and was identified as a new lead for DYRK1A inhibitor discovery (IC(50) = 60 nM). Docking studies were carried out in order to investigate the inhibition of DYRK1A.

  16. Friedel-Crafts Fluoroacetylation of Indoles with Fluorinated Acetic Acids for the Synthesis of Fluoromethyl Indol-3-yl Ketones under Catalyst- and Additive-Free Conditions.

    PubMed

    Yao, Shun-Jiang; Ren, Zhi-Hui; Wang, Yao-Yu; Guan, Zheng-Hui

    2016-05-20

    A simple and efficient protocol for the fluoroacetylation of indoles is reported. The reaction uses fluorinated acetic acids as the fluoroacetylation reagents to synthesize diverse fluoromethyl indol-3-yl ketones in good yields under catalyst- and additive-free conditions. In addition, the only byproduct is water in this transformation. The synthetic utility of this reaction was also demonstrated by the concise synthesis of α-(trifluoromethyl)(indol-3-yl)methanol and indole-3-carboxylic acid.

  17. 2-Phenyl-2-(pyridin-2-yl)hexahydro­pyrimidine

    PubMed Central

    Jayaratna, Naleen B.; Norman, Richard E.

    2010-01-01

    The title compound, C15H17N3, was prepared by reaction of benzoyl­pyridine and hexahydropyrimidine. The 1,3-diazinane ring adopts a chair conformation with one N—H group axial and the other equatorial. The axial N—H group participates in very weak hydrogen bonding to the lone pair of electrons of the N atom with the equatorial H atom producing a very weakly hydrogen-bonded dimer. The pyridine N atom accepts an inter­nal hydrogen bond from the equatorial H atom. The phenyl ring adopts an equatorial position while the pyridine ring is axial. The phenyl ring exhibits a slight twist (ca 25°) relative to the hexahydropyrimidine ring. The pyridine ring stacks with symmetry-related pyridine rings. PMID:21589448

  18. UV-photoelectron spectroscopy of BN indoles: experimental and computational electronic structure analysis.

    PubMed

    Chrostowska, Anna; Xu, Senmiao; Mazière, Audrey; Boknevitz, Katherine; Li, Bo; Abbey, Eric R; Dargelos, Alain; Graciaa, Alain; Liu, Shih-Yuan

    2014-08-20

    We present a comprehensive electronic structure analysis of two BN isosteres of indole using a combined UV-photoelectron spectroscopy (UV-PES)/computational chemistry approach. Gas-phase He I photoelectron spectra of external BN indole I and fused BN indole II have been recorded, assessed by density functional theory calculations, and compared with natural indole. The first ionization energies of these indoles are natural indole (7.9 eV), external BN indole I (7.9 eV), and fused BN indole II (8.05 eV). The computationally determined molecular dipole moments are in the order: natural indole (2.177 D) > fused BN indole II (1.512 D) > external BN indole I (0.543 D). The λmax in the UV-vis absorption spectra are in the order: fused BN indole II (292 nm) > external BN indole I (282 nm) > natural indole (270 nm). The observed relative electrophilic aromatic substitution reactivity of the investigated indoles with dimethyliminium chloride as the electrophile is as follows: fused BN indole II > natural indole > external BN indole I, and this trend correlates with the π-orbital coefficient at the 3-position. Nucleus-independent chemical shifts calculations show that the introduction of boron into an aromatic 6π-electron system leads to a reduction in aromaticity, presumably due to a stronger bond localization. Trends and conclusions from BN isosteres of simple monocyclic aromatic systems such as benzene and toluene are not necessarily translated to the bicyclic indole core. Thus, electronic structure consequences resulting from BN/CC isosterism will need to be evaluated individually from system to system.

  19. Partial purification and characterization of indol-3-ylacetylglucose:myo-inositol indol-3-ylacetyltransferase (indoleacetic acid-inositol synthase)

    NASA Technical Reports Server (NTRS)

    Kesy, J. M.; Bandurski, R. S.

    1990-01-01

    A procedure is described for the purification of the enzyme indol-3-ylacetylglucose:myo-inositol indol-3-ylacetyltransferase (IAA-myo-inositol synthase). This enzyme catalyzes the transfer of indol-3-ylacetate from 1-0-indol-3-ylacetyl-beta-d-glucose to myo-inositol to form indol-3-ylacetyl-myo-inositol and glucose. A hexokinase or glucose oxidase based assay system is described. The enzyme has been purified approximately 16,000-fold, has an isoelectric point of pH 6.1 and yields three catalytically inactive bands upon acrylamide gel electrophoresis of the native protein. The enzyme shows maximum transferase activity with myo-inositol but shows some transferase activity with scyllo-inositol and myo-inosose-2. No transfer of IAA occurs with myo-inositol-d-galactopyranose, cyclohexanol, mannitol, or glycerol as acyl acceptor. The affinity of the enzyme for 1-0-indol-3-ylacetyl-beta-d-glucose is, Km = 30 micromolar, and for myo-inositol is, Km = 4 millimolar. The enzyme does not catalyze the exchange incorporation of glucose into IAA-glucose indicating the reaction mechanism involves binding of IAA glucose to the enzyme with subsequent hydrolytic cleavage of the acyl moiety by the hydroxyl of myo-inositol to form IAA myo-inositol ester.

  20. Partial purification and characterization of indol-3-ylacetylglucose:myo-inositol indol-3-ylacetyltransferase (indoleacetic acid-inositol synthase)

    NASA Technical Reports Server (NTRS)

    Kesy, J. M.; Bandurski, R. S.

    1990-01-01

    A procedure is described for the purification of the enzyme indol-3-ylacetylglucose:myo-inositol indol-3-ylacetyltransferase (IAA-myo-inositol synthase). This enzyme catalyzes the transfer of indol-3-ylacetate from 1-0-indol-3-ylacetyl-beta-d-glucose to myo-inositol to form indol-3-ylacetyl-myo-inositol and glucose. A hexokinase or glucose oxidase based assay system is described. The enzyme has been purified approximately 16,000-fold, has an isoelectric point of pH 6.1 and yields three catalytically inactive bands upon acrylamide gel electrophoresis of the native protein. The enzyme shows maximum transferase activity with myo-inositol but shows some transferase activity with scyllo-inositol and myo-inosose-2. No transfer of IAA occurs with myo-inositol-d-galactopyranose, cyclohexanol, mannitol, or glycerol as acyl acceptor. The affinity of the enzyme for 1-0-indol-3-ylacetyl-beta-d-glucose is, Km = 30 micromolar, and for myo-inositol is, Km = 4 millimolar. The enzyme does not catalyze the exchange incorporation of glucose into IAA-glucose indicating the reaction mechanism involves binding of IAA glucose to the enzyme with subsequent hydrolytic cleavage of the acyl moiety by the hydroxyl of myo-inositol to form IAA myo-inositol ester.

  1. Van der Waals Interactions in Pyridine and Pyridine-like Molecular Crystals: An ab initio Molecular Dynamics Study

    NASA Astrophysics Data System (ADS)

    Ko, Hsin-Yu; Distasio, Robert A., Jr.; Santra, Biswajit; Car, Roberto

    2014-03-01

    Pyridine has recently been investigated as a potentially effective material for use in artificial light harvesting.In this work, we propose the use of ab initio molecular dynamics (AIMD) to gain valuable physical insight into the artificial photosynthetic processes occurring in condensed-phase pyridine, the study of which has been limited to semi-empirical force fields to date.For this purpose, we introduce an accurate and efficient AIMD method, based on density functional theory (DFT) and a self-consistent pairwise description of van der Waals (vdW) interactions, for use in finite temperature and pressure (NPT) simulations on pyridine and several pyridine-like molecular crystals (PLMCs). Utilizing this approach, we demonstrate that vdW forces play a crucial role in the theoretical prediction of the structure and density of pyridine and PLMCs, and therefore must be accounted for in studies of these potential alternative energy materials. DOE: DE-SC0008626, NSF: DMS-1065894.

  2. Synthesis of chiral macrocyclic or linear pyridine carboxamides from pyridine-2,6-dicarbonyl dichloride as antimicrobial agents.

    PubMed

    Al-Salahi, Rashad A; Al-Omar, Mohamed A; Amr, Abd El-Galil E

    2010-09-20

    A series of chiral linear and macrocyclic bridged pyridines has been prepared starting from pyridine-2,6-dicarbonyl dichloride (2). The coupling of 1 with D-alanyl methyl ester gave 2,6-bis-D-alanyl pyridine methyl ester (3). Hydrazinolysis of 3 with hydrazine hydrate afforded bis-hydrazide 4. The latter was reacted with thiophene-2-carbaldehyde, phthalic anhydride or cyclohexanone to afford bis-carboxamide pyridine derivatives 5-7, respectively. Compound 4 was coupled with p-methoxy- or p-nitroaceto-phenone to yield compounds 8 and 9. In addition, 4 was reacted with 1,2,4,5-benzenetetra-carboxylic acid dianhydride or 1,4,5,8-naphthalenetetracarboxylic acid dianhydride to afford the macrocyclic octacarboxaamide pyridines 10 and 11. The detailed synthesis, spectroscopic data and antimicrobial screening for the synthesized compounds are reported.

  3. Correlation between Levels of 2, 5-Hexanedione and Pyrrole Adducts in Tissues of Rats Exposure to n-Hexane for 5-Days

    PubMed Central

    Yin, Hongyin; Guo, Ying; Zeng, Tao; Zhao, Xiulan; Xie, Keqin

    2013-01-01

    Background The formation of pyrrole adducts might be responsible for peripheral nerve injury caused by n-hexane. The internal dose of pyrrole adducts would supply more information for the neurotoxicity of n-hexane. The current study was designed to investigate the tissue distributions of 2, 5-hexanedione (2,5-HD) and pyrrole adducts in rats exposed to n-hexane, and analyze the correlation between pyrrole adducts and 2,5-HD in tissues. Methods Male Wistar rats were given daily dose of 500,1000, 2000, 4000 mg/kg bw n-hexane by gavage for 5 days. The rats were sacrificed 24 hours after the last administration. The levels of 2, 5-hexanedione and pyrrole adducts in tissues were measured by gas chromatography and Ehrlich’s reagent, respectively. The correlations between 2, 5-hexanedione and pyrrole adducts were analyzed by linear regression Results Dose-dependent effects were observed between the dosage of n-hexane and 2, 5-hexanedione, and pyrrole adducts in tissues. The highest level of 2, 5-hexanedione was found in urine and the lowest in sciatic nerve, while the highest level of pyrrole adducts was seen in liver and the lowest in serum. There were significant correlations among the free 2, 5-hexanedione, total 2, 5-hexanedione and pyrrole adducts within the same tissues. Pyrrole adducts in serum showed the most significant correlation with free 2, 5-hexanedione or pyrrole adducts in tissues. Conclusion The findings suggested that pyrrole adducts in serum might be a better indicator for the internal dose of free 2, 5-hexanedione and pyrrole adducts in tissues. PMID:24098756

  4. Synthesis, crystal structure, characterization and biological activity of 2,5-hexanedione bis(isonicotinylhydrazone) and N-(2,5-dimethyl-1H-pyrrol-1-yl)isonicotinamide complexes.

    PubMed

    Jeragh, Bakir; Ali, Mayada S; El-Asmy, Ahmed A

    2015-01-01

    The reaction between 2,5-hexanedione and isonicotinic acid hydrazide in EtOH gave two products. The ethanol insoluble product was identified as 2,5-hexanedione bis(isonicotinylhydrazone) [HINH] and the soluble ethanol product as N-(2,5-dimethyl-1H-pyrrol-1-yl)isonicotinamide [DINA]. A series of Cr(3+), Fe(3+), Co(2+), Ni(2+), Cu(2+), Zn(2+), Cd(2+), Hg(2+) and Pd(2+) complexes of HINH and Co(2+), Cu(2+), Zn(2+) and Hg(2+) complexes of DINA have been synthesized and structurally characterized. Based on the elemental analysis, mass spectra and molar conductance, the complexes have assigned the proposed imperical formulae. The crystal structures of N-(2,5-dimethyl-1H-pyrrol-1-yl)isonicotinamide and its Zn(2+) and Hg(2+) complexes have been solved by X-ray diffraction having [Zn(DINA)2Cl2] and [Hg(DINA)2Cl2] in a tetrahedral structure. In the DINH complexes, the ligand coordinates as a monodentate through the pyridine nitrogen. On the other hand, HINH behaves as a tetradentate (neutral or binegative) manner with the two metal ions. The magnetic moments and electronic spectra of all complexes provide tetrahedral, square-planar, trigonal biyramid and/or octahedral structure. The thermal decomposition of the complexes revealed the outer and inner solvents as well as the end product. The steady part of [Zn(DINA)2Cl2] and [Hg(DINA)2Cl2] thermograms till 303 and 286 °C indicates the absence of any outside solvents. All compounds have activity against bacteria more than fungi. [Cd4(HINH)Cl8]·3H2O has the highest values.

  5. Reaction of allenyl esters with sodium azide: an efficient synthesis of e-vinyl azides and polysubstituted pyrroles.

    PubMed

    Huang, Xian; Shen, Ruwei; Zhang, Tiexin

    2007-02-16

    The nucleophilic addition of sodium azide to 1,2-allenyl esters can generate vinyl azides in excellent yields with excellent regio- and stereoselectivities. Moreover, pyrroles are synthesized using 1-allyllic 1,2-allenyl esters as substrates in t-BuOH at 65 degrees C. The sequential reaction for pyrroles is developed on the basis of a novel domino process involving nucleophilic addition, cycloaddition, denitrogenation, and aromatization.

  6. H₈-BINOL chiral imidodiphosphoric acid catalyzed highly enantioselective aza-Friedel-Crafts reactions of pyrroles and enamides/imines.

    PubMed

    Wu, Kun; Zhuo, Ming-Hua; Sha, Di; Fan, Yan-Sen; An, Dong; Jiang, Yi-Jun; Zhang, Suoqin

    2015-05-11

    The first enantioselective aza-Friedel-Crafts reaction between pyrroles and enamides has been achieved by using a novel H8-BINOL-type imidodiphosphoric acid catalyst. This methodology was also applied to the highly enantioselective aza-Friedel-Crafts reaction between pyrroles and imines. The catalyst loadings in these two reactions are low (0.3-2 mol%). Both processes are amenable to gram scales.

  7. Photochemistry of o-pyrrolylstilbenes and formation of spiro-2H-pyrroles and their rearrangement to dihydroindoles.

    PubMed

    Basarić, Nikola; Marinić, Eljko; Sindler-Kulyk, Marija

    2006-12-08

    Excited states of stilbenylpyrroles 1a-1c deactivate by two photochemical processes: cis-trans-isomerization and hydrogen transfer of NH to the stilbene double bond. NH-transfer results in the formation of two quinone dimethane intermediates, 10 and 11, and biradicals 12. Intramolecular cyclization of intermediates 10-12 gives rise to polycyclic compounds spiro-2H-pyrroles 7, pyrroloisoindoles 3, and pyrroloisoquinolines 8. Spiro-2H-pyrroles 7 rearrange on silica gel, giving dihydroindoles 2.

  8. Pyrrole oxidation and protein cross-linking as necessary steps in the development of gamma-diketone neuropathy.

    PubMed

    Genter St Clair, M B; Amarnath, V; Moody, M A; Anthony, D C; Anderson, C W; Graham, D G

    1988-01-01

    It has been well documented that the gamma-diketone HD1 is the ultimate toxic metabolite of n-hexane. Furthermore, it has been shown that the pathogenetic mechanism by which HD exerts its neurotoxic effects is through binding to protein lysly residues and cyclization to pyrroles. The present study sought to determine whether the presence of pyrrole residues on NF1 proteins is sufficient to cause the NF-filled axonal swellings associated with n-hexane and other gamma-diketone neuropathies or whether pyrrole oxidation and protein cross-linking also have to occur in order for neurotoxicity to develop. We synthesized the HD analogue AcHD1 and assessed its rate of pyrrole formation in vitro, the ease of oxidation of its resulting pyrroles, and its ability to cross-link proteins in vitro. The in vivo effects of AcHD on rats were examined following daily ip1 injections. AcHD was found to have a rate of pyrrole formation comparable to that of the potent HD analogue DMHD1 at 35 degrees C. The pyrrole derived from AcHD was more resistant to oxidation than that derived from the neurotoxic compound HD. AcHD did not cross-link proteins in vitro. Pyrrole derivatives were demonstrated on hemoglobin isolated from animals treated with HD, DMHD, and AcHD. Cross-linked spectrin was detected in animals treated with HD and DMHD but not with AcHD. Rats receiving 0.1 or 0.25 mmol of AcHD/kg/day did not reach the end point of hindlimb paralysis observed in the gamma-diketone neuropathies, and the NF-filled axonal swellings seen following exposure to the neurotoxic gamma-diketones were not observed.(ABSTRACT TRUNCATED AT 250 WORDS)

  9. Ruthenium(II)-Catalyzed C-H Activation of Imidamides and Divergent Couplings with Diazo Compounds: Substrate-Controlled Synthesis of Indoles and 3H-Indoles.

    PubMed

    Li, Yunyun; Qi, Zisong; Wang, He; Yang, Xifa; Li, Xingwei

    2016-09-19

    Indoles are an important structural motif that is commonly found in biologically active molecules. In this work, conditions for divergent couplings between imidamides and acceptor-acceptor diazo compounds were developed that afforded NH indoles and 3H-indoles under ruthenium catalysis. The coupling of α-diazoketoesters afforded NH indoles by cleavage of the C(N2 )-C(acyl) bond whereas α-diazomalonates gave 3H-indoles by C-N bond cleavage. This reaction constitutes the first intermolecular coupling of diazo substrates with arenes by ruthenium-catalyzed C-H activation.

  10. Pyridine-grafted chitosan derivative as an antifungal agent.

    PubMed

    Jia, Ruixiu; Duan, Yunfei; Fang, Qiang; Wang, Xiangyang; Huang, Jianying

    2016-04-01

    Pyridine moieties were introduced into chitosan by nucleophilic substitution to afford N-(1-carboxybutyl-4-pyridinium) chitosan chloride (pyridine chitosan). The resulting chitosan derivative was well characterized, and its antifungal activity was examined, based on the inhibition of mycelial growth and spore germination. The results indicated that pyridine chitosan exhibited enhanced antifungal activity by comparison with pristine chitosan. The values of the minimum inhibitory concentration and the minimal fungicidal concentration of pyridine chitosan against Fulvia fulva were 0.13 mg/ml and 1 mg/ml, respectively, while the corresponding values against Botrytis cinerea were 0.13 mg/ml and 4 mg/ml, respectively. Severe morphological changes of pyridine chitosan-treated B. cinerea were observed, indicative that pyridine chitosan could damage and deform the structure of fungal hyphae and subsequently inhibit strain growth. Non-toxicity of pyridine chitosan was demonstrated by an acute toxicity study. These results are beneficial for assessing the potential utilization of this chitosan derivative and for exploring new functional antifungal agents with chitosan in the food industry.

  11. 4-[(E)-2-(Pyridin-2-yl)ethen-yl]pyridine-terephthalic acid (2/1).

    PubMed

    Castro-Montes, Paola; Guerrero-Alvarez, Jorge A; Hopfl, Herbert; Campos-Gaxiola, Jose J; Cruz-Enriquez, Adriana

    2012-12-01

    The title 2:1 co-crystal, 2C12H10N2·C8H6O4, crystallizes with one mol-ecule of 4-[(E)-2-(pyridin-2-yl)ethen-yl]pyridine (A) and one half-mol-ecule of terephthalic acid (B) in the asymmetric unit. In the crystal, the components are linked through heterodimeric COOH⋯Npyridine synthons, forming linear aggregates of composition -A-B-A-B-. Further linkage through weak C-H⋯O and C-H⋯π inter-actions gives two-dimensional hydrogen-bonded undulating sheets propagating in the [100] and [010] directions. These layers are connected through additional weak C-H⋯O contacts, forming a three-dimensional structure.

  12. Low-Dose Radiotherapy in Indolent Lymphoma

    SciTech Connect

    Rossier, Christine; Schick, Ulrike; Miralbell, Raymond; Mirimanoff, Rene O.; Weber, Damien C.; Ozsahin, Mahmut

    2011-11-01

    Purpose: To assess the response rate, duration of response, and overall survival after low-dose involved-field radiotherapy in patients with recurrent low-grade lymphoma or chronic lymphocytic leukemia (CLL). Methods and Materials: Forty-three (24 women, 19 men) consecutive patients with indolent lymphoma or CLL were treated with a total dose of 4 Gy (2 x 2 Gy) using 6- 18-MV photons. The median age was 73 years (range, 39-88). Radiotherapy was given either after (n = 32; 75%) or before (n = 11; 25%) chemotherapy. The median time from diagnosis was 48 months (range, 1-249). The median follow-up period was 20 months (range, 1-56). Results: The overall response rate was 90%. Twelve patients (28%) had a complete response, 15 (35%) had a partial response, 11 (26%) had stable disease, and 5 (11%) had progressive disease. The median overall survival for patients with a positive response (complete response/partial response/stable disease) was 41 months; for patients with progressive disease it was 6 months (p = 0.001). The median time to in-field progression was 21 months (range, 0-24), and the median time to out-field progression was 8 months (range, 0-40). The 3-year in-field control was 92% in patients with complete response (median was not reached). The median time to in-field progression was 9 months (range, 0.5-24) in patients with partial response and 6 months (range, 0.6-6) in those with stable disease (p < 0.05). Younger age, positive response to radiotherapy, and no previous chemotherapy were the best factors influencing the outcome. Conclusions: Low-dose involved-field radiotherapy is an effective treatment in the management of patients with recurrent low-grade lymphoma or CLL.

  13. Pyrrolo[3,2-b]pyrroles – from unprecedented solvatofluorochromism to two-photon absorption

    PubMed Central

    Friese, Daniel H.; Mikhaylov, Alexander; Krzeszewski, Maciej; Poronik, Yevgen M.

    2015-01-01

    A combined experimental and theoretical study of the two-photon absorption properties of a series of quadrupolar molecules possessing a highly electron-rich heterocyclic core, pyrrolo[3,2-b]pyrrole is presented. In agreement with quantum-chemical calculations, we observe large two-photon absorption (2PA) cross-section values, σ2PA ~ 102–103 GM (1GM = 1050 cm4 s photon−1) at wavelengths 650–700 nm, corresponding to the 2-photon allowed but 1-photon forbidden transitions. The calculations also predict that increased planarity of this molecule via removal of two N-substituents leads to further increase in the σ2PA values. Surprisingly, the most quadrupolar pyrrolo[3,2-b]pyrrole derivative bearing two 4-nitrophenyl substituents at positions 2 and 5 demonstrates very strong solvatofluorochromic effect, with the fluorescence quantum yield as high as 0.96 in cyclohexane, while the fluorescence vanishes in DMSO. PMID:26511232

  14. Ab initio multiple cloning simulations of pyrrole photodissociation: TKER spectra and velocity map imaging

    DOE PAGES

    Makhov, Dmitry V.; Saita, Kenichiro; Martinez, Todd J.; ...

    2014-12-11

    In this study, we report a detailed computational simulation of the photodissociation of pyrrole using the ab initio Multiple Cloning (AIMC) method implemented within MOLPRO. The efficiency of the AIMC implementation, employing train basis sets, linear approximation for matrix elements, and Ehrenfest configuration cloning, allows us to accumulate significant statistics. We calculate and analyze the total kinetic energy release (TKER) spectrum and Velocity Map Imaging (VMI) of pyrrole and compare the results directly with experimental measurements. Both the TKER spectrum and the structure of the velocity map image (VMI) are well reproduced. Previously, it has been assumed that the isotropicmore » component of the VMI arises from long time statistical dissociation. Instead, our simulations suggest that ultrafast dynamics contributes significantly to both low and high energy portions of the TKER spectrum.« less

  15. Ab initio multiple cloning simulations of pyrrole photodissociation: TKER spectra and velocity map imaging.

    PubMed

    Makhov, Dmitry V; Saita, Kenichiro; Martinez, Todd J; Shalashilin, Dmitrii V

    2015-02-07

    We report a detailed computational simulation of the photodissociation of pyrrole using the ab initio Multiple Cloning (AIMC) method implemented within MOLPRO. The efficiency of the AIMC implementation, employing train basis sets, linear approximation for matrix elements, and Ehrenfest configuration cloning, allows us to accumulate significant statistics. We calculate and analyze the total kinetic energy release (TKER) spectrum and Velocity Map Imaging (VMI) of pyrrole and compare the results directly with experimental measurements. Both the TKER spectrum and the structure of the velocity map image (VMI) are well reproduced. Previously, it has been assumed that the isotropic component of the VMI arises from long time statistical dissociation. Instead, our simulations suggest that ultrafast dynamics contributes significantly to both low and high energy portions of the TKER spectrum.

  16. New pentasubstituted pyrrole hybrid atorvastatin-quinoline derivatives with antiplasmodial activity.

    PubMed

    Carvalho, Rita C C; Martins, Wagner A; Silva, Tayara P; Kaiser, Carlos R; Bastos, Mônica M; Pinheiro, Luiz C S; Krettli, Antoniana U; Boechat, Núbia

    2016-04-15

    Cerebral malaria is caused by Plasmodium falciparum. Atorvastatin (AVA) is a pentasubstituted pyrrole, which has been tested as an adjuvant in the treatment of cerebral malaria. Herein, a new class of hybrids of AVA and aminoquinolines (primaquine and chloroquine derivatives) has been synthesized. The quinolinic moiety was connected to the pentasubstituted pyrrole from AVA by a linker group (CH2)n=2-4 units. The activity of the compounds increased with the size of the carbons chain. Compound with n=4 and 7-chloroquinolinyl has displayed better activity (IC50=0.40 μM) than chloroquine. The primaquine derivative showed IC50=1.41 μM, being less toxic and more active than primaquine.

  17. Atomic force microscope characterization of self-assembly behaviors of cyclo[8] pyrrole on solid substrates

    NASA Astrophysics Data System (ADS)

    Xu, Hai; Zhao, Siqi; Xiong, Xiang; Jiang, Jinzhi; Xu, Wei; Zhu, Daoben; Zhang, Yi; Liang, Wenjie; Cai, Jianfeng

    2017-04-01

    Cyclo [8] pyrrole (CP) is a porphyrin analogue containing eight α-conjugated pyrrole units which are arranged in a nearly coplanar conformation. The π-π interactions between CP molecules lead to regular aggregations through a solution casting process. Using tapping mode atomic force microscope (AFM), we investigated the morphology of self-assembled aggregates formed by deposition of different CP solutions on different substrates. We found that in the n-butanol solution, nanofibrous structures could be formed on the silicon or mica surface. Interestingly, on the highly oriented pyrolytic graphite (HOPG) surface, or silicon and mica surface with a toluene solution, only irregular spherical structures were identified. The difference in the nanomorphology may be attributed to distinct interactions between molecule-molecule, molecule-solvent and molecule-substrate.

  18. Structure-activity relationship of pyrrole based S-nitrosoglutathione reductase inhibitors: carboxamide modification.

    PubMed

    Sun, Xicheng; Qiu, Jian; Strong, Sarah A; Green, Louis S; Wasley, Jan W F; Blonder, Joan P; Colagiovanni, Dorothy B; Stout, Adam M; Mutka, Sarah C; Richards, Jane P; Rosenthal, Gary J

    2012-03-15

    The enzyme S-nitrosoglutathione reductase (GSNOR) is a member of the alcohol dehydrogenase family (ADH) that regulates the levels of S-nitrosothiols (SNOs) through catabolism of S-nitrosoglutathione (GSNO). GSNO and SNOs are implicated in the pathogenesis of many diseases including those in respiratory, gastrointestinal, and cardiovascular systems. The pyrrole based N6022 was recently identified as a potent, selective, reversible, and efficacious GSNOR inhibitor which is currently in clinical development for acute asthma. We describe here the synthesis and structure-activity relationships (SAR) of novel pyrrole based analogs of N6022 focusing on carboxamide modifications on the pendant N-phenyl moiety. We have identified potent and novel GSNOR inhibitors that demonstrate efficacy in an ovalbumin (OVA) induced asthma model in mice.

  19. Langmuir-Blodgett films of a pyrrole and ferrocene mixed surfactant system

    SciTech Connect

    Samuelson, L.; Rahman, A.K.M.; Clough, S.; Tripathy, S.; Hale, P.D.; Inagaki, T.; Skotheim, T.A.; Okamoto, Y. . Dept. of Chemistry; Brookhaven National Lab., Upton, NY; Polytechnic Univ., Brooklyn, NY . Dept. of Chemistry)

    1989-01-01

    The Langmuir-Blodgett technique was used to study the molecular organization of a mixed 3-hexadecyl pyrrole (3HDP) and ferrocene-derivatized pyrrole (Fc-Py) surfactant system. It has been determined that stable monolayer films of the mixed system could be formed at the air-water interface. The growth and assembly process led to polypyrrole 2-D lattices with heretofore unsurpassed order. In fact, the process of template polymerization, it appears, leads to a new crystal phase for the polypyrrole component of the thin film structure. Various monolayer and multilayer films were prepared on platinum coated substrates for surface spectroscopic characterization. Near Edge X-Ray Absorption Fine Structure (NEXAFS) studies revealed that highly ordered multilayer structures are being formed. Electrochemical studies have been initiated to determine the feasibility of these films in molecular electronic device applications. 13 refs., 6 figs., 1 tab.

  20. Ternatusine A, a new pyrrole derivative with an epoxyoxepino ring from Ranunculus ternatus.

    PubMed

    Zhan, Zhilai; Feng, Ziming; Yang, Yanan; Li, Li; Jiang, Jianshuang; Zhang, Peicheng

    2013-04-19

    Ternatusine A (1), a novel alkaloid with an unprecedented epoxyoxepino[4,5-c] pyrrole ring, was isolated from the roots of Ranunculus ternatus Thunb. Its unusual structure, including its absolute stereochemistry, was determined using UV, IR, HRESIMS, and 1D and 2D NMR data and through comparison of the experimental and calculated electronic circular dichroism (ECD) spectra. A possible biosynthetic pathway for ternatusine A was postulated.

  1. Interaction of the cesium cation with meso-octamethylcalix[4]pyrrole: Experimental and theoretical study

    NASA Astrophysics Data System (ADS)

    Polášek, Miroslav; Makrlík, Emanuel; Kvíčala, Jaroslav; Křížová, Věra; Petr Vaňura

    2017-02-01

    By using electrospray ionization mass spectrometry (ESI-MS), it was proven experimentally that the univalent cesium cation (Cs+) forms with meso-octamethylcalix[4]pyrrole (abbrev. 1) the cationic complex species 1.Cs+. Further, applying quantum chemical DFT calculations, four different conformations of the resulting complex 1.Cs+ were derived. It means that under the present experimental conditions, this ligand 1 can be considered as a macrocyclic receptor for the cesium cation.

  2. Inhibition of endotoxin-induced airway epithelial cell injury by a novel family of pyrrol derivates.

    PubMed

    Cabrera-Benítez, Nuria E; Pérez-Roth, Eduardo; Ramos-Nuez, Ángela; Sologuren, Ithaisa; Padrón, José M; Slutsky, Arthur S; Villar, Jesús

    2016-06-01

    Inflammation and apoptosis are crucial mechanisms for the development of the acute respiratory distress syndrome (ARDS). Currently, there is no specific pharmacological therapy for ARDS. We have evaluated the ability of a new family of 1,2,3,5-tetrasubstituted pyrrol compounds for attenuating lipopolysaccharide (LPS)-induced inflammation and apoptosis in an in vitro LPS-induced airway epithelial cell injury model based on the first steps of the development of sepsis-induced ARDS. Human alveolar A549 and human bronchial BEAS-2B cells were exposed to LPS, either alone or in combination with the pyrrol derivatives. Rhein and emodin, two representative compounds with proven activity against the effects of LPS, were used as reference compounds. The pyrrol compound that was termed DTA0118 had the strongest inhibitory activity and was selected as the lead compound to further explore its properties. Exposure to LPS caused an intense inflammatory response and apoptosis in both A549 and BEAS-2B cells. DTA0118 treatment downregulated Toll-like receptor-4 expression and upregulated nuclear factor-κB inhibitor-α expression in cells exposed to LPS. These anti-inflammatory effects were accompanied by a significantly lower secretion of interleukin-6 (IL-6), IL-8, and IL-1β. The observed antiapoptotic effect of DTA0118 was associated with the upregulation of antiapoptotic Bcl-2 and downregulation of proapoptotic Bax and active caspase-3 protein levels. Our findings demonstrate the potent anti-inflammatory and antiapoptotic properties of the pyrrol DTA0118 compound and suggest that it could be considered as a potential drug therapy for the acute phase of sepsis and septic ARDS. Further investigations are needed to examine and validate these mechanisms and effects in a clinically relevant animal model of sepsis and sepsis-induced ARDS.

  3. Cationic vinyl pyridine copolymers and products thereof

    NASA Technical Reports Server (NTRS)

    Rembaum, Alan (Inventor)

    1978-01-01

    Quaternized, cross-linked, insoluble copolymers of unsubstituted and substituted vinyl pyridines and a dihalo organic compound are spontaneously formed at ambient temperature on mixing the two monomers in bulk, in solution or in suspension. The amount of cross-linking may be varied according to the composition and reaction conditions. The polymer product exhibits ion exchange capacity and undergoes a reversible color change from black at a pH above 7 to yellow at a pH below 7. The polymer may be formed in the presence of preformed polymers, substrates such as porous or impervious particles or films to deposit an ion exchange film in situ or on the surface of the substrate. The coated or resin impregnated substrate may be utilized for separation of anionic species from aqueous solution.

  4. An amperometric urea biosensor based on covalent immobilization of urease onto an electrochemically prepared copolymer poly (N-3-aminopropyl pyrrole-co-pyrrole) film.

    PubMed

    Rajesh; Bisht, Vandana; Takashima, Wataru; Kaneto, Keiichi

    2005-06-01

    An amperometric biosensor has been developed for the quantitative determination of urea in aqueous solution. The principle is based on the use of pH-sensitive redox active dissolved hematein molecule. The enzyme, urease (Urs), was covalently immobilized on a conducting copolymer poly (N-3-aminopropyl pyrrole-co-pyrrole) film, electrochemically prepared onto an indium-tin-oxide (ITO)-coated glass plate. The covalent linkage of enzyme and porous morphology of the polymer film lead to high enzyme loading and an increased lifetime stability of the enzyme electrode. Amperometric response was measured as a function of concentration of urea, at fixed bias voltage of 0.0 V vs. Ag/AgCl in a phosphate buffer (pH 7.0). The electrode gives a linear response range of 0.16-5.02 mM for urea in aqueous medium. The response time is 40 s reaching to a 95% steady-state current value, and 80% of the enzyme activity is retained for about 2 months.

  5. Evaluation on the inhibition of pyrrol-2-yl ethanone derivatives to lactate dehydrogenase and anticancer activities

    NASA Astrophysics Data System (ADS)

    Lu, Na-Na; Weng, Zhao-Yue; Chen, Qiu-Yun; Boison, Daniel; Xiao, Xin-Xin; Gao, Jing

    2016-08-01

    Lactate dehydrogenase A (LDH-A) is a potentially important metabolic target for the inhibition of the highly activated glycolysis pathway in cancer cells. In order to develop bifunctional compounds as inhibitor of LDH-A and anticancer agents, two pyrrol-2-yl methanone (or ethanone) derivatives (PM1 and PM2) were synthesized and evaluated as inhibitors of LDH-A based on the enzyme assay and cell assay by spectroscopy analysis. Fluorescence and CD spectra results demonstrated that both the change of second structure of LDH-A and the affinity interaction for compounds to LDH-A gave great effect on the activity of LDH-A. In particular, low concentration of compounds (1 μμ-25 μμ) could change the level of pyruvate in cancer cells. Moreover, the in vitro assay results demonstrated that pyrrol-2-yl ethanone derivatives can inhibit the proliferation of cancer cells. Therefore, pyrrol-2-yl ethanone derivatives (PM2) can be both LDH-A inhibitor and anticancer agents.

  6. Ferroelectric switching and electrochemistry of pyrrole substituted trialkylbenzene‐1,3,5‐tricarboxamides

    PubMed Central

    Meng, Xiao; Gorbunov, Andrey V.; Christian Roelofs, W. S.; Meskers, Stefan C. J.; Janssen, René A. J.; Kemerink, Martijn

    2017-01-01

    ABSTRACT We explore a new approach to organic ferroelectric diodes using a benzene‐tricarboxamide (BTA) core connected with C10 alkyl chains to pyrrole groups, which can be polymerized to provide a semiconducting ferroelectric material. The compound possesses a columnar hexagonal liquid crystalline (LC) phase and exhibits ferroelectric switching. At low switching frequencies, an additional process occurs, which leads to a high hysteretic charge density of up to ∼1000 mC/m2. Based on its slow rate, the formation of gas bubbles, and the emergence of characteristic polypyrrole absorption bands in the UV–Vis–NIR, the additional process is identified as the oxidative polymerization of pyrrole groups, enabled by the presence of amide groups. Polymerization of the pyrrole groups, which is essential to obtain semiconductivity, is limited to thin layers at the electrodes, amounting to ∼17 nm after cycling for 21 h. © 2017 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2017, 55, 673–683 PMID:28344384

  7. Effects of a pyrrole-based, microtubule-depolymerizing compound on RAW 264.7 macrophages.

    PubMed

    Ciemniecki, John A; Lewis, Clarke P; Gupton, John T; Fischer-Stenger, Krista

    2016-02-25

    RAW 264.7 murine macrophages were exposed to the pyrrole-based compound 3,5-Dibromo-4-(3,4-dimethoxyphenyl)-1H-pyrrole-2-carboxylic acid ethyl ester (JG-03-14), which is a known microtubule depolymerizing agent with antitumor activity [1,2,3]. In this study exposure to JG-03-14 reduced the production of pro-inflammatory molecules by macrophages activated with lipopolysaccharide (LPS). Treatment with the pyrrole-based compound decreased the concentration of tumor necrosis factor-α (TNF-α) and nitric oxide (NO) released from the macrophages. Exposure to JG-03-14 also decreased TNF-α mRNA expression levels and the protein expression levels of inducible nitric oxide synthase (iNOS), the enzyme responsible for NO production in the activated macrophages. Furthermore, JG-03-14 treatment significantly changed the degradation profile of IκB-β, an inhibitor of the NF-κB transcription factor, which suggests that JG-03-14 may attenuate the activation of the LPS-induced NF-κB signaling pathway needed to produce the pro-inflammatory mediators. We conclude that JG-03-14 possesses anti-inflammatory properties.

  8. Electrochemical synthesis of poly(pyrrole-co-o-anisidine)/chitosan composite films

    NASA Astrophysics Data System (ADS)

    Yalçınkaya, Süleyman; Çakmak, Didem

    2017-05-01

    In this study, poly(pyrrole-co-o-anisidine)/chitosan composite films were electrochemically synthesized in various monomers feed ratio (pyrrole: o-anisidine; 9:1, 7:3, 1:1, 3:7 and 1:9) of pyrrole and o-anisidine on the platinum electrode. Electrochemical synthesis of the composite films was carried out via cyclic voltammetry technique. They were characterized by FT-IR, cyclic voltammetry, SEM micrographs, digital images, TGA and DSC techniques. The SEM results indicated that the particle size of the composite decreased with increasing o-anisidine ratio and the films became more likely to be smooth morphology. The TGA results proved that the film of the composite with 1:1 ratio showed highest final degradation temperature and lowest weight loss (83%) compared to copolymer and 9:1 1:9 composite films. The 1:1 composite film had higher thermal stability than copolymer and the other composite films (9:1 1:9). Meanwhile, electrochemical studies exhibited that the 1/9 composite film had good electrochemical stability as well.

  9. Absolute intensities of NH-stretching transitions in dimethylamine and pyrrole.

    PubMed

    Miller, Benjamin J; Du, Lin; Steel, Thomas J; Paul, Allanah J; Södergren, A Helena; Lane, Joseph R; Henry, Bryan R; Kjaergaard, Henrik G

    2012-01-12

    Vibrational spectra of vapor-phase dimethylamine (DMA) and pyrrole have been recorded in the 1000 to 13000 cm(-1) region using long path conventional spectroscopy techniques. We have focused on the absolute intensities of the NH-stretching fundamental and overtone transitions; Δν(NH) = 1-4 regions for DMA and the Δν(NH) = 1-3 regions for pyrrole. In the Δν(NH) = 1-3 regions for DMA, evidence of tunneling splitting associated with the NH-wagging mode is observed. For DMA, the fundamental NH-stretching transition intensity is weaker than the first NH-stretching overtone. Also, the fundamental NH-stretching transition in DMA is much weaker than the fundamental transition in pyrrole. We have used an anharmonic oscillator local mode model with ab initio calculated local mode parameters and dipole moment functions at the CCSD(T)/aug-cc-pVTZ level to calculate the NH-stretching intensities and explain this intensity anomaly in DMA.

  10. Novel pyrrole derivatives bearing sulfonamide groups: Synthesis in vitro cytotoxicity evaluation, molecular docking and DFT study

    NASA Astrophysics Data System (ADS)

    Bavadi, Masoumeh; Niknam, Khodabakhsh; Shahraki, Omolbanin

    2017-10-01

    The synthesis of new derivatives of pyrrole substituted sulfonamide groups is described. The in vitro anticancer activity of these pyrroles was evaluated against MCF7, MOLT-4 and HL-60 cells using MTT assay. The target compounds showed inhibitory activity against tested cell lines. Among the compounds, compound 1a exhibited good cytotoxic activity. The potential of this analog to induce apoptosis was confirmed in a nuclear morphological assay by Hoechst 33258 staining in the PC-12 cells. Finally, molecular docking was performed to determine the probable binding mode of the designed pyrrole derivatives into the active site of FGFR1 protein. DFT calculations were carried out at the B3LYP levels of theory with 6-31+G (d,p) basis set for compound 1a. The point group (C1) of it was obtained based on the optimized structures; the calculation of the FT-IR vibrational frequencies, 1H NMR and 13C NMR chemical shifts of the compound were carried out and compared with those obtained experimentally.

  11. A reinterpretation of the electronic spectrum of pyrrole: A quantum dynamics study

    SciTech Connect

    Neville, S. P.; Worth, G. A.

    2014-01-21

    The first band in the electronic spectrum of pyrrole is calculated from wavepacket propagations performed using the MCTDH method. To do so, two model Hamiltonians are constructed to describe seven low-lying excited electronic states of pyrrole. These Hamiltonians are based on the vibronic coupling model, and are parameterised via fitting to extensive CASPT2 and EOM-CCSD calculations. A detailed analysis of the structure of pyrrole's electronic spectrum in the range 5.5 to 6.5 eV is made. The role of intensity borrowing from transitions to ππ{sup *} states by lower-lying 3s and 3p Rydberg states is assessed, and reassignments of much of the spectrum are subsequently made which indicate that most of the states in the spectrum are predominantly Rydberg in character. The resulting conclusions drawn serve to highlight the limitations of assignments based on the matching of calculated vertical excitation energies and the positions of peak maxima observed in electronic spectra.

  12. ESI-MS Characterization of a Novel Pyrrole-Inosine Nucleoside that Interacts with Guanine Bases

    PubMed Central

    Pierce, Sarah E.; Sherman, Courtney L.; Jayawickramarajah, Janarthanan; Lawrence, Candace M.; Sessler, Jonathan L.; Brodbelt, Jennifer S.

    2008-01-01

    Based on binding studies undertaken by electrospray ionization-mass spectrometry, a synthetic pyrrole-inosine nucleoside, 1, capable of forming an extended three-point Hoogsteen-type hydrogen-bonding interaction with guanine, is shown to form specific complexes with two different quadruplex DNA structures [dTG4T]4 and d(T2G4)4 as well as guanine rich duplex DNA. The binding interactions of two other analogs were evaluated in order to unravel the structural features that contribute to specific DNA recognition. The importance of the Hoogsteen interactions was confirmed through the absence of specific binding when the pyrrole NH hydrogen-bonding site was blocked or removed. While 2, with a large blocking group, was not found to interact with virtually any form of DNA, 3, with the pyrrole functionality missing, was found to interact non-specifically with several types of DNA. The specific binding of 1 to guanine rich DNA emphasizes the necessity of careful ligand design for specific sequence recognition. PMID:18790136

  13. Is papillary thyroid microcarcinoma an indolent tumor?

    PubMed Central

    Gao, Xuemei; Zhang, Xiao; Zhang, Yajing; Hua, Wenjuan; Maimaiti, Yusufu; Gao, Zairong

    2016-01-01

    Abstract The increasing detection of papillary thyroid microcarcinoma (PTMC) has created management dilemmas. To clarify the clinical significance of postsurgery stimulated thyroglobulin (ps-Tg) in PTMC who undergo thyroidectomy and radioactive iodine (RAI), we retrospectively reviewed the 358 PTMC patients who were treated with RAI and followed up in our hospital. Those with an excessive anti-Tg antibody, ultrasound-detected residual were excluded, thereby resulting in the inclusion of 280 cases. Their clinical and histopathological information and clinical outcomes were collected and summarized. Tumor stages were classified according to the tumor, node, metastasis (TNM) staging system and the consensus of the European Thyroid Association (ETA) risk stratification system, respectively. Kaplan–Meier curves were constructed to compare the disease-free survival (DFS) rates of different risk-staging systems. By the end of follow-up, none of the patients died of the disease or relapsed. The 8-year DFS rate was 76.9%. Kaplan–Meier curves showed different DFS rates in TNM stages I versus IV, III versus IV, very low risk versus high risk, low risk versus high risk, respectively (P < 0.05), while they were not significantly different in stage I versus stage III, very low risk versus low risk (P > 0.05). Finally, 40 (14.3%) cases got a persistent disease. Five variables (male sex, nonconcurrent benign pathology, initial tumor size >5 mm, lymph node metastasis, and ps-Tg ≥ 10 μg/L) were associated with disease persistence by univariate regression analysis. Ps-Tg ≥ 10 μg/L was the only independent prognostic variable that predicted disease persistence by multivariate regression analysis (odds ratio: 36.057, P = 0.000). Therefore, PTMC with a small size of ≤1 cm does not always act as an indolent tumor. In conclusion, ps-Tg ≥ 10 μg/L is associated with increased odds of disease persistence. ETA risk stratification is more

  14. Indole Localization in Lipid Membranes Revealed by Molecular Simulation

    PubMed Central

    Norman, Kristen E.; Nymeyer, Hugh

    2006-01-01

    It is commonly known that the amino acid residue tryptophan and its side-chain analogs, e.g., indole, are strongly attracted to the interfacial region of lipid bilayers. Phenylalanine and its side-chain analogs, e.g., benzene, do not localize in the interface but are distributed throughout the lipid bilayer. We use molecular dynamics to investigate the details of indole and benzene localization and orientation within a POPC bilayer and the factors that lead to their different properties. We identify three sites in the bilayer at which indole is localized: 1), a site in the interface near the glycerol moiety; 2), a weakly bound site in the interface near the choline moiety; and 3), a weakly bound site in the center of the bilayer's hydrocarbon core. Benzene is localized in the same three positions, but the most stable position is the hydrocarbon core followed by the site near the glycerol moiety. Transfer of indole from water to the hydrocarbon core shows a classic hydrophobic effect. In contrast, interfacial binding is strongly enthalpy driven. We use several different sets of partial charges to investigate the factors that contribute to indole's and benzene's orientational and spatial distribution. Our simulations show that a number of electrostatic interactions appear to contribute to localization, including hydrogen bonding to the lipid carbonyl groups, cation-π interactions, interactions between the indole dipole and the lipid bilayer's strong interfacial electric field, and nonspecific electrostatic stabilization due to a mismatch in the variation of the nonpolar forces and local dielectric with position in the bilayer. PMID:16815896

  15. Reactions of a Ruthenium Complex with Substituted N-Propargyl Pyrroles.

    PubMed

    Chia, Pi-Yeh; Huang, Shou-Ling; Liu, Yi-Hong; Lin, Ying-Chih

    2016-04-05

    In an investigation into the chemical reactions of N-propargyl pyrroles 1 a-c, containing aldehyde, keto, and ester groups on the pyrrole ring, with [Ru]-Cl ([Ru]=Cp(PPh3 )2 Ru; Cp=C5 H5 ), an aldehyde group in the pyrrole ring is found to play a crucial role in stimulating the cyclization reaction. The reaction of 1 a, containing an aldehyde group, with [Ru]-Cl in the presence of NH4 PF6 yields the vinylidene complex 2 a, which further reacts with allyl amine to give the carbene complex 6 a with a pyrrolizine group. However, if 1 a is first reacted with allyl amine to yield the iminenyne 8 a, then the reaction of 8 a with [Ru]-Cl in the presence of NH4 PF6 yields the ruthenium complex 9 a, containing a cationic pyrrolopyrazinium group, which has been fully characterized by XRD analysis. These results can be adequately explained by coordination of the triple bond of the propargyl group to the ruthenium metal center first, followed by two processes, that is, formation of a vinylidene intermediate or direct nucleophilic attack. Additionally, the deprotonation of 2 a by R4 NOH yields the neutral acetylide complex 3 a. In the presence of NH4 PF6 , the attempted alkylation of 3 a resulted in the formation the Fischer-type amino-carbene complex 5 a as a result of the presence of NH3, which served as a nucleophile. With KPF6, the alkylation of 3 a with ethyl and benzyl bromoacetates afforded the disubstituted vinylidene complexes 10 a and 11 a, containing ester groups, which underwent deprotonation reactions to give the furyl complexes 12 a and 13 a, respectively. For 13 a, containing an O-benzyl group, subsequent 1,3-migration of the benzyl group was observed to yield product 14 a with a lactone unit. Similar reactivity was not observed for the corresponding N-propargyl pyrroles 1 b and 1 c, which contained keto and ester groups, respectively, on the pyrrole ring. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. NMR and EPR Studies of Chloroiron(III) Tetraphenylchlorin and Its Complexes with Imidazoles and Pyridines of Widely Differing Basicities

    PubMed Central

    Cai, Sheng; Shokhireva, Tatjana Kh.; Lichtenberger, Dennis L.; Walker, F. Ann

    2008-01-01

    The NMR and EPR spectra of two bis-imidazole and three bis-pyridine complexes of tetraphenylchlorinatoiron(III), [(TPC)Fe(L)2]+ (L = Im-d4, 2-MeHIm, 4-Me2NPy, Py and 4-CNPy) have been investigated. The full resonance assignments of the [(TPC)Fe(L)2]+ complexes of this study have been made from COSY and NOESY experiments and ADF calculations. Unlike the [(OEC)Fe(L)2]+ complexes reported previously (Cai, S.; Lichtenberger, D. L.; Walker, F. A. Inorg. Chem. 2005, 44, 1890-1903), the NMR data for the [(TPC)Fe(L)2]+ complexes of this study indicate that the ground state is S = ½ for each bis-ligand complex, whereas a higher spin state was present at NMR temperatures for the Py and 4-CNPy complexes of (OEC)Fe(III). The pyrrole-8,17 and pyrroline-H of all [TPCFe(L)2]+ show large magnitude chemical shifts (hence indicating large spin density on the adjacent carbons that are part of the π system), while pyrrole-12,13-CH2 and -7,18-CH2 protons show much smaller chemical shifts, as predicted by the spin densities obtained from ADF calculations. The magnitude of the chemical shifts decreases with decreasing donor ability of the substituted pyridine ligands, with the non-hindered imidazole ligand having slightly larger magnitude chemical shifts than the most basic pyridine, even though its basicity is significantly lower (4-Me2NPyH+ pKa = 9.7, H2Im+ pKa = 6.65 (adjusted for the statistical factor of 2 protons)). The temperature dependence of the chemical shifts of all but the 4-Me2NPy bis-ligand complexes studied over the temperature range of the NMR investigations shows that most of them have mixed (dxy)2(dxz,dyz)3/(dxzdyz)4(dxy)1 electron configurations that cannot be resolved by temperature-dependent fitting of the proton chemical shifts, with a S = 3/2 excited state in each case that in most cases lies at more than kT at room temperature above the ground state. The observed pattern of chemical shifts of the 4-CNPy complex and analysis of the temperature dependence

  17. Novel indole sulfides as potent HIV-1 NNRTIs.

    PubMed

    Brigg, Siobhan; Pribut, Nicole; Basson, Adriaan E; Avgenikos, Moscos; Venter, Reinhardt; Blackie, Margaret A; van Otterlo, Willem A L; Pelly, Stephen C

    2016-03-15

    In a previous communication we described a series of indole based NNRTIs which were potent inhibitors of HIV replication, both for the wild type and K103N strains of the virus. However, the methyl ether functionality on these compounds, which was crucial for potency, was susceptible to acid promoted indole assisted SN1 substitution. This particular problem did not bode well for an orally bioavailable drug. Here we describe bioisosteric replacement of this problematic functional group, leading to a series of compounds which are potent inhibitors of HIV replication, and are acid stable.

  18. Indole Alkaloids from the Leaves of Nauclea officinalis.

    PubMed

    Fan, Long; Liao, Cheng-Hui; Kang, Qiang-Rong; Zheng, Kai; Jiang, Ying-Chun; He, Zhen-Dan

    2016-07-23

    Three new indole alkaloids, named naucleamide G (1), and nauclealomide B and C (5 and 6), were isolated from the n-BuOH-soluble fraction of an EtOH extract of the leaves of Nauclea officinalis, together with three known alkaloids, paratunamide C (2), paratunamide D (3) and paratunamide A (4). The structures with absolute configurations of the new compounds were identified on the basis of 1D and 2D NMR, HRESIMS, acid hydrolysis and quantum chemical circular dichroism (CD) calculation. According to the structures of isolated indole alkaloids, their plausible biosynthetic pathway was deduced.

  19. New indole alkaloids from the bark of Alstonia scholaris.

    PubMed

    Salim, Angela A; Garson, Mary J; Craik, David J

    2004-09-01

    A new indole alkaloid, akuammiginone (1), and a new glycosidic indole alkaloid, echitamidine-N-oxide 19-O-beta-d-glucopyranoside (2), together with the five known alkaloids, echitaminic acid (3), echitamidine N-oxide (4), N(b)-demethylalstogustine N-oxide (5), akuammicine N-oxide (6), and N(b)-demethylalstogustine (7), were isolated from the trunk bark of Alstonia scholaris collected in Timor, Indonesia. The structures of all compounds were elucidated by spectroscopic methods. This is the first report of compounds 3-5and 7 in A. scholaris. Some NMR assignments of the known compounds were revised.

  20. Dibromidobis(pyridine-3-carbonitrile-κN)zinc(II).

    PubMed

    Ghiasi, Reza

    2010-12-18

    In the title compound, [ZnBr(2)(C(6)H(4)N(2))(2)], the Zn(II) atom is four coordinated in a slightly distorted tetra-hedral fashion by two pyridine N atoms and two Br(-) anions. π-π inter-actions between adjacent pyridine rings [centroid-centroid distance = 3.6229 (19) Å] are the main factor controlling the packing and are effective in the stabilization of the crystal structure.

  1. Metabolic Engineering in Nicotiana benthamiana Reveals Key Enzyme Functions in Arabidopsis Indole Glucosinolate Modification[W

    PubMed Central

    Pfalz, Marina; Mikkelsen, Michael Dalgaard; Bednarek, Paweł; Olsen, Carl Erik; Halkier, Barbara Ann; Kroymann, Juergen

    2011-01-01

    Indole glucosinolates, derived from the amino acid Trp, are plant secondary metabolites that mediate numerous biological interactions between cruciferous plants and their natural enemies, such as herbivorous insects, pathogens, and other pests. While the genes and enzymes involved in the Arabidopsis thaliana core biosynthetic pathway, leading to indol-3-yl-methyl glucosinolate (I3M), have been identified and characterized, the genes and gene products responsible for modification reactions of the indole ring are largely unknown. Here, we combine the analysis of Arabidopsis mutant lines with a bioengineering approach to clarify which genes are involved in the remaining biosynthetic steps in indole glucosinolate modification. We engineered the indole glucosinolate biosynthesis pathway into Nicotiana benthamiana, showing that it is possible to produce indole glucosinolates in a noncruciferous plant. Building upon this setup, we demonstrate that all members of a small gene subfamily of cytochrome P450 monooxygenases, CYP81Fs, are capable of carrying out hydroxylation reactions of the glucosinolate indole ring, leading from I3M to 4-hydroxy-indol-3-yl-methyl and/or 1-hydroxy-indol-3-yl-methyl glucosinolate intermediates, and that these hydroxy intermediates are converted to 4-methoxy-indol-3-yl-methyl and 1-methoxy-indol-3-yl-methyl glucosinolates by either of two family 2 O-methyltransferases, termed indole glucosinolate methyltransferase 1 (IGMT1) and IGMT2. PMID:21317374

  2. Role of Indole Production on Virulence of Vibrio cholerae Using Galleria mellonella Larvae Model.

    PubMed

    Nuidate, Taiyeebah; Tansila, Natta; Saengkerdsub, Suwat; Kongreung, Jetnaphang; Bakkiyaraj, Dhamodharan; Vuddhakul, Varaporn

    2016-09-01

    Cell to cell communication facilitated by chemical signals plays crucial roles in regulating various cellular functions in bacteria. Indole, one such signaling molecule has been demonstrated to control various bacterial phenotypes such as biofilm formation and virulence in diverse bacteria including Vibrio cholerae. The present study explores some key factors involved in indole production and the subsequent pathogenesis of V. cholerae. Indole production was higher at 37 °C than at 30 °C, although the growth at 37 °C was slightly higher. A positive correlation was observed between indole production and biofilm formation in V. cholerae. Maximum indole production was detected at pH 7. There was no significant difference in indole production between clinical and environmental V. cholerae isolates, although indole production in one environmental isolate was significantly different. Both growth and indole production showed relevant changes with differences in salinity. An indole negative mutant strain was constructed using transposon mutagenesis and the direct effect of indole on the virulence of V. cholerae was evaluated using Galleria mellonella larvae model. Comparison to the wild type strain, the mutant significantly reduced the mortality of G. mellonella larvae which regained its virulence after complementation with exogenous indole. A gene involved in indole production and the virulence of V. cholerae was identified.

  3. Cooperative catalysis by bovine serum albumin-iodine towards cascade oxidative coupling-C(sp(2))-H sulfenylation of indoles/hydroxyaryls with thiophenols on water.

    PubMed

    Saima; Equbal, Danish; Lavekar, Aditya G; Sinha, Arun K

    2016-06-22

    Cooperative cascade catalysis by bovine serum albumin (BSA)-iodine allows for the first time the performance of C(sp(2))-H sulfenylation of indole from readily available thiophenol (-SH bond) via in situ generation/cleavage of disulfide (S-S bond) in air under aqueous conditions, whereas BSA or I2 individually do not permit this two step sequence to occur in the same pot towards C-S bond formation. This green cooperative protocol is extendable to sulfenylation of hydroxyaryls (i.e. 2-naphthol or 4-hydroxycoumarin) with diverse thiols (aryl/heteroaryl) without using any toxic metal catalysts, bases or oxidants, thus rendering the process environmentally and economically reliable. Further, the gram scale synthesis of a COX-2 inhibitor (3-(pyridin-2-ylthio)-1H-indole), regioselectivity and recyclability (up to four cycles) are the additional merits of this cooperative cascade bio-chemocatalytic (BSA-I2) protocol. Moreover, HPLC and ESI-MS provide powerful insights into the mechanistic aspects of the above cascade sulfenylation reaction.

  4. Control of Breast Tumor Cell Growth by Dietary Indoles

    DTIC Science & Technology

    1997-09-01

    anticarcinogenesis by indole-3-carbinol: detailed in vivo DNA binding dose-response studies after dietary administration with aflatoxin B1 . Carcinogenesis 9, 427-430...lipofectamine (Gibco BRL) mixtures were prepared by mixing 1 Vg of ERE-vit-CAT reporter (-596 to +21 of the Xenopus laevis vitellogenin B1 genomic

  5. Selective indole-based ECE inhibitors: synthesis and pharmacological evaluation.

    PubMed

    Brands, Michael; Ergüden, Jens-Kerim; Hashimoto, Kentaro; Heimbach, Dirk; Krahn, Thomas; Schröder, Christian; Siegel, Stephan; Stasch, Johannes-Peter; Tsujishita, Hideki; Weigand, Stefan; Yoshida, Nagahiro H

    2006-01-01

    Inhibition of the metalloprotease ECE-1 may be beneficial for the treatment of coronary heart disease, cancer, renal failure, and urological disorders. A novel class of indole-based ECE inhibitors was identified by high throughput screening. Optimization of the original screening lead structure 6 led to highly potent inhibitors such as 11, which bears a bisaryl amide moiety linked to the indole C2 position through an amide group. Docking of 11 into a model structure of ECE revealed a unique binding mode in which the Zn center of the enzyme is not directly addressed by the inhibitor, but key interactions are suggested for the central amide group. Testing of the lead compound 6 in hypertensive Dahl S rats resulted in a decrease in blood pressure after an initial period in which the blood pressure remained unchanged, most probably the result of ET-1 already present. Indole derivative 6 also displays a cardio-protective effect in a mouse model of acute myocardial infarction after oral administration. The more potent chloropyridine derivative 9 antagonizes big-ET-1-induced increase in blood pressure in rats at intravenous administration of 3 mg kg-1. All ECE inhibitors of the indole class showed high selectivity for ECE over related metalloproteases such as NEP and ACE. Therefore, these compounds might have further potential as drugs for the treatment of coronary heart diseases.

  6. Indole alkaloids from the seeds of Centaurea cyanus (Asteraceae).

    PubMed

    Sarker, S D; Laird, A; Nahar, L; Kumarasamy, Y; Jaspars, M

    2001-08-01

    Preparative RP-HPLC analysis of a methanol extract of the seeds of Centaurea cyanus afforded four indole alkaloids: moschamine, cis-moschamine, centcyamine and cis-centcyamine, the latter two being new natural products. Structures of these compounds were elucidated by comprehensive spectroscopic analyses. General toxicity of the isolates was determined by Brine Shrimp Lethality bioassay.

  7. Organocatalytic enantioselective indole alkylations of alpha,beta-unsaturated ketones.

    PubMed

    Chen, Wei; Du, Wei; Yue, Lei; Li, Rui; Wu, Yong; Ding, Li-Sheng; Chen, Ying-Chun

    2007-03-07

    The C3-selective enantioselective Michael-type Friedel-Crafts alkylations of indoles with nonchelating alpha,beta-unsaturated alkyl ketones, catalysed by a chiral primary amine derived from natural cinchonine, were investigated. The reactions, in the presence of 30 mol% catalyst, were smoothly conducted at 0 to -20 degrees C. Moderate to good ee (47-89%) has been achieved.

  8. Palladium-catalyzed direct arylation of indoles with arylsulfonyl hydrazides.

    PubMed

    Liu, Congrong; Ding, Lianghui; Guo, Guang; Liu, Weiwei; Yang, Fu-Lai

    2016-03-14

    A novel method to synthesise 2-arylindoles is demonstrated via direct arylation of indoles with arylsulfonyl hydrazides. Under the optimized reaction conditions, the reaction well tolerates a wide variety of functional groups to afford structurally diverse 2-arylindoles in good to excellent yields at 70 °C.

  9. Palladium-catalyzed direct arylation of indoles with cyclohexanones.

    PubMed

    Chen, Shanping; Liao, Yunfeng; Zhao, Feng; Qi, Hongrui; Liu, Saiwen; Deng, Guo-Jun

    2014-03-21

    A novel palladium catalyzed approach to 3-arylindoles was developed from indoles and cyclohexanones. Various cyclohexanones acted as aryl sources via an alkylation and dehydrogenation sequence using molecular oxygen as the hydrogen acceptor. This method showed good regioselectivity and afforded 3-arylindoles as the sole products.

  10. New indole alkaloids from the roots of Ochrosia acuminata.

    PubMed

    Salim, Angela A; Garson, Mary J; Craik, David J

    2004-10-01

    Two new indole alkaloids, polyneuridine-N-oxide (1) and 17-hydroxy-10-methoxy-yohimbane (2), together with seven known alkaloids were isolated from the roots of Ochrosia acuminata collected in Savu, Indonesia. 9-Methoxyellipticine (3) and ellipticine (4) were responsible for the antitumor activities of the extract. The structures of all compounds were elucidated using MS and NMR methods.

  11. Tenualexin, other phytoalexins and indole glucosinolates from wild cruciferous species.

    PubMed

    Pedras, M Soledade C; Yaya, Estifanos E

    2014-06-01

    In general, the chemodiversity of phytoalexins, elicited metabolites involved in plant defense mechanisms against microbial pathogens, correlates with the biodiversity of their sources. In this work, the phytoalexins produced by four wild cruciferous species (Brassica tournefortii, Crambe abyssinica (crambe), Diplotaxis tenuifolia (sand rocket), and Diplotaxis tenuisiliqua (wall rocket)) were identified and quantified by HPLC with photodioarray and electrospray mass detectors. In addition, the production of indole glucosinolates, biosynthetic precursors of cruciferous phytoalexins, was evaluated. Tenualexin, (=2-(1,4-dimethoxy-1H-indol-3-yl)acetonitrile), the first cruciferous phytoalexin containing two MeO substituents in the indole ring, was isolated from D. tenuisiliqua, synthesized, and evaluated for antifungal activity. The phytoalexins cyclobrassinin and spirobrassinin were detected in B. tournefortii and C. abyssinica, whereas rutalexin and 4-methoxybrassinin were only found in B. tournefortii. D. tenuifolia, and D. tenuisiliqua produced 2-(1H-indol-3-yl)acetonitriles as phytoalexins. Because tenualexin appears to be one of the broad-range antifungals occurring in crucifers, it is suggested that D. tenuisiliqua may have disease resistance traits important to be incorporated in commercial breeding programs.

  12. Diastereoselective Synthesis of Biologically Active Cyclopenta[b]indoles.

    PubMed

    Santos, Marilia S; Fernandes, Daniara C; Rodrigues, Manoel T; Regiani, Thais; Andricopulo, Adriano D; Ruiz, Ana Lúcia T G; Vendramini-Costa, Débora B; de Carvalho, João E; Eberlin, Marcos N; Coelho, Fernando

    2016-08-05

    The cyclopenta[b]indole motif is present in several natural and synthetic biologically active compounds, being directly responsible for the biological effects some of them present. We described herein a three step sequence for the synthesis of cyclopenta[b]indoles with a great structural diversity. The method is based on an oxidative Michael addition of suitable indoles on the double bond of Morita-Baylis-Hillman adducts mediated by a hypervalent iodine reagent (IBX) to form β-ketoesters, which were chemoselectively reduced with NaBH4 in THF to give the corresponding β-hydroxy-esters. The diastereoisomeric mixture was then treated with a catalytic amount of triflic acid (20 mol %) to give cyclopenta[b]indoles with overall yields ranging from 8 to 73% (for 2 steps). The acid-catalyzed cyclization step gave the required heterocycles, via an intramolecular Friedel-Crafts reaction, with high diastereoselectivity, where only the trans product was observed. A mechanistic study monitored by ESI-(+)-MS was also conducted to collect evidence about the mechanism of this reaction. The new molecules herein synthesized were also evaluated against a panel of human cancer cells demonstrating a promising antitumoral profile.

  13. Monoterpenoid indole alkaloids from the bark of Alstonia scholaris.

    PubMed

    Feng, Tao; Cai, Xiang-Hai; Zhao, Pei-Ji; Du, Zhi-Zhi; Li, Wei-Qi; Luo, Xiao-Dong

    2009-11-01

    Six new monoterpenoid indole alkaloids, scholarisines B-G (1- 6), together with 15 known analogues (7- 21), were isolated from the bark of Alstonia scholaris. Their structures were determined by 1D and 2D NMR spectra and MS analyses. The structure of 1 was further supported by the single-crystal X-ray. Georg Thieme Verlag KG Stuttgart, New York.

  14. Indole: An evolutionarily conserved influencer of behavior across kingdoms

    USDA-ARS?s Scientific Manuscript database

    Indole, which is produced from the breakdown of the essential amino acid tryptophan, is a key environmental cue that is used by many organisms. But why is its use so ubiquitous, and how does it function to modulate interactions among such diverse organisms? Here, we review the literature to addres...

  15. Photolysis of Indole-Containing Mycotoxins to Fluorescent Products

    USDA-ARS?s Scientific Manuscript database

    Photochemical reaction of the non-fluorescent mycotoxin cyclopiazonic acid (CPA) to fluorescent products was recently reported. Because CPA contains an indole moiety, believed to contribute to the fluorescence, it was of interest to determine whether the effect might be more generally applicable to ...

  16. Aniline is an inducer, and not a precursor, for indole derivatives in Rubrivivax benzoatilyticus JA2.

    PubMed

    Mujahid, Mohammed; Sasikala, Ch; Ramana, Ch V

    2014-01-01

    Rubrivivax benzoatilyticus JA2 and other anoxygenic photosynthetic bacteria produce indole derivatives when exposed to aniline, a xenobiotic compound. Though this phenomenon has been reported previously, the role of aniline in the production of indoles is still a biochemical riddle. The present study aims at understanding the specific role of aniline (as precursor or stimulator) in the production of indoles and elucidating the biochemical pathway of indoles in aniline-exposed cells by using stable isotope approaches. Metabolic profiling revealed tryptophan accumulation only in aniline exposed cells along with indole 3-acetic acid (IAA) and indole 3-aldehyde (IAld), the two major catabolites of tryptophan. Deuterium labelled aniline feeding studies revealed that aniline is not a precursor of indoles in strain JA2. Further, production of indoles only in aniline-exposed cells suggests that aniline is an indoles stimulator. In addition, production of indoles depended on the presence of a carbon source, and production enhanced when carbon sources were added to the culture. Isotope labelled fumarate feeding identified, fumarate as the precursor of indole, indicating de novo synthesis of indoles. Glyphosate (shikimate pathway inhibitor) inhibited the indoles production, accumulation of tryptophan, IAA and IAld indicating that indoles synthesis in strain JA2 occurs via the de novo shikimate pathway. The up-regulation of anthranilate synthase gene and induction of anthranilate synthase activity correlated well with tryptophan production in strain JA2. Induction of tryptophan aminotransferase and tryptophan 2-monooxygenase activities corroborated well with IAA levels, suggesting that tryptophan catabolism occurs simultaneously in aniline exposed cells. Our study demonstrates that aniline (stress) stimulates tryptophan/indoles synthesis via the shikimate pathway by possibly modulating the metabolic pathway.

  17. Aniline Is an Inducer, and Not a Precursor, for Indole Derivatives in Rubrivivax benzoatilyticus JA2

    PubMed Central

    Mohammed, Mujahid; Ch, Sasikala; Ch, Ramana V.

    2014-01-01

    Rubrivivax benzoatilyticus JA2 and other anoxygenic photosynthetic bacteria produce indole derivatives when exposed to aniline, a xenobiotic compound. Though this phenomenon has been reported previously, the role of aniline in the production of indoles is still a biochemical riddle. The present study aims at understanding the specific role of aniline (as precursor or stimulator) in the production of indoles and elucidating the biochemical pathway of indoles in aniline-exposed cells by using stable isotope approaches. Metabolic profiling revealed tryptophan accumulation only in aniline exposed cells along with indole 3-acetic acid (IAA) and indole 3-aldehyde (IAld), the two major catabolites of tryptophan. Deuterium labelled aniline feeding studies revealed that aniline is not a precursor of indoles in strain JA2. Further, production of indoles only in aniline-exposed cells suggests that aniline is an indoles stimulator. In addition, production of indoles depended on the presence of a carbon source, and production enhanced when carbon sources were added to the culture. Isotope labelled fumarate feeding identified, fumarate as the precursor of indole, indicating de novo synthesis of indoles. Glyphosate (shikimate pathway inhibitor) inhibited the indoles production, accumulation of tryptophan, IAA and IAld indicating that indoles synthesis in strain JA2 occurs via the de novo shikimate pathway. The up-regulation of anthranilate synthase gene and induction of anthranilate synthase activity correlated well with tryptophan production in strain JA2. Induction of tryptophan aminotransferase and tryptophan 2-monooxygenase activities corroborated well with IAA levels, suggesting that tryptophan catabolism occurs simultaneously in aniline exposed cells. Our study demonstrates that aniline (stress) stimulates tryptophan/indoles synthesis via the shikimate pathway by possibly modulating the metabolic pathway. PMID:24533057

  18. Microbial degradation of pyridine using Pseudomonas sp. and isolation of plasmid responsible for degradation.

    PubMed

    Mohan, S Venkata; Sistla, Srinivas; Guru, R Kumar; Prasad, K Krishna; Kumar, C Suresh; Ramakrishna, S V; Sarma, P N

    2003-01-01

    Pseudomonas (PI2) capable of degrading pyridine was isolated from the mixed population of the activated sludge unit which was being used for treating complex effluents, the strain was characterized. Aerobic degradation of pyridine was studied with the isolated strain and the growth parameters were evaluated. Pyridine degradation was further conformed by chromatography (HPLC) analysis. The process parameters like biomass growth and dissolved oxygen consumption were monitored during pyridine degradation. In order to conform with the plasmid capability to degrade pyridine, the requisite plasmid was isolated and transferred to DH 5alpha Escherichia coli. The subsequent biodegradation studies revealed the ability of the transformed plasmid capability to degrade the pyridine.

  19. Pyridine nucleotide redox abnormalities in diabetes.

    PubMed

    Ido, Yasuo

    2007-07-01

    In addition to hyperglycemia, diabetes is associated with increased levels of circulating free fatty acids, lactate, and branched chain amino acids, all of which produce an excessive reduced form of pyridine nucleotides NADH (reductive stress) in the cytosol and mitochondria. Our studies suggest that cytosolic NADH reductive stress under high glucose is largely caused by increased flux of glucose through polyol (sorbitol) pathway consisting of aldose reductase and sorbitol dehydrogenase. Inhibition of aldose reductase that blocks the polyol pathway has been shown to ameliorate diabetic neuropathy in humans. Cytosolic NADH reductive stress is predicted to increase production of diglycerides, reactive oxygen species, and methylglyoxal. Recent studies indicate that increasing NADH affects gene expression through the NADH activating transcriptional co-repressor, C-terminal binding protein (CtBP). In addition, it has been shown that the NADH utilizing enzyme, glyceraldehyde-3-phosphate dehydrogenase, participates as transcriptional regulator. These findings testify to the importance of NADH redox balance in cell biology and pathogenesis of diabetes and its complications. For example, through CtBP, the high NADH to NAD(+) ratio decreases an expression of SirT1, the protein inducing longevity and anti-apoptosis. This review covers metabolic cascades causing reductive stress and oxidative stress in diabetes after a brief introduction of the redox concept.

  20. Cascade multicomponent synthesis of indoles, pyrazoles, and pyridazinones by functionalization of alkenes.

    PubMed

    Matcha, Kiran; Antonchick, Andrey P

    2014-10-27

    The development of multicomponent reactions for indole synthesis is demanding and has hardly been explored. The present study describes the development of a novel multicomponent, cascade approach for indole synthesis. Various substituted indole derivatives were obtained from simple reagents, such as unfunctionalized alkenes, diazonium salts, and sodium triflinate, by using an established straightforward and regioselective method. The method is based on the radical trifluoromethylation of alkenes as an entry into Fischer indole synthesis. Besides indole synthesis, the application of the multicomponent cascade reaction to the synthesis of pyrazoles and pyridazinones is described. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. Simultaneous detection and quantification of indole-3-acetic acid (IAA) and indole-3-butyric acid (IBA) produced by rhizobacteria from l-tryptophan (Trp) using HPTLC.

    PubMed

    Goswami, Dweipayan; Thakker, Janki N; Dhandhukia, Pinakin C

    2015-03-01

    A simple, quick and reliable method is proposed for the detection and quantitation of indole-3-acetate (IAA) and indole-3-butyrate (IBA), an auxin phytohormone produced by rhizobacteria from l-tryptophan (Trp) metabolism using high performance thin-layer chromatography (HPTLC). Microbial auxin biosynthesis routes involve Trp as a precursor where other than IAA and IBA, products such as indole-3-pyruvate (IPA), indole-3-acetamide (IAM), tryptamine, indole-3-acetonitrile (IAN), indole-3-lactic acid (ILA) and indole-3-acetaldehyde (IAAld) are also produced. In traditional spectrophotometric method, Salkowski reagent develops color by reacting with indolic compounds. The color development is non-specific contributed by several Trp derivatives produced by rhizobacteria rather than IAA only. To overcome this limitation, HPTLC based protocol is developed to precisely detect and quantify IAA and IBA in the range of 100 to 1000ng per spot. This protocol is applicable to detect and quantify IAA and IBA from microbial samples ignoring other Trp derivatives. For microbial samples, the spectrophotometric method gives larger values as compared to HPTLC derived values which may be attributed by total indolic compounds reacting with Salkowski reagent rather than only IAA and/or IBA. Copyright © 2015 Elsevier B.V. All rights reserved.

  2. Regio- and chemoselective N-1 acylation of indoles: Pd-catalyzed domino cyclization to afford 1,2-fused tricyclic indole scaffolds.

    PubMed

    Liu, Yongxian; Huang, Yuanqiong; Song, Hongjian; Liu, Yuxiu; Wang, Qingmin

    2015-03-27

    A concise method for the synthesis of 1,2-fused tricyclic indole scaffolds by domino cyclization involving a Pd-catalyzed Sonogashira coupling, indole cyclization, regio- and chemoselective N-1 acylation, and 1,4-Michael addition is reported. This method provides straightforward access to tetrahydro[1,4]diazepino[1,2-a]indole and hexahydro[1,5]diazocino[1,2-a]indole scaffolds. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. Role of the ribose-specific marker furfuryl-amine in the formation of aroma active 1-(furan-2-ylmethyl)-1H-pyrrole (or furfuryl-pyrrole) derivatives.

    PubMed

    Nikolov, Plamen Y; Yaylayan, Varoujan A

    2012-10-10

    Furfuryl-pyrroles possess a diverse range of organoleptic properties described as roasted, chocolaty, green, horseradish-like, and mushroom-like and are detected in various foods such as coffee, chocolate, popcorn, and roasted chicken. Although their origin in food was attributed to furfuryl-amine, the latter has not been detected so far in Maillard model systems or in foods. In this study, furfuryl-amine was shown to be formed specifically from ribose through nitrogen atom transfer from the α-amino group of any amino acid. Such a transfer can be achieved through decarboxylation of the Schiff base adduct and isomerization followed by hydrolysis. Through the use of (15)Nα-lysine it was revealed that only the (15)Nα nitrogen atom was incorporated into its structure, indicating a specific role for the carboxylate moiety in the mechanism of its formation. Furthermore, isotope labeling studies have indicated that furfuryl-pyrrole derivatives can be formed by the interaction of 2 mol of furfuryl-amine with 3-deoxyribosone followed by dehydration and cyclization to form 1-(furan-2-yl)-N-{[1-(furan-2-ylmethyl)-1H-pyrrol-2-yl]methylidene}methanamine. After hydrolysis, this intermediate can generate furfuryl-formyl-pyrrole, furfuryl-pyrrole carboxylic acid, and furfuryl-pyrrole. In this study, the furfuryl-amine derivatives were also detected in different coffee beans after pyrolysis and analysis by GC-MS. The potential of these compounds to form in aqueous model systems at a temperature of 120 °C was also demonstrated.

  4. Pyrrole Derivatives and Diterpene Alkaloids from the South China Sea Sponge Agelas nakamurai.

    PubMed

    Chu, Mei-Jun; Tang, Xu-Li; Qin, Guo-Fei; Sun, Yan-Ting; Li, Lei; de Voogd, Nicole J; Li, Ping-Lin; Li, Guo-Qiang

    2017-02-21

    Two pairs of new non-brominated racematic pyrrole derivatives, (±)-nakamurine D (1) and (±)-nakamurine E (2), two new diterpene alkaloids, iso-agelasine C (16), and iso-agelasidine B (21), together with fifteen known pyrrole derivatives((±)-3 - 15), five known diterpene alkaloids (17 - 20, 22) were isolated from the South China Sea sponge Agelas nakamurai. The racemic mixtures, compounds 1 - 4, were resolved into four pairs of enantiomers, (+)-1 and (-)-1, (+)-2 and (-)-2, (+)-3 and (-)-3, and (+)-4 and (-)-4, by chiral HPLC. The structures and absolute configurations were elucidated on the basis of comprehensive spectroscopic analyses, quantum chemical calculations, quantitative measurements of molar rotations, application of van't Hoff's principle of optical superposition, and comparison with the literature data. The NMR and MS data of compound 3 are reported for the first time, as the structure was listed in SciFinder Scholar with no associated reference. These non-brominated pyrrole derivatives were found in this species for the first time. Compound 18 showed valuable cytotoxicities against HL-60, K562, and HCT-116 cell lines with IC50 values of 12.4, 16.0, and 19.8 μM, respectively. Compounds 16 - 19, 21, and 22 showed potent antifungal activities against Candida albicans with MIC values ranging from 0.59 to 4.69 μg/mL. Compounds 16 - 19 exhibited moderate antibacterial activities against Proteusbacillus vulgaris (MIC values ranging from 9.38 to 18.75 μg/mL). This article is protected by copyright. All rights reserved.

  5. Formation of Volatile Tea Constituent Indole During the Oolong Tea Manufacturing Process.

    PubMed

    Zeng, Lanting; Zhou, Ying; Gui, Jiadong; Fu, Xiumin; Mei, Xin; Zhen, Yunpeng; Ye, Tingxiang; Du, Bing; Dong, Fang; Watanabe, Naoharu; Yang, Ziyin

    2016-06-22

    Indole is a characteristic volatile constituent in oolong tea. Our previous study indicated that indole was mostly accumulated at the turn over stage of oolong tea manufacturing process. However, formation of indole in tea leaves remains unknown. In this study, one tryptophan synthase α-subunit (TSA) and three tryptophan synthase β-subunits (TSBs) from tea leaves were isolated, cloned, sequenced, and functionally characterized. Combination of CsTSA and CsTSB2 recombinant protein produced in Escherichia coli exhibited the ability of transformation from indole-3-glycerol phosphate to indole. CsTSB2 was highly expressed during the turn over process of oolong tea. Continuous mechanical damage, simulating the turn over process, significantly enhanced the expression level of CsTSB2 and amount of indole. These suggested that accumulation of indole in oolong tea was due to the activation of CsTSB2 by continuous wounding stress from the turn over process. Black teas contain much less indole, although wounding stress is also involved in the manufacturing process. Stable isotope labeling indicated that tea leaf cell disruption from the rolling process of black tea did not lead to the conversion of indole, but terminated the synthesis of indole. Our study provided evidence concerning formation of indole in tea leaves for the first time.

  6. Systematic investigation and microbial community profile of indole degradation processes in two aerobic activated sludge systems

    PubMed Central

    Ma, Qiao; Qu, Yuanyuan; Zhang, Xuwang; Liu, Ziyan; Li, Huijie; Zhang, Zhaojing; Wang, Jingwei; Shen, Wenli; Zhou, Jiti

    2015-01-01

    Indole is widely spread in various environmental matrices. Indole degradation by bacteria has been reported previously, whereas its degradation processes driven by aerobic microbial community were as-yet unexplored. Herein, eight sequencing batch bioreactors fed with municipal and coking activated sludges were constructed for aerobic treatment of indole. The whole operation processes contained three stages, i.e. stage I, glucose and indole as carbon sources; stage II, indole as carbon source; and stage III, indole as carbon and nitrogen source. Indole could be completely removed in both systems. Illumina sequencing revealed that alpha diversity was reduced after indole treatment and microbial communities were significantly distinct among the three stages. At genus level, Azorcus and Thauera were dominant species in stage I in both systems, while Alcaligenes, Comamonas and Pseudomonas were the core genera in stage II and III in municipal sludge system, Alcaligenes and Burkholderia in coking sludge system. In addition, four strains belonged to genera Comamonas, Burkholderia and Xenophilus were isolated using indole as sole carbon source. Burkholderia sp. IDO3 could remove 100 mg/L indole completely within 14 h, the highest degradation rate to date. These findings provide novel information and enrich our understanding of indole aerobic degradation processes. PMID:26657581

  7. Isolation of Indole Utilizing Bacteria Arthrobacter sp. and Alcaligenes sp. From Livestock Waste.

    PubMed

    Kim, Minsu; Lee, Jin-Hyung; Kim, Eonmi; Choi, Hyukjae; Kim, Younghoon; Lee, Jintae

    2016-06-01

    Indole is an interspecies and interkingdom signaling molecule widespread in different environmental compartment. Although multifaceted roles of indole in different biological systems have been established, little information is available on the microbial utilization of indole in the context of combating odor emissions from different types of waste. The present study was aimed at identifying novel bacteria capable of utilizing indole as the sole carbon and energy source. From the selective enrichment of swine waste and cattle feces, we identified Gram-positive and Gram-negative bacteria belonging to the genera Arthrobacter and Alcaligenes. Bacteria belonging to the genus Alcaligenes showed higher rates of indole utilization than Arthrobacter. Indole at 1.0 mM for growth was completely utilized by Alcaligenes sp. in 16 h. Both strains produced two intermediates, anthranilic acid and isatin, during aerobic indole metabolism. These isolates were also able to grow on several indole derivatives. Interestingly, an adaptive response in terms of a decrease in cell size was observed in both strains in the presence of indole. The present study will help to explain the degradation of indole by different bacteria and also the pathways through which it is catabolized. Furthermore, these novel bacterial isolates could be potentially useful for the in situ attenuation of odorant indole and its derivatives emitted from different types of livestock waste.

  8. Novel Microtubule-Interacting Phenoxy Pyridine and Phenyl Sulfanyl Pyridine Analogues for Cancer Therapy

    PubMed Central

    Anchoori, Ravi Kumar; Kortenhorst, Madeleine Susanne Quirine; Hidalgo, Manuel; Sarkar, Taradas; Hallur, Gurulingappa; Bai, Ruoli; Van Diest, Paul J.; Hamel, Ernest; Khan, Saeed R.

    2008-01-01

    Current microtubule inhibitory agents used in the clinic to treat cancer have severe side effects, and development of resistance is frequent. We have evaluated the antitumor effect of a novel 30-compound library of phenoxy pyridine and phenyl sulfanyl pyridine derivatives. MTT assays revealed that, of all 30 compounds tested, compounds 2 and 3 showed the largest decrease in proliferation (low μM range) against Panc1 and HS766T human pancreatic cancer cells. Flow cytometry experiments with MCF7 breast cancer cells showed a G2/M arrest comparable to that of colcemid. Immunofluorescence staining demonstrated complete disappearance of intracellular microtubules. Tubulin assembly assays, however, showed a dose-dependent decrease in tubulin assembly with compound 3 that seemed limited to about 50% of the control reaction. With compound 2 treatment, there was only a delay in the onset of assembly, with no effect on the extent of the reaction. Taken together, our results show that these novel microtubule inhibitors have promising anticancer activity and can be potentially used to overcome paclitaxel resistance in the clinical setting. PMID:18778046

  9. Indoles as therapeutics of interest in medicinal chemistry: Bird's eye view.

    PubMed

    Chadha, Navriti; Silakari, Om

    2017-07-07

    Indoles constitute extensively explored heterocyclic ring systems with wide range of applications in pathophysiological conditions that is, cancer, microbial and viral infections, inflammation, depression, migraine, emesis, hypertension, etc. Presence of indole nucleus in amino acid tryptophan makes it prominent in phytoconstituents such as perfumes, neurotransmitters, auxins (plant hormones), indole alkaloids etc. The interesting molecular architecture of indole makes them suitable candidates for the drug development. This review article provides an overview of the chemistry, biology, and toxicology of indoles focusing on their application as drugs. Our effort is to corroborate the information available on the natural indole alkaloids, indole based FDA approved drugs and clinical trial candidates having diverse therapeutic implementations. This compiled information may serve as a benchmark for the alteration of existing ligands to design novel potent molecules with lesser side effects. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  10. Copper-catalyzed C(sp(3))-H functionalization of ketones with vinyl azides: synthesis of substituted-1H-pyrroles.

    PubMed

    Donthiri, Ramachandra Reddy; Samanta, Supravat; Adimurthy, Subbarayappa

    2015-10-28

    Copper-catalyzed C(sp(3))-H functionalization of ketones with vinyl azides for the synthesis of substituted pyrroles has been developed. The method is a straightforward and efficient way to access a series of 2,3,5-trisubstituted-1H-pyrroles in modest to excellent yields with broad functional group tolerance under mild conditions.

  11. The Chemical and Physical Properties of Pyrrole-Based Conducting Polymers: The Characterization of As-Grown Films by X-Ray Photoemission Spectroscopy.

    DTIC Science & Technology

    1983-04-07

    by identifying the existence of both, pyrrole rinp and perchlorate anions. It should be mentioned, however, that no significant density of states can...XPS indicates one tetrafluoroborate anion for 4 pyrrole rinp in PP+BF . More precisely, 0.26 boron atoms were found on an average over 4 samples

  12. Lipid-lowering effects of ethyl 2-phenacyl-3-aryl-1H-pyrrole- 4-carboxylates in rodents.

    PubMed

    Holub, Justin M; O'Toole-Colin, Kathy; Getzel, Adam; Argenti, Anthony; Evans, Michael A; Smith, Daniel C; Dalglish, Gerard A; Rifat, Shahzad; Wilson, Donna L; Taylor, Brett M; Miott, Ulander; Glersaye, Josephine; Lam, Kam Suet; McCranor, Bryan J; Berkowitz, Joshua D; Miller, Robert B; Lukens, John R; Krumpe, Keith; Gupton, John T; Burnham, Bruce S

    2004-02-28

    A series of substituted 2-phenacyl-3-phenyl-1H-pyrrole-4-carboxylates were prepared from substituted acetophenones in 6 steps. The final condensations between a chloroenal and an aminoketone were carried out under neutral conditions in parallel to yield the series listed below. Selected pyrrole derivatives proved to be potent hypolipidemic agents lowering serum triglyceride concentrations in CF-1 male mice after 14 days of I.P. administration. One agent orally lowered serum cholesterol in Sprague-Dawley male rats at 2mg/kg/day after 14 days. The agents demonstrated a lowering of mouse serum LDL- cholesterol levels and selected compounds showed an elevation of serum HDL-cholesterol levels. The cholesterol concentrations in the liver were raised while the cholesterol and triglyceride contents of the aorta were significantly lowered by the selected trisubstituted pyrrole.

  13. Pyrrole- and dihydropyrrole-fused neonicotinoids: design, synthesis, and insecticidal evaluation.

    PubMed

    Ye, Zhenjun; Shi, Lina; Shao, Xusheng; Xu, Xiaoyong; Xu, Zhiping; Li, Zhong

    2013-01-16

    Versatile pyrrole- and dihydropyrrole-fused neonicotinoids were obtained from cyclic and non-cyclic nitroeneamines. Anhydrous aluminum chloride (AlCl₃) exhibited high catalytic selectivity for the synthesis of the titled etherified compounds at room temperature and the eliminated products under reflux conditions. The target molecules have been identified on the basis of satisfactory analytical and spectral [¹H and ¹³C nuclear magnetic resonance (NMR), high-resolution mass spectrometry (HRMS), and X-ray] data. All synthesized compounds have been screened for insecticidal activity. The preliminary insecticidal activity results showed that some of the aimed compounds displayed excellent insecticidal activity against cowpea aphids (Aphis craccivora).

  14. Capping the calix: How toluene completes cesium(i) coordination with calix[4]pyrrole

    DOE PAGES

    Ellis, Ross J.; Reinhart, Benjamin; Williams, Neil J.; ...

    2017-05-04

    The role of solvent in molecular recognition systems is under-researched and often ignored, especially when the solvent is considered “non-interacting”. This study concerns the role of toluene solvent in cesium(I) recognition by calix[4]pyrrole. We show that π-donor interactions bind toluene molecules onto the open face of the cation-receptor complex, thus “capping the calix.” As a result, by characterizing this unusual aromatically-saturated complex, we show how “non-interacting” aromatic solvents can directly coordinate receptor-bound cations and thus influence recognition.

  15. Copper-diamine-catalyzed N-arylation of pyrroles, pyrazoles, indazoles, imidazoles, and triazoles.

    PubMed

    Antilla, Jon C; Baskin, Jeremy M; Barder, Timothy E; Buchwald, Stephen L

    2004-08-20

    This paper details the copper-catalyzed N-arylation of pi-excessive nitrogen heterocycles. The coupling of either aryl iodides or aryl bromides with common nitrogen heterocycles (pyrroles, pyrazoles, indazoles, imidazoles, and triazoles) was successfully performed in good yield with catalysts derived from diamine ligands and CuI. General conditions were found that tolerate functional groups such as aldehydes, ketones, alcohols, primary amines, and nitriles on the aryl halide or heterocycle. Hindered aryl halides or heterocycles were also found to be suitable substrates using the conditions reported herein. Copyright 2004 American Chemical Society

  16. A rapid and specific method for the detection of indole in complex biological samples.

    PubMed

    Darkoh, Charles; Chappell, Cynthia; Gonzales, Christopher; Okhuysen, Pablo

    2015-12-01

    Indole, a bacterial product of tryptophan degradation, has a variety of important applications in the pharmaceutical industry and is a biomarker in biological and clinical specimens. Yet, specific assays to quantitate indole are complex and require expensive equipment and a high level of training. Thus, indole in biological samples is often estimated using the simple and rapid Kovács assay, which nonspecifically detects a variety of commonly occurring indole analogs. We demonstrate here a sensitive, specific, and rapid method for measuring indole in complex biological samples using a specific reaction between unsubstituted indole and hydroxylamine. We compared the hydroxylamine-based indole assay (HIA) to the Kovács assay and confirmed that the two assays are capable of detecting microgram amounts of indole. However, the HIA is specific to indole and does not detect other naturally occurring indole analogs. We further demonstrated the utility of the HIA in measuring indole levels in clinically relevant biological materials, such as fecal samples and bacterial cultures. Mean and median fecal indole concentrations from 53 healthy adults were 2.59 mM and 2.73 mM, respectively, but varied widely (0.30 mM to 6.64 mM) among individuals. We also determined that enterotoxigenic Escherichia coli strain H10407 produces 3.3 ± 0.22 mM indole during a 24-h period in the presence of 5 mM tryptophan. The sensitive and specific HIA should be of value in a variety of settings, such as the evaluation of various clinical samples and the study of indole-producing bacterial species in the gut microbiota. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  17. [Bioaugmented removal of pyridine and the microbial community dynamic analysis].

    PubMed

    Qiao, Lin; Zhao, Hong; Wang, Jian-Long

    2012-06-01

    The bioaugmented removal of pyridine was investigated through introducing immobilized Paracoccus sp. strain KT-5 capable of degrading pyridine into the lab-scale sequencing batch reactor (SBR) inoculated with activated sludge. The terminal restriction fragment length polymorphisms (T-RFLP) was used to analyzed the microbial community dynamics of two reactors during the whole operation process. The experimental results indicated that the introduction of immobilized strain KT-5 into the SBR could speed up the start-up of reactor, compared to the non-bioaugmented SBR. When the initial concentration of pyridine varied from 195.6 mg x L(-1) to 586.8 mg x L(-1), the bioaugmented effect was not significant; however, when the initial concentration of pyridine was 782.4-2934 mg x L(-1), the bioaugmentation role in pyridine degradation was obvious. The analysis of T-RFLP indicated that the introduced immobilized strain KT-5, as a dominant strain, always existed in both free and immobilized biomass of the bioaugmented SBR.

  18. Halogen Bonding in Iodo-perfluoroalkane/Pyridine Mixtures

    NASA Astrophysics Data System (ADS)

    Fan, Haiyan; Eliason, Jeffrey K.; Moliva A., C. Diane; Olson, Jason L.; Flancher, Scott M.; Gealy, M. W.; Ulness, Darin J.

    2009-12-01

    Mole fraction and temperature studies of halogen bonding between 1-iodo-perfluorobutane, 1-iodo-perfluorohexane, or 2-iodo-perfluoropropane and pyridine were performed using noisy light-based coherent anti-Stokes Raman scattering (I(2) CARS) spectroscopy. The ring breathing mode of pyridine both is highly sensitive to halogen bonding and provides a strong I(2) CARS signal. As the lone pair electrons from the pyridinyl nitrogen interact with the σ-hole on the iodine from the iodo-perfluoroalkane, the ring breathing mode of pyridine blue-shifts proportionately with the strength of the interaction. The measured blue shift for halogen bonding of pyridine and all three iodo-perfluoroalkanes is comparable to that for hydrogen bonding between pyridine and water. 2-Iodo-perfluoropropane displays thermodynamic behavior that is different from that of the 1-iodo-perfluoroalkanes, which suggests a fundamental difference at the molecular level. A potential explanation of this difference is offered and discussed.

  19. Solution-Phase Synthesis of a Tricyclic Pyrrole-2-Carboxamide Discovery Library Applying a Stetter-Paal-Knorr Reaction Sequence

    PubMed Central

    Iyer, Pravin S.; Fodor, Matthew D.; Coleman, Claire M.; Twining, Leslie A.; Mitasev, Branko

    2012-01-01

    The solution phase synthesis of a discovery library of 178 tricyclic pyrrole-2-carboxamides was accomplished in nine steps and seven purifications starting with three benzoyl protected amino acid methyl esters. Further diversity was introduced by two glyoxaldehydes and forty-one primary amines. The combination of Pauson-Khand, Stetter and microwave assisted Paal Knorr reactions was applied as a key sequence. The discovery library was designed with the help of QikProp 2.1 and physicochemical data are presented for all pyrroles. Library members were synthesized and purified in parallel and analyzed by LC-MS. Selected compounds were fully characterized. PMID:16677007

  20. Sequential aza-Baylis-Hillman/ring closing metathesis/aromatization as a novel route for the synthesis of substituted pyrroles.

    PubMed

    Declerck, Valérie; Ribière, Patrice; Martinez, Jean; Lamaty, Frédéric

    2004-11-26

    A new route to diverse 2-substituted-3-methoxycarbonyl pyrroles has been developed. Diverse SES protected alpha-methylene beta-aminoesters were obtained by a 3-component aza-Baylis-Hillman reaction. Diversity arose from the aryl aldehydes which can be used in this reaction. N-Alkylation with allyl bromide under mild conditions provided the corresponding dienes. These substituted dienes were cyclized by ring closing metathesis at room temperature or under microwave-activation with Grubbs-type II catalyst to yield SES-protected pyrroline intermediates. The final pyrroles were obtained by base-promoted dehydrodesulfinylation/aromatization. The scope of each of these reactions was explored.

  1. Biological activity of two new pyrrole derivatives against stored-product species: influence of temperature and relative humidity.

    PubMed

    Boukouvala, M C; Kavallieratos, N G; Athanassiou, C G; Hadjiarapoglou, L P

    2016-08-01

    Members of the pyrrole group are likely to have interesting properties that merit additional investigation as insecticides at the post-harvest stages of agricultural commodities. In the present work, the insecticidal effect of two new pyrrole derivatives, ethyl 3-(benzylthio)-4,6-dioxo-5-phenyl-2,4,5,6-tetrahydropyrrolo[3,4-c]pyrrole-carboxylate (3i) and isopropyl 3-(benzylthio)-4,6-dioxo-5-phenyl-2,4,5,6-tetrahydropyrrolo[3,4-c]pyrrole-carboxylate (3k) were studied as stored-wheat protectants against two major stored-product insect species, the confused flour beetle, Tribolium confusum Jaquelin du Val adults and larvae and the Mediterranean flour moth, Ephestia kuehniella Zeller larvae at different doses (0.1, 1 and 10 ppm), exposure intervals (7, 14 and 21 days), temperatures (20, 25 and 30°C) and relative humidity (55 and 75%) levels. For T. confusum adults, in the case of the pyrrole derivative 3i, mortality was low and it did not exceed 32.2% in wheat treated with 10 ppm 3i at 30°C and 55% relative humidity. Progeny production was very low (<1 individual/vial) in all combinations of 55% relative humidity, including control. In the case of the pyrrole derivative 3k, mortality reached 67.8% at 30°C and 55% relative humidity in wheat treated with 10 ppm after 21 days of exposure. Progeny production was low in all tested combinations (≤0.7 individuals/vial) of 55% relative humidity, including control. For T. confusum larvae, in the case of the pyrrole derivative 3i, at the highest dose, mortality was 82.2% at 25°C and 55% relative humidity whereas in the case of 3k it reached 77.8% at the same combination. In contrast, mortality at 75% relative humidity remained very low and did not exceed 13.3%. For E. kuehniella larvae, the highest mortalities, 44.4 and 63.3%, were observed in 10 ppm at 25°C and 55% relative humidity for both pyrrole derivatives. The compounds tested here have a certain insecticidal effect, but this effect is moderated by the exposure

  2. Violacein, an indole-derived purple-colored natural pigment produced by Janthinobacterium lividum, inhibits the growth of head and neck carcinoma cell lines both in vitro and in vivo.

    PubMed

    Masuelli, Laura; Pantanella, Fabrizio; La Regina, Giuseppe; Benvenuto, Monica; Fantini, Massimo; Mattera, Rosanna; Di Stefano, Enrica; Mattei, Maurizio; Silvestri, Romano; Schippa, Serena; Manzari, Vittorio; Modesti, Andrea; Bei, Roberto

    2016-03-01

    Violacein (VIO; 3-[1,2-dihydro-5-(5-hydroxy-1H-indol-3-yl)-2-oxo-3H-pyrrol-3-ylidene]-1,3-dihydro-2H-indol-2-one), an indole-derived purple-colored pigment, produced by a limited number of Gram-negative bacteria species, including Chromobacterium violaceum and Janthinobacterium lividum, has been demonstrated to have anti-cancer activity, as it interferes with survival transduction signaling pathways in different cancer models. Head and neck carcinoma (HNC) represents the sixth most common and one of the most fatal cancers worldwide. We determined whether VIO was able to inhibit head and neck cancer cell growth both in vitro and in vivo. We provide evidence that VIO treatment of human and mouse head and neck cancer cell lines inhibits cell growth and induces autophagy and apoptosis. In fact, VIO treatment increased PARP-1 cleavage, the Bax/Bcl-2 ratio, the inhibition of ERK1 and ERK2 phosphorylation, and the expression of light chain 3-II (LC3-II). Moreover, VIO was able to induce p53 degradation, cytoplasmic nuclear factor kappa B (NF-κB) accumulation, and reactive oxygen species (ROS) production. VIO induced a significant increase in ROS production. VIO administration was safe in BALB/c mice and reduced the growth of transplanted salivary gland cancer cells (SALTO) in vivo and prolonged median survival. Taken together, our results indicate that the treatment of head and neck cancer cells with VIO can be useful in inhibiting in vivo and in vitro cancer cell growth. VIO may represent a suitable tool for the local treatment of HNC in combination with standard therapies.

  3. A novel gene silencer, pyrrole-imidazole polyamide targeting human lectin-like oxidized low-density lipoprotein receptor-1 gene improves endothelial cell function.

    PubMed

    Ueno, Takahiro; Fukuda, Noboru; Tsunemi, Akiko; Yao, En-Hui; Matsuda, Hiroyuki; Tahira, Kazunobu; Matsumoto, Taro; Matsumoto, Koichi; Matsumoto, Yoshiaki; Nagase, Hiroki; Sugiyama, Hiroshi; Sawamura, Tatsuya

    2009-03-01

    Pyrrole-imidazole polyamide can be combined in antiparallel side-by-side dimeric complexes along the minor groove of DNA in a sequence-specific manner. Pyrrole-imidazole polyamides are effective inhibitors of transcription factors as well as viral repressors and transactivators. Recently, lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) was reported to be a major factor contributing to the pathogenesis of coronary atherosclerosis. In this study, we designed a pyrrole-imidazole polyamide specific for the LOX-1 gene and evaluated its effect on LOX-1 gene transcription. A pyrrole-imidazole polyamide was designed to target the AP-1 binding site of the LOX-1 gene and synthesized by solid phase methods. This pyrrole-imidazole polyamide significantly inhibited LOX-1 promoter activity in HEK293 cells, determined by the luciferase assay. LOX-1 mRNA expression was also inhibited by the pyrrole-imidazole polyamide at a concentration of 10-9 mol/l in human umbilical vein endothelial cells (HUVEC), determined by the real-time PCR method. HUVEC were treated by pyrrole-imidazole polyamide targeting the LOX-1 gene, and apoptosis was assessed using Hoechst stain, terminal deoxy nucleotidyl transferase-mediated UTP end labeling method, and dye-uptake bioassay. Treatment of HUVEC for 72 h with LOX-1 targeted pyrrole-imidazole polyamide decreased apoptosis induced by angiotensin II and oxidized low-density lipoprotein (ox-LDL) loading in all assays. This novel therapeutic agent, pyrrole-imidazole polyamide, could specifically inhibit LOX-1 gene expression by reducing the promoter activity of the gene. Pyrrole-imidazole polyamide seems to be a powerful promising new agent that can be used to explore therapies based on inhibition of transcription. Molecular recognition of DNA by small molecules could provide insight into the development of new human medicines.

  4. Alkylation of pyridines at their 4-positions with styrenes plus yttrium reagent or benzyl Grignard reagents.

    PubMed

    Mizumori, Tomoya; Hata, Takeshi; Urabe, Hirokazu

    2015-01-02

    A new regioselective alkylation of pyridines at their 4-position was achieved with styrenes in the presence of yttrium trichloride, BuLi, and diisobutylaluminium hydride (DIBAL-H) in THF. Alternatively, similar products were more simply prepared from pyridines and benzyl Grignard reagents. These reactions are not only a useful preparation of 4-substituted pyridines but are also complementary to other relevant reactions usually giving 2-substituted pyridines.

  5. Lewis acid activation of pyridines for nucleophilic aromatic substitution and conjugate addition.

    PubMed

    Abou-Shehada, Sarah; Teasdale, Matthew C; Bull, Steven D; Wade, Charles E; Williams, Jonathan M J

    2015-03-01

    A clean, mild and sustainable method for the functionalization of pyridines and their analogues is reported. A zinc-based Lewis acid is used to activate pyridine and its analogues towards nucleophilic aromatic substitution, conjugate addition, and cyclization reactions by binding to the nitrogen on the pyridine ring and activating the pyridine ring core towards further functionalization. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. Dehydration of water-pyridine mixtures by pervaporation

    SciTech Connect

    Kujawski, W. Centre National de la Recherche Scientifique-UA 494, Nancy ); Nguyen, T.Q.; Neel, J. )

    1991-08-01

    The pervaporation technique, in which the liquid feed mixture is maintained in contact with one side of a nonporous membrane and the permeate is continuously removed from the other side as a vapor, is one of the new methods to attain separation of azeotropic mixtures, structural isomers, or even to displace the equilibrium of chemical reactions. Several ion-exchange and neutral membranes were examined in the pervaporation of water-pyridine mixtures. Carboxylic and sulfonic ion-exchange membranes were used with hydrogen counterion and additionally with trimethylammonium, triethylammonium, and tributylammonium counterions. All membranes were selective to water, but the transport mode and selectivity properties of membranes were dependent on both the character of the ion-exchange group and the ionic form of the membrane. The results obtained suggest that pervaporation of water-pyridine mixtures could be used with standard distillation in the large-scale dehydration process of pyridine.

  7. Pyrrolo[3,2-b]pyrroles-From Unprecedented Solvatofluorochromism to Two-Photon Absorption.

    PubMed

    Friese, Daniel H; Mikhaylov, Alexander; Krzeszewski, Maciej; Poronik, Yevgen M; Rebane, Aleksander; Ruud, Kenneth; Gryko, Daniel T

    2015-12-07

    A combined experimental and theoretical study of the two-photon absorption (2PA) properties of a series of quadrupolar molecules possessing a highly electron-rich heterocyclic core, pyrrolo[3,2-b]pyrrole, is presented. In agreement with quantum-chemical calculations, large 2PA cross-section values, σ2PA ≈10(2) -10(3)  GM (1 GM=10(50)  cm(4)  s photon(-1) ), are observed at wavelengths of 650-700 nm, which correspond to the two-photon allowed but one-photon forbidden transitions. The calculations also predict that increased planarity of this molecule through removal of two N-substituents leads to further increase in the σ2PA values. Surprisingly, the most quadrupolar pyrrolo[3,2-b]pyrrole derivative, containing two 4-nitrophenyl substituents at positions 2 and 5, demonstrates a very strong solvatofluorochromic effect, with a fluorescence quantum yield as high as 0.96 in cyclohexane, whereas the fluorescence vanishes in DMSO.

  8. Synthesis, insecticidal, and acaricidal activities of novel 2-aryl-pyrrole derivatives containing ester groups.

    PubMed

    Zhao, Yu; Li, Yongqiang; Ou, Xiaoming; Zhang, Pengxiang; Huang, Zhiqiang; Bi, Fuchun; Huang, Runqiu; Wang, Qingmin

    2008-11-12

    A series of novel 2-aryl-pyrrole derivatives containing ester groups were synthesized, and their structures were characterized by (1)H NMR spectroscopy and elemental analysis. The insecticidal activities against oriental armyworm, mosquito, diamondback moth, green rice leafhopper, and bean aphids and acaricidal activities against spider mite of these new compounds were evaluated. The results of bioassays indicated that some of these title compounds exhibited excellent insecticidal and acaricidal activities. The insecticidal activities against oriental armyworm of compounds IVa, IVd, IVe, IVf, IVg, IVi, IVk, and IVp were equal to commercialized Chlorfenapyr, and the insecticidal activities of most of compounds IVb, IVc, IVd, IVf, IVg, IVj, IVk, IVl, IVs, IVt, IVu, IVw, IVx, IVz, and Chlorfenapyr against mosquito at 0.10 mg kg (-1) were 100%, and the acaricidal activities of compounds IVd, IVe, IVf, IVg, IVh, IVi, and IVk were equal or superior to Chlorfenapyr. Especially, the results indicated that the acaricidal activity of [4-bromo-2-(4-chlorophenyl)-3-cyano-5-(trifluoromethyl)pyrrol-1-yl]methyl 3-methylbutanoate ( IVg) against spider mite was 2.65-fold as high as that of Chlorfenapyr from the value of LC 50.

  9. NH stretching vibrations of pyrrole clusters studied by infrared cavity ringdown spectroscopy.

    PubMed

    Matsumoto, Yoshiteru; Honma, Kenji

    2007-11-14

    The IR spectra for various sizes of pyrrole clusters were measured in the NH stretching vibration region by infrared cavity ringdown spectroscopy. The hydrogen-bonded structures and normal modes of the pyrrole clusters were analyzed by a density functional theory calculation of the B3LYP/6-311+G(d,p) level. Two types of pulsed nozzles, a slit and a large pinhole, were used to generate different cluster size distributions in a supersonic jet. A rotational contour analysis of the NH stretching vibration for the monomer revealed that the slit nozzle provides a warmer jet condition than the pinhole one. The IR spectra, measured under the warmer condition, showed the intense bands at 3444, 3392, and 3382 cm(-1), which were assigned to hydrogen-bonded NH stretching vibrations due to the dimer, the trimer, and the tetramer, respectively. On the other hand, the IR spectra measured under a lower temperature condition by a pinhole nozzle showed a broad absorption feature in addition to sharp bands. This broad absorption was reproduced by the sum of two Gaussians peaks at 3400 and 3372 cm(-1) with widths of 30 and 50 cm(-1) (FWHM), respectively. Compared with the spectra of the condensed phase, two bands at 3400 and 3372 cm(-1) were assigned to hydrogen-bonded NH stretching vibrations of larger clusters having liquid-like and solid-like structures, respectively.

  10. Effects of hydrogen bonding between pyrrole-2-carboxaldehyde and nearest polar and nonpolar environment

    NASA Astrophysics Data System (ADS)

    Rana, Meenakshi; Chowdhury, Papia

    2017-10-01

    The present paper represents dominant effects of hydrogen bonding on the existence of different molecular aggregates in one of the heterocyclic pyrrole system: pyrrole-2-carboxaldehyde (PCL). Theoretical and experimental Raman spectral evidence verifies the existence of different molecular aggregates like dimeric, monomeric, hydrated complex states in PCL. Atoms in molecules (AIMs) analysis and fluorescence decay profile provide a strong signature of intermolecular hydrogen bonding (IerHB) as the possible reason for the existence of cis form of dimeric (X) molecular aggregates. The high remnant polarization of 3.13 μCcm- 2 and smaller dielectric loss in solid form of PCL arise due to in X by ordering of dipoles as a result of IerHB. A remarkable high ferroelectric response in solid phase makes PCL a desirable candidate to be used as raw material for energy storage devices. For solution phase, in presence of external hydroxylic environment, PCL reacts with external water molecules through weak IerHB and creates different hydrated PCL/(H2O)n complexes by creating water bridge with number of water molecules from 1 to n. An increasing number of water molecules helps to form stronger hydrated complex by separation of charges by lowering the transferring energy barrier.

  11. Pyrrole-hyaluronic acid conjugates for decreasing cell binding to metals and conducting polymers

    PubMed Central

    Lee, Jae Young; Schmidt, Christine E.

    2010-01-01

    Surface modification of electrically conductive biomaterials has been studied to improve biocompatibility for a number of applications, such as implantable sensors and microelectrode arrays. In this study, we electrochemically coated electrodes with biocompatible and non-cell adhesive hyaluronic acid (HA) to reduce cellular adhesion for potential use in neural prostheses. To this end, pyrrole-conjugated hyaluronic acid (PyHA) was synthesized and employed for electrochemical coating of platinum, indium-tin-oxide, and polystyrene sulfonate-doped polypyrrole electrodes. This PyHA conjugate consists of (1) a pyrrole moiety that allows the compound to be electrochemically deposited onto a conductive substrate and (2) non-adhesive HA to minimize cell adhesion and to potentially decrease inflammatory tissue responses. Our characterization results showed the presence of a hydrophilic p(PyHA) layer on the modified electrode, and impedance measurements revealed impedance that was statistically the same as the unmodified electrode. We found that the p(PyHA)-coated electrodes minimized adhesion and migration of fibroblasts and astrocytes for a minimum of up to 3 months. Also, the coating was stable in physiological solution for 3 months and also stable against enzymatic degradation by hyaluronidase. These studies suggest that this p(PyHA)-coating has the potential to be used to mask conducting electrodes from adverse glial responses that occur upon implantation. In addition, electrochemical coating with PyHA can be potentially extended for the surface modification of other metallic and conducting substances such as stents and biosensors. PMID:20558330

  12. Calix[4]pyrrole Schiff base macrocycles. Novel binucleating ligands for mu-oxo iron complexes.

    PubMed

    Veauthier, Jacqueline M; Cho, Won-Seob; Lynch, Vincent M; Sessler, Jonathan L

    2004-02-23

    New bimetallic mu-oxo diferric complexes of several previously reported calix[4]pyrrole Schiff base macrocycles are described. The synthesis of a new member of this class of macrocycles is also reported; it was prepared via an acid-catalyzed condensation between 1,9-bisformyl-5,5-dipropyldipyrromethane and o-phenylenediamine. Reactions of the free base macrocycles or their bis-HCl salts with Fe(II) mesitylene, followed by air oxidation, gave the binuclear mu-oxo bis-Fe(III) compounds 6-10 in moderate yield. X-ray crystallography data reveal two different coordination environments for the Fe-O-Fe subunit in 6-10 that it is suggested can be controlled by altering the reaction conditions. Structural properties of these metalated pyrrolic macrocycles are also compared to those of mu-oxo diferric porphyrins and mu-oxo diferric texaphyrin. Complexes 6-10 exhibit two distinct types of M-N bonds that are similar in length to the bonds observed in metallotexaphyrin complexes. However, the electronics of the present systems are very different from those of texaphyrins and porphyrins in that no delocalized bonding patterns are observed within the ligands as a whole.

  13. Active transport of amino acids by a guanidiniocarbonyl-pyrrole receptor.

    PubMed

    Urban, Christian; Schmuck, Carsten

    2010-08-16

    Herein we report the synthesis and characterization of a transporter 9 for N-acetylated amino acids. Transporter 9 is a conjugate of a guanidiniocarbonyl pyrrole cation, one of the most efficient carboxylate binding motifs reported so far, and a hydrophobic tris(dodecylbenzyl) group, which ensures solubility in organic solvents. In its protonated form, 9 binds N-acetylated amino acid carboxylates in wet organic solvents with association constants in the range of 10(4) M(-1) as estimated by extraction experiments. Aromatic amino acids are preferred due to additional cation-pi-interactions of the amino acid side chain with the guanidiniocarbonyl pyrrole moiety. U-tube experiments established efficient transport across a bulk liquid chloroform phase with fluxes approaching 10(-6) mol m(-2) s(-1). In experiments with single substrates, the release rate of the amino acid from the receptor-substrate complex at the interface with the receiving phase is rate determining. In contrast to this, in competition experiments with several substrates, the thermodynamic affinity to 9 becomes decisive. As 9 can only transport anions in its protonated form and has a pK(a) value of approximately 7, pH-driven active transport of amino acids is also possible. Transport occurs as a symport of the amino acid carboxylate and a proton.

  14. Pyridine analogs inhibit the glucosyltransferase of Streptococcus mutans.

    PubMed Central

    Thaniyavarn, S; Taylor, K G; Singh, S; Doyle, R J

    1982-01-01

    Soluble glucan synthesis catalyzed by dextransucrase preparations from Streptococcus mutans 6715 were inhibited by pyridoxal-5-phosphate and several other pyridine analogs, including pyridoxine, pyridoxamine, pyridoxamine-5-phosphate, pyridoxal, and 4-pyridoxic acid. Pyridine and pyridine-4-carboxaldehyde were not effective inhibitors of the enzyme. Kinetic analyses suggested that pyridoxal-5-phosphate is a noncompetitive inhibitor of dextransucrase. The inactivation was dependent on time, pyridoxal-5-phosphate concentration, and hydrogen ion concentration. Apparent Ki values were 4.9 mM at pH 7.0 and 4.2 mM at pH 5.5. Dextransucrase activity could be restored by dialysis to remove the inhibitors. Maximum inhibition was observed after a 120-min incubation of the enzyme with pyridoxal-5-phosphate. The pH optima for inhibition by pyridoxal-5-phosphate were 4 and 7. The sucrose-dependent adherence of S. mutans cells to saliva-coated hydroxylapatite beads was also inhibited by pyridoxal-5-phosphate but only marginally by the other pyridine anatogs. In addition, pyridoxal-5-phosphate markedly reduced the rate of acid production by intact S. mutans cells from sucrose or glucose substrates. Another pyridoxal-5-phosphate analog, 2-methyl-5-hydroxypyridine, was also effective in preventing the production of acid by S. mutans from sucrose or glucose. When S. mutans cells were preincubated with pyridoxal-5-phosphate or pyridine analogs, significant reductions in the rate of D-glucose uptake were observed. It is suggested that the inhibition of dextransucrase occurs because of a change iun enzyme conformation which results from the binding of the pyridine derivatives. The results suggest that pyridoxal-5-phosphate or structural analogs may ultimately be useful in reducing the incidence of dental caries. PMID:6215355

  15. Is the 2,3-carbon-carbon bond of indole really inert to oxidative cleavage by Oxone?--synthesis of isatoic anhydrides from indoles.

    PubMed

    Nelson, Amber C; Kalinowski, Emily S; Czerniecki, Nikolas J; Jacobson, Taylor L; Grundt, Peter

    2013-11-21

    A recent report has indicated that the oxidizing agent Oxone does not possess the ability to cleave the 2,3-carbon-carbon bond of indole. Work in our laboratory shows that this is not the case. Indole and a variety of aryl ring substituted derivatives readily react to form synthetically important isatoic anhydrides.

  16. The multifaceted roles of the interspecies signalling molecule indole in Agrobacterium tumefaciens.

    PubMed

    Lee, Jin-Hyung; Kim, Yong-Guy; Baek, Kwang-Hyun; Cho, Moo Hwan; Lee, Jintae

    2015-04-01

    Bacteria utilize signal molecules to ensure their survival in environmental niches, and indole is an interspecies and interkingdom signalling molecule, which is widespread in the natural environment. In this study, we sought to identify novel roles of indole in soil-borne bacterium Agrobacterium tumefaciens. Agrobacterium tumefaciens was found not to synthesize indole and to degrade it rapidly. The addition of exogenous indole dose-dependently inhibited A. tumefaciens growth and decreased its motility. Surprisingly, indole markedly increased A. tumefaciens biofilm formation on polystyrene, glass and nylon membrane surfaces and enhanced its antibiotic tolerance. Transcriptional analysis showed that indole markedly up-regulated several biofilm-related (celA, cheA, exoR, phoB, flgE, fliR and motA), stress-related genes (clpB, dnaK, gsp, gyrB, marR and soxR) and efflux genes (emrA, norM, and Atu2551) in A. tumefaciens, which partially explained the increased biofilm formation and antibiotic tolerance. In contrast, the plant auxin indole-3-acetic acid did not affect biofilm formation, antibiotic tolerance or gene expression. Interestingly, indole was found to exhibit several similarities with antibiotics, as it inhibited the growth of non-indole-producing bacteria, whereas these bacteria countered its effects by rapidly degrading indole, and by enhancing biofilm formation and antibiotic tolerance.

  17. 40 CFR 721.10399 - Benzoic acid azo-substituted pyridine (generic).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Benzoic acid azo-substituted pyridine... Specific Chemical Substances § 721.10399 Benzoic acid azo-substituted pyridine (generic). (a) Chemical... as benzoic acid azo-substituted pyridine (PMN P-10-501) is subject to reporting under this section...

  18. 40 CFR 721.10399 - Benzoic acid azo-substituted pyridine (generic).

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Benzoic acid azo-substituted pyridine... Specific Chemical Substances § 721.10399 Benzoic acid azo-substituted pyridine (generic). (a) Chemical... as benzoic acid azo-substituted pyridine (PMN P-10-501) is subject to reporting under this section...

  19. 40 CFR 721.10399 - Benzoic acid azo-substituted pyridine (generic).

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Benzoic acid azo-substituted pyridine... Specific Chemical Substances § 721.10399 Benzoic acid azo-substituted pyridine (generic). (a) Chemical... as benzoic acid azo-substituted pyridine (PMN P-10-501) is subject to reporting under this section...

  20. A Pd(0)-Mediated Indole (Macro)cyclization Reaction

    PubMed Central

    Breazzano, Steven P.; Poudel, Yam B.; Boger, Dale L.

    2013-01-01

    Herein, we report a systematic study of the Larock indole annulation designed to explore the scope and define the generality of its use in macrocyclization reactions, its use in directly accessing the chloropeptin I versus II DEF ring system as well as key unnatural isomers, its utility for both peptide-derived and more conventional carbon-chain based macrocycles, and its extension to intramolecular cyclizations with formation of common ring sizes. The studies define a powerful method complementary to the Stille or Suzuki cross-coupling reactions for the synthesis of cyclic or macrocyclic ring systems containing an embedded indole, tolerating numerous functional groups and incorporating various (up to 28-membered) ring sizes. As a result of the efforts to expand the usefulness and scope of the reaction, we also disclose a catalytic variant of the reaction along with a powerful Pd2(dba)3 derived catalyst system, and an examination of the factors impacting reactivity and catalysis. PMID:23298368

  1. Regulatory and Functional Aspects of Indolic Metabolism in Plant Systemic Acquired Resistance.

    PubMed

    Stahl, Elia; Bellwon, Patricia; Huber, Stefan; Schlaeppi, Klaus; Bernsdorff, Friederike; Vallat-Michel, Armelle; Mauch, Felix; Zeier, Jürgen

    2016-05-02

    Tryptophan-derived, indolic metabolites possess diverse functions in Arabidopsis innate immunity to microbial pathogen infection. Here, we investigate the functional role and regulatory characteristics of indolic metabolism in Arabidopsis systemic acquired resistance (SAR) triggered by the bacterial pathogen Pseudomonas syringae. Indolic metabolism is broadly activated in both P. syringae-inoculated and distant, non-inoculated leaves. At inoculation sites, camalexin, indol-3-ylmethylamine (I3A), and indole-3-carboxylic acid (ICA) are the major accumulating compounds. Camalexin accumulation is positively affected by MYB122, and the cytochrome P450 genes CYP81F1 and CYP81F2. Local I3A production, by contrast, occurs via indole glucosinolate breakdown by PEN2- dependent and independent pathways. Moreover, exogenous application of the defense hormone salicylic acid stimulates I3A generation at the expense of its precursor indol-3-ylmethylglucosinolate (I3M), and the SAR regulator pipecolic acid primes plants for enhanced P. syringae-induced activation of distinct branches of indolic metabolism. In uninfected systemic tissue, the metabolic response is more specific and associated with enhanced levels of the indolics I3A, ICA, and indole-3-carbaldehyde (ICC). Systemic indole accumulation fully depends on functional CYP79B2/3, PEN2, and MYB34/51/122, and requires functional SAR signaling. Genetic analyses suggest that systemically elevated indoles are dispensable for SAR and associated systemic increases of salicylic acid. However, soil-grown but not hydroponically -cultivated cyp79b2/3 and pen2 plants, both defective in indolic secondary metabolism, exhibit pre-induced immunity, which abrogates their intrinsic ability to induce SAR.

  2. Transport and metabolism of indole-3-acetyl-myo-inositol-galactoside in seedlings of Zea mays

    NASA Technical Reports Server (NTRS)

    Komoszynski, M.; Bandurski, R. S.

    1986-01-01

    Indole-3-acetyl-myo-inositol galactoside labeled with 3H in the indole and 14C in the galactose moieties was applied to kernels of 5 day old germinating seedlings of Zea mays. Indole-3-acetyl-myo-inositol galactoside was not transported into either the shoot or root tissue as the intact molecule but was instead hydrolyzed to yield [3H]indole-3-acetyl-myo-inositol and [3H]indole-3-acetic acid which were then transported to the shoot with little radioactivity going to the root. With certain assumption concerning the equilibration of applied [3H]indole-3-acetyl-myo-inositol-[U-14C]galactose with the endogenous pool, it may be concluded that indole-3-acetyl-myo-inositol galactoside in the endosperm supplies about 2 picomoles per plant per hour of indole-3-acetyl-myo-inositol and 1 picomole per plant per hour of indole-3-acetic acid to the shoot and thus is comparable to indole-3-acetyl-myo-inositol as a source of indole-acetic acid for the shoot. Quantitative estimates of the amount of galactose in the kernels suggest that [3H]indole-3-acetyl-myo-inositol-[14C]galactose is hydrolyzed after the compound leaves the endosperm but before it reaches the shoot. In addition, [3H]indole-3-acetyl-myo-inositol-[14C]galactose supplies appreciable amounts of 14C to the shoot and both 14C and 3H to an uncharacterized insoluble fraction of the endosperm.

  3. Transport and metabolism of indole-3-acetyl-myo-inositol-galactoside in seedlings of Zea mays

    NASA Technical Reports Server (NTRS)

    Komoszynski, M.; Bandurski, R. S.

    1986-01-01

    Indole-3-acetyl-myo-inositol galactoside labeled with 3H in the indole and 14C in the galactose moieties was applied to kernels of 5 day old germinating seedlings of Zea mays. Indole-3-acetyl-myo-inositol galactoside was not transported into either the shoot or root tissue as the intact molecule but was instead hydrolyzed to yield [3H]indole-3-acetyl-myo-inositol and [3H]indole-3-acetic acid which were then transported to the shoot with little radioactivity going to the root. With certain assumption concerning the equilibration of applied [3H]indole-3-acetyl-myo-inositol-[U-14C]galactose with the endogenous pool, it may be concluded that indole-3-acetyl-myo-inositol galactoside in the endosperm supplies about 2 picomoles per plant per hour of indole-3-acetyl-myo-inositol and 1 picomole per plant per hour of indole-3-acetic acid to the shoot and thus is comparable to indole-3-acetyl-myo-inositol as a source of indole-acetic acid for the shoot. Quantitative estimates of the amount of galactose in the kernels suggest that [3H]indole-3-acetyl-myo-inositol-[14C]galactose is hydrolyzed after the compound leaves the endosperm but before it reaches the shoot. In addition, [3H]indole-3-acetyl-myo-inositol-[14C]galactose supplies appreciable amounts of 14C to the shoot and both 14C and 3H to an uncharacterized insoluble fraction of the endosperm.

  4. Nuclear alkylated pyridine aldehyde polymers and conductive compositions thereof

    NASA Technical Reports Server (NTRS)

    Rembaum, A.; Singer, S. (Inventor)

    1970-01-01

    A thermally stable, relatively conductive polymer was disclosed. The polymer was synthesized by condensing in the presence of catalyst a 2, 4, or 6 nuclear alklylated 2, 3, or 4 pyridine aldehyde or quaternary derivatives thereof to form a polymer. The pyridine groups were liked by olefinic groups between 2-4, 2-6, 2-3, 3-4, 3-6 or 4-6 positions. Conductive compositions were prepared by dissolving the quaternary polymer and an organic charge transfer complexing agent such as TCNQ in a mutual solvent such as methanol.

  5. Regioselective photocycloaddition of pyridine derivatives to electron-rich alkenes.

    PubMed

    Sakamoto, Masami; Sano, Takeru; Fujita, Shohei; Ando, Masaru; Yamaguchi, Kentaro; Mino, Takashi; Fujita, Tsutomu

    2003-02-21

    Irradiation of a benzene solution of 3-cyano-2,6-dimethoxypyridine in the presence of ethyl vinyl ether (EVE) gave 1:1 photoadducts, 3-cyano-5-ethoxy-2,8-dimethoxy-4,5-dihydroazocine, in good yields, whose structure was established by X-ray single-crystal analysis. The photoadduct was produced via cycloaddition between the C3-C4 position of the pyridine derivatives and an alkene chromophore. On the other hand, 3-cyano-2,6-dimethoxy-4-methylpyridine cycloadds to EVE at the C2-C3 position of the pyridine ring upon irradiation. The difference is explained on the basis of the steric effect.

  6. The regioselective iodination of quinolines, quinolones, pyridones, pyridines and uracil.

    PubMed

    Dutta, Uttam; Deb, Arghya; Lupton, David W; Maiti, Debabrata

    2015-12-28

    A radical based direct C-H iodination protocol for quinolines, quinolones, pyridones, pyridines, and uracil has been developed. The iodination occurs in a C3 selective manner for quinolines and quinolones. Pyridones and pyridines undergo C3 and C5 iodination, while dimethyl uracil undergoes C5 iodination. Scope of the method was demonstrated through the rapid synthesis of both electron rich as well as electron poor heteroaromatic iodides. The protocol was found to be scalable and general, while a mechanism has been proposed.

  7. Effect of pyridine on infrared absorption spectra of copper phthalocyanine.

    PubMed

    Singh, Sukhwinder; Tripathi, S K; Saini, G S S

    2008-02-01

    Infrared absorption spectra of copper phthalocyanine in KBr pellet and pyridine solution in 400-1625 and 2900-3200 cm(-1)regions are reported. In the IR spectra of solid sample, presence of weak bands, which are forbidden according to the selection rules of D4h point group, is explained on the basis of distortion in the copper phthalocyanine molecule caused by the crystal packing effects. Observation of a new band at 1511 cm(-1) and change in intensity of some other bands in pyridine are interpreted on the basis of coordination of the solvent molecule with the central copper ion.

  8. Magnetic field effect on indole exciplexes: a comparative study

    NASA Astrophysics Data System (ADS)

    Sengupta, Tamal; Basu, Samita

    2004-04-01

    A comparative magnetic field effect (MFE) study was done on indole exciplexes with various acceptors, anthracene, pyrene, all-s- trans-1,4-diphenylbuta-1,3-diene and 9-cyanophenanthrene. A surprisingly low magnetic field effect was detected for the 9-cyanophenanthrene exciplexes and was correlated with exciplex geometry. The wavelength dependence of magnetic field effect confirms the presence of single charge-transfer complex for all the exciplexes with 1,2-dimethylindole.

  9. Synthesis of an indole analog of folic acid

    SciTech Connect

    Shengeliya, M.S.; Avramenko, V.G.; Kuleshova, L.N.; Ershova, Yu.A.; Chernov, V.A.; Surorov, N.N.

    1987-06-01

    The authors study the replacement of the p-aminobenzoic acid (PABA) moiety. The authors synthesized an indole analog of folic acid, namely dimethyl N-(5-(2'-amino-4'-oxo-6'-pteridinyl)methylaminoindol-2-yl)glutamate. The physicochemical properties and the chemical shifts in the PMR spectra of the compounds obtained are shown. The examination of the compound for antitumor activity was carried out using rats and mice.

  10. Hybrid Monoterpenoid Indole Alkaloids Obtained as Artifacts from Rauvolfia tetraphylla.

    PubMed

    Gao, Yuan; Zhou, Dong-Sheng; Hai, Ping; Li, Yan; Wang, Fei

    2015-10-01

    Five new hybrid monoterpenoid indole alkaloids bearing an unusual 2,2-dimethyl-4-oxopiperidin-6-yl moiety, namely rauvotetraphyllines F-H (1, 3, 4), 17-epi-rauvotetraphylline F (2) and 21-epi-rauvotetraphylline H (5), were isolated from the aerial parts of Rauvolfia tetraphylla. Their structures were established by extensive spectroscopic analysis. The new alkaloids were evaluated for their cytotoxicity in vitro against five human cancer cell lines.

  11. Monoterpenoid Indole Alkaloids from Inadequately Dried Leaves of Alstonia scholaris.

    PubMed

    Qin, Xu-Jie; Zhao, Yun-Li; Song, Chang-Wei; Wang, Bei; Chen, Ying-Ying; Liu, Lu; Li, Qiong; Li, Dan; Liu, Ya-Ping; Luo, Xiao-Dong

    2015-08-01

    Six new indole alkaloids, named alstoniascholarines L-Q (1-6), together with nineteen known analogues were isolated from the inadequately dried leaves of Alstonia scholaris. Their structures were elucidated on the basis of extensive analysis of spectroscopic data and by comparison of their physical and spectroscopic data with the literature values. In addition, the new alkaloids were tested for their cytotoxic and neurite outgrowth-promoting activities.

  12. Alistonitrine A, a caged monoterpene indole alkaloid from Alstonia scholaris.

    PubMed

    Zhu, Guo-Yuan; Yao, Xiao-Jun; Liu, Liang; Bai, Li-Ping; Jiang, Zhi-Hong

    2014-02-21

    Alistonitrine A, a new monoterpene indole alkaloid incorporating a third nitrogen atom, was isolated from the leaves of Alstonia scholaris and found to possess an unprecedented caged skeleton with a unique 6/5/6/5/5/6 ring system. Its structure and absolute configuration were established by extensive spectroscopic analyses and electron circular dichroism calculations. A plausible biogenetic pathway has been proposed for the biosynthesis of alistonitrine A from picrinine.

  13. Indole and beta-carboline alkaloids from Geissospermum sericeum.

    PubMed

    Steele, Jonathan C P; Veitch, Nigel C; Kite, Geoffrey C; Simmonds, Monique S J; Warhurst, David C

    2002-01-01

    The indole alkaloid geissoschizoline (1) and two new derivatives, geissoschizoline N(4)-oxide (2) and 1,2-dehydrogeissoschizoline (3), were obtained from the bark of Geissospermum sericeum together with the beta-carboline alkaloid flavopereirine (4). The in vitro antiplasmodial activity of these compounds was evaluated in chloroquine-resistant (K1) and chloroquine-sensitive (T9-96) Plasmodium falciparum. Their cytotoxicity was determined in a human (KB) cell line.

  14. [1-Meth­oxy-3-(pyridin-2-yl)indolizin-2-yl](pyridin-2-yl)methanone

    PubMed Central

    Kloubert, Tobias; Kretschmer, Robert; Görls, Helmar; Westerhausen, Matthias

    2012-01-01

    Methyl­ation of [1-hy­droxy-3-(pyridin-2-yl)indolizin-2-yl](pyridin-2-yl)methanone was performed via metalation with potassium tert-butano­late in toluene and a subsequent metathesis reaction with methyl iodide yielded the yellow title compound, C20H15N3O2. The substituents at the indolizine unit are twisted [the indolizine ring system makes dihedral angles of 34.67 (7) and 77.49 (5)°, respectively, with the pyridyl and pyridinoyl rings] with single bonds between the central unit and the attached pyridine ring [1.459 (3) Å] and the pyridinoyl group [1.483 (3) Å]. There are no classical hydrogen bonds in the crystal structure. PMID:22969532

  15. Developments of indoles as anti-HIV-1 inhibitors.

    PubMed

    Xu, Hui; Lv, Min

    2009-01-01

    Since the first case of acquired immunodeficiency syndrome (AIDS) was reported in 1981, AIDS has always been a global health threat and the leading cause of deaths due to the rapid emergence of drug-resistance and unwanted metabolic side effects. Every day in 2007 an estimated 6850 people were newly infected with human immunodeficiency virus (HIV). Over the past 28 years the rapid worldwide spread of AIDS has prompted an intense research effort to discover compounds that could effectively inhibit HIV. The development of new, selective and safe inhibitors for the treatment of HIV, therefore, still remains a high priority for medical research. To the best of our knowledge, the indole derivatives have been considered as one class of promising HIV-1 inhibitors, such as delavirdine approved by the Food and Drug Administration (FDA) in 1997 for use in combination with other antiretrovirals in adults with HIV infection. In this review we focus on the synthesis and anti-HIV-1 activity of indole derivatives, in the meantime, the structure-activity relationship (SAR) for some derivatives are also surveyed. It will pave the way for the design of indole derivatives as anti-HIV-1 drugs in the future.

  16. The reaction of indole with the aminoacrylate intermediate of Salmonella typhimurium tryptophan synthase: observation of a primary kinetic isotope effect with 3-[(2)H]indole.

    PubMed

    Cash, Michael T; Miles, Edith W; Phillips, Robert S

    2004-12-15

    The bacterial tryptophan synthase alpha(2)beta(2) complex catalyzes the final reactions in the biosynthesis of L-tryptophan. Indole is produced at the active site of the alpha-subunit and is transferred through a 25-30 A tunnel to the beta-active site, where it reacts with an aminoacrylate intermediate. Lane and Kirschner proposed a two-step nucleophilic addition-tautomerization mechanism for the reaction of indole with the aminoacrylate intermediate, based on the absence of an observed kinetic isotope effect (KIE) when 3-[(2)H]indole reacts with the aminoacrylate intermediate. We have now observed a KIE of 1.4-2.0 in the reaction of 3-[(2)H]indole with the aminoacrylate intermediate in the presence of monovalent cations, but not when an alpha-subunit ligand, disodium alpha-glycerophosphate (Na(2)GP), is present. Rapid-scanning stopped flow kinetic studies were performed of the reaction of indole and 3-[(2)H]indole with tryptophan synthase preincubated with L-serine, following the decay of the aminoacrylate intermediate at 350 nm, the formation of the quinonoid intermediate at 476 nm, and the formation of the L-Trp external aldimine at 423 nm. The addition of Na(2)GP dramatically slows the rate of reaction of indole with the alpha-aminoacrylate intermediate. A primary KIE is not observed in the reaction of 3-[(2)H]indole with the aminoacrylate complex of tryptophan synthase in the presence of Na(2)GP, suggesting binding of indole with tryptophan synthase is rate limiting under these conditions. The reaction of 2-methylindole does not show a KIE, either in the presence of Na(+) or Na(2)GP. These results support the previously proposed mechanism for the beta-reaction of tryptophan synthase, but suggest that the rate limiting step in quinonoid intermediate formation from indole and the aminoacrylate intermediate is deprotonation.

  17. Novel Indole-2-Carboxamide Compounds Are Potent Broad-Spectrum Antivirals Active against Western Equine Encephalitis Virus In Vivo

    PubMed Central

    Delekta, Phillip C.; Dobry, Craig J.; Sindac, Janice A.; Barraza, Scott J.; Blakely, Pennelope K.; Xiang, Jianming; Kirchhoff, Paul D.; Keep, Richard F.; Irani, David N.; Larsen, Scott D.

    2014-01-01

    ABSTRACT Neurotropic alphaviruses, including western, eastern, and Venezuelan equine encephalitis viruses, cause serious and potentially fatal central nervous system infections in humans for which no currently approved therapies exist. We previously identified a series of thieno[3,2-b]pyrrole derivatives as novel inhibitors of neurotropic alphavirus replication, using a cell-based phenotypic assay (W. Peng et al., J. Infect. Dis. 199:950–957, 2009, doi:http://dx.doi.org/10.1086/597275), and subsequently developed second- and third-generation indole-2-carboxamide derivatives with improved potency, solubility, and metabolic stability (J. A. Sindac et al., J. Med. Chem. 55:3535–3545, 2012, doi:http://dx.doi.org/10.1021/jm300214e; J. A. Sindac et al., J. Med. Chem. 56:9222–9241, 2013, http://dx.doi.org/10.1021/jm401330r). In this report, we describe the antiviral activity of the most promising third-generation lead compound, CCG205432, and closely related analogs CCG206381 and CCG209023. These compounds have half-maximal inhibitory concentrations of ∼1 μM and selectivity indices of >100 in cell-based assays using western equine encephalitis virus replicons. Furthermore, CCG205432 retains similar potency against fully infectious virus in cultured human neuronal cells. These compounds show broad inhibitory activity against a range of RNA viruses in culture, including members of the Togaviridae, Bunyaviridae, Picornaviridae, and Paramyxoviridae families. Although their exact molecular target remains unknown, mechanism-of-action studies reveal that these novel indole-based compounds target a host factor that modulates cap-dependent translation. Finally, we demonstrate that both CCG205432 and CCG209023 dampen clinical disease severity and enhance survival of mice given a lethal western equine encephalitis virus challenge. These studies demonstrate that indole-2-carboxamide compounds are viable candidates for continued preclinical development as inhibitors of

  18. Novel indole-2-carboxamide compounds are potent broad-spectrum antivirals active against western equine encephalitis virus in vivo.

    PubMed

    Delekta, Phillip C; Dobry, Craig J; Sindac, Janice A; Barraza, Scott J; Blakely, Pennelope K; Xiang, Jianming; Kirchhoff, Paul D; Keep, Richard F; Irani, David N; Larsen, Scott D; Miller, David J

    2014-10-01

    Neurotropic alphaviruses, including western, eastern, and Venezuelan equine encephalitis viruses, cause serious and potentially fatal central nervous system infections in humans for which no currently approved therapies exist. We previously identified a series of thieno[3,2-b]pyrrole derivatives as novel inhibitors of neurotropic alphavirus replication, using a cell-based phenotypic assay (W. Peng et al., J. Infect. Dis. 199:950-957, 2009, doi:http://dx.doi.org/10.1086/597275), and subsequently developed second- and third-generation indole-2-carboxamide derivatives with improved potency, solubility, and metabolic stability (J. A. Sindac et al., J. Med. Chem. 55:3535-3545, 2012, doi:http://dx.doi.org/10.1021/jm300214e; J. A. Sindac et al., J. Med. Chem. 56:9222-9241, 2013, http://dx.doi.org/10.1021/jm401330r). In this report, we describe the antiviral activity of the most promising third-generation lead compound, CCG205432, and closely related analogs CCG206381 and CCG209023. These compounds have half-maximal inhibitory concentrations of ∼1 μM and selectivity indices of >100 in cell-based assays using western equine encephalitis virus replicons. Furthermore, CCG205432 retains similar potency against fully infectious virus in cultured human neuronal cells. These compounds show broad inhibitory activity against a range of RNA viruses in culture, including members of the Togaviridae, Bunyaviridae, Picornaviridae, and Paramyxoviridae families. Although their exact molecular target remains unknown, mechanism-of-action studies reveal that these novel indole-based compounds target a host factor that modulates cap-dependent translation. Finally, we demonstrate that both CCG205432 and CCG209023 dampen clinical disease severity and enhance survival of mice given a lethal western equine encephalitis virus challenge. These studies demonstrate that indole-2-carboxamide compounds are viable candidates for continued preclinical development as inhibitors of neurotropic

  19. Influence of substituents on the N K X-ray absorption near-edge structure of pyrrole derivatives

    NASA Astrophysics Data System (ADS)

    Hennig, C.; Hallmeier, K. H.; Bach, A.; Bender, S.; Franke, R.; Hormes, J.; Szargan, R.

    1996-08-01

    The X-ray absorption and electron yield spectra of monomeric pyrrole including derivatives with different substituents, thiazole and oxazole have been investigated. Inductive and mesomeric effects on the spectral features are discussed. Inductive effects create energy shifts of the π ∗ resonances: mesomeric effects cause a splitting and energy shifts of the π ∗ resonances.

  20. A Guided Inquiry Experiment for the Measurement of Activation Energies in the Biophysical Chemistry Laboratory: Decarboxylation of Pyrrole-2-Carboxylate

    ERIC Educational Resources Information Center

    Hutchinson, Kelly M.; Bretz, Stacey Lowery; Mettee, Howard D.; Smiley, Jeffrey A.

    2005-01-01

    A laboratory experiment for undergraduate biophysical chemistry is described, in which the acid concentration and temperature dependences of the decarboxylation of pyrrole-2-carboxylate are measured using a continuous ultraviolet (UV) spectrophotometric assay. Data collection and analysis are structured using principles of guided inquiry. Data…

  1. Assessment of conformational, spectral, antimicrobial activity, chemical reactivity and NLO application of Pyrrole-2,5-dicarboxaldehyde bis(oxaloyldihydrazone).

    PubMed

    Rawat, Poonam; Singh, R N

    2015-04-05

    An orange colored pyrrole dihydrazone: Pyrrole-2,5-dicarboxaldehyde bis(oxaloyldihydrazone) (PDBO) has been synthesized by reaction of oxalic acid dihydrazide with 2,5 diformyl-1H-pyrrole and has been characterized by spectroscopic analysis (1H, 13C NMR, UV-visible, FT-IR and DART Mass). The properties of the compound has been evaluated using B3LYP functional and 6-31G(d,p)/6-311+G(d,p) basis set. The symmetric (3319, 3320 cm(-1)) and asymmetric (3389, 3382 cm(-1)) stretching wave number confirm free NH2 groups in PDBO. NBO analysis shows, inter/intra molecular interactions within the molecule. Topological parameters have been analyzed by QTAIM theory and provide the existence of intramolecular hydrogen bonding (N-H⋯O). The local reactivity descriptors analyses determine the reactive sites within molecule. The calculated first hyperpolarizability value (β0=23.83×10(-30) esu) of pyrrole dihydrazone shows its suitability for non-linear optical (NLO) response. The preliminary bioassay suggested that the PDBO exhibits relatively good antibacterial and fungicidal activity against Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Streptococcus pyogenes, Candida albicans, Aspergillus niger. The local reactivity descriptors--Fukui functions (fk+, fk-), local softnesses (sk+, sk-) and electrophilicity indices (ωk+, ωk-) analyses have been used to determine the reactive sites within molecule.

  2. Lysine pyrrolation is a naturally-occurring covalent modification involved in the production of DNA mimic proteins.

    PubMed

    Miyashita, Hiroaki; Chikazawa, Miho; Otaki, Natsuki; Hioki, Yusuke; Shimozu, Yuki; Nakashima, Fumie; Shibata, Takahiro; Hagihara, Yoshihisa; Maruyama, Shoichi; Matsumi, Noriyoshi; Uchida, Koji

    2014-06-18

    Covalent modification of proteins exerts significant effects on their chemical properties and has important functional and regulatory consequences. We now report the identification and verification of an electrically-active form of modified proteins recognized by a group of small molecules commonly used to interact with DNA. This previously unreported property of proteins was initially discovered when the γ-ketoaldehydes were identified as a source of the proteins stained by the DNA intercalators. Using 1,4-butanedial, the simplest γ-ketoaldehyde, we characterized the structural and chemical criteria governing the recognition of the modified proteins by the DNA intercalators and identified N(ε)-pyrrolelysine as a key adduct. Unexpectedly, the pyrrolation conferred an electronegativity and electronic properties on the proteins that potentially constitute an electrical mimic to the DNA. In addition, we found that the pyrrolated proteins indeed triggered an autoimmune response and that the production of specific antibodies against the pyrrolated proteins was accelerated in human systemic lupus erythematosus. These findings and the apparent high abundance of N(ε)-pyrrolelysine in vivo suggest that protein pyrrolation could be an endogenous source of DNA mimic proteins, providing a possible link connecting protein turnover and immune disorders.

  3. Synthesis of furo[3,2-b]pyrrole-5-carboxhydrazides and their Cu, Co and Ni complexes.

    PubMed

    Gašparová, Renata; Titiš, Ján; Kraic, Filip

    2012-01-01

    Carboxhydrazides 3 were synthesized by reaction of substituted furo[3,2-b]pyrrole-5-carboxhydrazides 1 with 4-oxo-4H-chromene-2-carboxaldehyde 2 in the presence of 3-methyl-benzenesulfonic acid in ethanol. Carboxhydrazides 3 were used as ligands for synthesis of Cu, Co, and Ni complexes 4.

  4. A Guided Inquiry Experiment for the Measurement of Activation Energies in the Biophysical Chemistry Laboratory: Decarboxylation of Pyrrole-2-Carboxylate

    ERIC Educational Resources Information Center

    Hutchinson, Kelly M.; Bretz, Stacey Lowery; Mettee, Howard D.; Smiley, Jeffrey A.

    2005-01-01

    A laboratory experiment for undergraduate biophysical chemistry is described, in which the acid concentration and temperature dependences of the decarboxylation of pyrrole-2-carboxylate are measured using a continuous ultraviolet (UV) spectrophotometric assay. Data collection and analysis are structured using principles of guided inquiry. Data…

  5. Synthesis of Furo[3,2-b]pyrrole-5-carboxhydrazides and Their Cu, CO and Ni Complexes

    PubMed Central

    Gašparová, Renata; Titiš, Ján; Kraic, Filip

    2012-01-01

    Carboxhydrazides 3 were synthesized by reaction of substituted furo[3,2-b]pyrrole-5-carboxhydrazides 1 with 4-oxo-4H-chromene-2-carboxaldehyde 2 in the presence of 3-methyl-benzenesulfonic acid in ethanol. Carboxhydrazides 3 were used as ligands for synthesis of Cu, Co, and Ni complexes 4. PMID:22593710

  6. Assessment of conformational, spectral, antimicrobial activity, chemical reactivity and NLO application of Pyrrole-2,5-dicarboxaldehyde bis(oxaloyldihydrazone)

    NASA Astrophysics Data System (ADS)

    Rawat, Poonam; Singh, R. N.

    2015-04-01

    An orange colored pyrrole dihydrazone: Pyrrole-2,5-dicarboxaldehyde bis(oxaloyldihydrazone) (PDBO) has been synthesized by reaction of oxalic acid dihydrazide with 2,5 diformyl-1H-pyrrole and has been characterized by spectroscopic analysis (1H, 13C NMR, UV-visible, FT-IR and DART Mass). The properties of the compound has been evaluated using B3LYP functional and 6-31G(d,p)/6-311+G(d,p) basis set. The symmetric (3319, 3320 cm-1) and asymmetric (3389, 3382 cm-1) stretching wave number confirm free NH2 groups in PDBO. NBO analysis shows, inter/intra molecular interactions within the molecule. Topological parameters have been analyzed by QTAIM theory and provide the existence of intramolecular hydrogen bonding (N-H⋯O). The local reactivity descriptors analyses determine the reactive sites within molecule. The calculated first hyperpolarizability value (β0 = 23.83 × 10-30 esu) of pyrrole dihydrazone shows its suitability for non-linear optical (NLO) response. The preliminary bioassay suggested that the PDBO exhibits relatively good antibacterial and fungicidal activity against Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Streptococcus pyogenes, Candida albicans, Aspergillus niger. The local reactivity descriptors - Fukui functions (fk+, fk-), local softnesses (sk+, sk-) and electrophilicity indices (ωk+, ωk-) analyses have been used to determine the reactive sites within molecule.

  7. Controlling bacterial behavior with indole-containing natural products and derivatives

    PubMed Central

    Melander, Roberta J.; Minvielle, Marine J.; Melander, Christian

    2014-01-01

    Indole has recently been implicated as an important small molecule signal utilized by many bacteria to coordinate various forms of behavior. Indole plays a role in numerous bacterial processes, including: biofilm formation and maintenance, virulence factor production, antibiotic resistance and persister cell formation. Intercepting indole-signaling pathways with appropriately designed small molecules provides a n opportunity to control unwanted bacterial behaviors, and is an attractive anti-virulence therapeutic strategy. In this review, we give an overview of the process controlled by indole signaling, and summarize current efforts to design indole-containing small molecules to intercept these pathways, and detail the synthetic efforts towards accessing indole derived bioactive small molecules. PMID:25267859

  8. Indole-Induced Activities of β-Lactamase and Efflux Pump Confer Ampicillin Resistance in Pseudomonas putida KT2440

    PubMed Central

    Kim, Jisun; Shin, Bora; Park, Chulwoo; Park, Woojun

    2017-01-01

    Indole, which is widespread in microbial communities, has received attention because of its effects on bacterial physiology. Pseudomonas putida and Pseudomonas aeruginosa can acquire ampicillin (Amp) resistance during growth on indole-Amp agar. Transcriptome, mutant, and inhibitor studies have suggested that Amp resistance induced by indole can be attributed to increased gene expression of ttgAB encoding two genes of RND-type multidrug efflux operons and an ampC encoding β-lactamase. Expression, enzyme activities, and mutational analyses indicated that AmpC β-lactamase is important for acquiring Amp resistance of P. putida in the presence of indole. Here, we show, for the first time, that volatile indole increased Amp-resistant cells. Consistent with results of the volatile indole assay, a low concentration of indole in liquid culture promoted growth initially, but led to mutagenesis after indole was depleted, which could not be observed at high indole concentrations. Interestingly, ttgAB and ampC gene expression levels correlate with the concentration of indole, which might explain the low number of Amp-mutated cells in high indole concentrations. The expression levels of genes involved in mutagenesis, namely rpoS, recA, and mutS, were also modulated by indole. Our data indicates that indole reduces Amp-induced heterogeneity by promoting expression of TtgABC or MexAB-OprM efflux pumps and the indole-induced β-lactamase in P. putida and P. aeruginosa. PMID:28352264

  9. Photodissociation dynamics of pyrrole: evidence for mode specific dynamics from conical intersections.

    PubMed

    Wei, J; Riedel, J; Kuczmann, A; Renth, F; Temps, F

    2004-01-01

    The H and D atom elimination mechanisms in the photodissociation of jet cooled pyrrole and pyrrole-d1 have been studied by photofragment velocity map imaging. The molecules were excited to the 1 1A2 (pi sigma*) state at lambda = 243 nm and to the 1 1B2 (pi pi*) state at lambda = 217 nm. H/D atoms were detected by (2 + 1) resonance enhanced multiphoton ionization (REMPI) at lambda = 243 nm. The analysis of the images and the resulting translational energy distributions from the 1 1A2 state demonstrates the existence of two decay pathways, fast mode-specific cleavage of the NH bond in the excited state (channel A) and internal conversion (IC) to the electronic ground state (S0) followed by unimolecular decomposition of the vibrationally hot S0 molecules (channel B). The angular distributions of the H/D atoms from the direct dissociation in the excited state are strongly anisotropic, whereas the decay of the S0 molecules leads to spatially isotropic distributions. The results at lambda = 217 nm indicate that the 1 1B2 state undergoes an ultrafast radiationless transition to 1 1A2 followed by the abovementioned direct mode-specific NH bond fission on the 1 1A2 potential energy surface (channel A') or conversion to S0 and subsequent unimolecular decomposition (channel B'). The latter pathway may also be initiated by a direct relaxation from 1 1B2 to S0. The anisotropy parameter of beta approximately -1 for the direct NH bond fission at lambda = 217 nm is in accordance with the expectations for a perpendicular electronic excitation and a dissociation lifetime that is short compared to the rotational period of the molecules. The fast decay dynamics of both excited electronic states can be rationalized with reference to the theoretically predicted conical intersections between the pi pi*, pi sigma*, and S0 potential energy surfaces and the antibonding nature of the pi sigma* potential energy surface with respect to the NH bond [A. L. Sobolewski, W. Domcke. C. Dedonder

  10. ZrCl4-mediated regio- and chemoselective Friedel-Crafts acylation of indole.

    PubMed

    Guchhait, Sankar K; Kashyap, Maneesh; Kamble, Harshad

    2011-06-03

    An efficient method for regio- and chemoselective Friedel-Crafts acylation of indole using acyl chlorides in the presence of ZrCl(4) has been discovered. It minimizes/eliminates common competing reactions that occur due to high and multiatom-nucleophilic character of indole. In this method, a wide range of aroyl, heteroaroyl alkenoyl, and alkanoyl chlorides undergo smooth acylation with various indoles without NH protection and afford 3-acylindoles in good to high yields.

  11. Conductance and Geometry of Pyridine-Linked Single Molecule Junctions

    SciTech Connect

    Kamenetska, M.; Hybertsen, M.; Quek, S.Y.; Whalley, A.C.; Steigerwald, M.L.; Choi, H.J.; Louie, S.G.; Nuckolls, C.; Neaton, J.B.; Venkataraman, L.

    2010-05-19

    We have measured the conductance and characterized molecule-electrode binding geometries of four pyridine-terminated molecules by elongating and then compressing gold point contacts in a solution of molecules. We have found that all pyridine-terminated molecules exhibit bistable conductance signatures, signifying that the nature of the pyridine-gold bond allows two distinct conductance states that are accessed as the gold-molecule-gold junction is elongated. We have identified the low-conductance state as corresponding to a molecule fully stretched out between the gold electrodes, where the distance between contacts correlates with the length of the molecule; the high-conductance state is due to a molecule bound at an angle. For all molecules, we have found that the distribution of junction elongations in the low-conductance state is the same, while in the high-conductance state, the most likely elongation length increases linearly with molecule length. The results of first-principles conductance calculations for the four molecules in the low-conductance geometry agree well with the experimental results and show that the dominant conducting channel in the conjugated pyridine-linked molecules is through the {pi}* orbital.

  12. Investigations into the mechanisms of pyridine ring cleavage in vismodegib.

    PubMed

    Khojasteh, S Cyrus; Yue, Qin; Ma, Shuguang; Castanedo, Georgette; Chen, Jacob Z; Lyssikatos, Joseph; Mulder, Teresa; Takahashi, Ryan; Ly, Justin; Messick, Kirsten; Jia, Wei; Liu, Lichuan; Hop, Cornelis E C A; Wong, Harvey

    2014-03-01

    Vismodegib (Erivedge, GDC-0449) is a first-in-class, orally administered small-molecule Hedgehog pathway inhibitor that is approved for the treatment of advanced basal cell carcinoma. Previously, we reported results from preclinical and clinical radiolabeled mass balance studies in which we determined that metabolism is the main route of vismodegib elimination. The metabolites of vismodegib are primarily the result of oxidation followed by glucuronidation. The focus of the current work is to probe the mechanisms of formation of three pyridine ring-cleaved metabolites of vismodegib, mainly M9, M13, and M18, using in vitro, ex vivo liver perfusion and in vivo rat studies. The use of stable-labeled ((13)C2,(15)N)vismodegib on the pyridine ring exhibited that the loss of carbon observed in both M9 and M13 was from the C-6 position of pyridine. Interestingly, the source of the nitrogen atom in the amide of M9 was from the pyridine. Evidence for the formation of aldehyde intermediates was observed using trapping agents as well as (18)O-water. Finally, we conclude that cytochrome P450 is involved in the formation of M9, M13, and M18 and that M3 (the major mono-oxidative metabolite) is not the precursor for the formation of these cleaved products; rather, M18 is the primary cleaved metabolite.

  13. Multidimensional Large Amplitude Dynamics in the Pyridine-Water Complex.

    PubMed

    Mackenzie, Rebecca B; Dewberry, Christopher T; Cornelius, Ryan D; Smith, C J; Leopold, Kenneth R

    2017-02-02

    Aqueous pyridine plays an important role in a variety of catalytic processes aimed at harnessing solar energy. In this work, the pyridine-water interaction is studied by microwave spectroscopy and density functional theory calculations. Water forms a hydrogen bond to the nitrogen with the oxygen tilted slightly toward either of the ortho-hydrogens of the pyridine, and a tunneling motion involving in-plane rocking of the water interconverts the resulting equivalent structures. A pair of tunneling states with severely perturbed rotational spectra is identified and their energy separation, ΔE, is inferred from the perturbations and confirmed by direct measurement. Curiously, values of ΔE are 10404.45 and 13566.94 MHz for the H2O and D2O complexes, respectively, revealing an inverted isotope effect upon deuteration. Small splittings in some transitions suggest an additional internal motion making this complex an interesting challenge for theoretical treatments of large amplitude motion. The results underscore the significant effect of the ortho-hydrogens on the intermolecular interaction of pyridine.

  14. Ethynyl-linked (pyreno)pyrrole-naphthyridine and aniline-naphthyridine molecules as fluorescent sensors of guanine via multiple hydrogen bondings.

    PubMed

    Lu, Shao-Hung; Selvi, Srinivasan; Fang, Jim-Min

    2007-01-05

    New fluorescent molecular sensors for 9-alkylguanines were constructed by conjugation of 2-acetamido-1,8-naphthyridine with N-Boc-pyrrole, N-Boc-pyreno[2,1-b]pyrrole, or acetanilide moieties via an ethynyl bridge. In combination with the triple hydrogen-bonding motif of 2-acetamidonaphthyridine toward alkylguanine, an additional binding site was provided by the substituent properly located on the pyrrole or aniline ring to enhance the affinity of these receptor molecules. Besides the ESI-MS analyses, the binding events were readily monitored by the absorption and fluorescence changes in the visible region.

  15. Modelling flavoenzymatic charge transfer events: development of catalytic indole deuteration strategies.

    PubMed

    Murray, Alexander T; Challinor, Jonathan D; Gulácsy, Christina E; Lujan, Cristina; Hatcher, Lauren E; Pudney, Christopher R; Raithby, Paul R; John, Matthew P; Carbery, David R

    2016-04-12

    The formation and chemistry of flavin-indole charge transfer (CT) complexes has been studied using a model cationic flavin. The ability to form a CT complex is sensitive to indole structure as gauged by spectroscopic, kinetics and crystallographic studies. Single crystals of sufficient quality of a flavin-indole CT complex, suitable for X-ray diffraction, have been grown, allowing solid-state structural analysis. When CT complex formation is conducted in d4-methanol, an efficient and synthetically useful C-3 indole deuteration is observed.

  16. Indole Alkaloids from the Sea Anemone Heteractis aurora and Homarine from Octopus cyanea.

    PubMed

    Shaker, Kamel H; Göhl, Matthias; Müller, Tobias; Seifert, Karlheinz

    2015-11-01

    The two new indole alkaloids 2-amino-1,5-dihydro-5-(1H-indol-3-ylmethyl)-4H-imidazol-4-one (1), 2-amino-5-[(6-bromo-1H-indol-3-yl)methyl]-3,5-dihydro-3-methyl-4H-imidazol-4-one (2), and auramine (3) have been isolated from the sea anemone Heteractis aurora. Both indole alkaloids were synthesized for the confirmation of the structures. Homarine (4), along with uracil (5), hypoxanthine (6), and inosine (7) have been obtained from Octopus cyanea.

  17. Indole is an essential herbivore-induced volatile priming signal in maize

    PubMed Central

    Erb, Matthias; Veyrat, Nathalie; Robert, Christelle A. M.; Xu, Hao; Frey, Monika; Ton, Jurriaan; Turlings, Ted C. J.

    2015-01-01

    Herbivore-induced volatile organic compounds prime non-attacked plant tissues to respond more strongly to subsequent attacks. However, the key volatiles that trigger this primed state remain largely unidentified. In maize, the release of the aromatic compound indole is herbivore-specific and occurs earlier than other induced responses. We therefore hypothesized that indole may be involved in airborne priming. Using indole-deficient mutants and synthetic indole dispensers, we show that herbivore-induced indole enhances the induction of defensive volatiles in neighbouring maize plants in a species-specific manner. Furthermore, the release of indole is essential for priming of mono- and homoterpenes in systemic leaves of attacked plants. Indole exposure markedly increases the herbivore-induced production of the stress hormones jasmonate-isoleucine conjugate and abscisic acid, which represents a likely mechanism for indole-dependent priming. These results demonstrate that indole functions as a rapid and potent aerial priming agent that prepares systemic tissues and neighbouring plants for incoming attacks. PMID:25683900

  18. Substituent effect in the photochromism of two isomeric asymmetric diarylethenes having pyrrole and thiophene units

    NASA Astrophysics Data System (ADS)

    Wang, Renjie; Zhang, Xiaoxia; Pu, Shouzhi; Liu, Gang; Dai, Yanfeng

    2017-02-01

    Two new asymmetric isomeric diarylethenes having pyrrole and thiophene units have been synthesized by one-pot reaction and characterized by single crystal X-ray diffraction analysis. The two prepared diarylethenes had disparate crystal structures, and they exhibited distinctly different photochromic behavior, both in solution and in the solid state. Their photochromism, fatigue resistance, and fluorescence were investigated systematically. The methyl group at the reactive carbon atom could significantly enhance the quantum yield of cyclization step and decrease the quantum yield of cycloreversion step, whereas a cyano group at the same position could notably suppress the photocyclization reaction and promote the photocycloreversion reaction. The results indicated that the substituent at the reactive carbon atom could readily modulate the optoelectronic and physical properties for these diarylethenes.

  19. Colorimetric chemosensor for multi-signaling detection of metal ions using pyrrole based Schiff bases.

    PubMed

    Udhayakumari, Duraisamy; Velmathi, Sivan

    2014-03-25

    Pyrrole based Schiff bases act as a highly sensitive probe for metal ions in aqueous medium. Both receptors R1 and R2 are sensitive towards Fe(3+), Cu(2+), Hg(2+) and Cr(3+) among the other metal ions. The sensing ability of the receptors are investigated via colorimetric, optical and emission spectroscopic studies. The binding stoichiometries of R1 and R2 with metal ions have been determined as 2:1 by using Job's plot. The colorimetric receptors exhibited high sensitivity with a low detection limit of μM levels. In the presence of metal ions both receptors shows fluorescence quenching. This might be due to the photo induced electron transfer mechanism. The quenching constant was further determined using Stern-Volmer plot. Copyright © 2013 Elsevier B.V. All rights reserved.

  20. Crystal structure of 1-benzyl-4-formyl-1H-pyrrole-3-carb­oxamide

    PubMed Central

    Zhong, Qi-Di; Hu, Sheng-Quan; Yan, Hong

    2016-01-01

    In the title compound, C13H12N2O2 (I), the mean planes of the pyrrole and benzyl rings are approximately perpendicular, forming a dihedral angle of 87.07 (4) °. There is an intra­molecular N—H⋯O hydrogen bond forming an S(7) ring motif. In the crystal, mol­ecules are linked via a pair of N—H⋯O hydrogen bonds forming inversion dimers. C—H⋯O hydrogen bonds link the dimers into chains along direction [10-1]. The chains are further linked by weak C—H⋯π inter­actions forming layers parallel to the ac plane. PMID:26958371

  1. Supramolecular biosensors based on electropolymerised pyrrole-cyclodextrin modified surfaces for antibody detection.

    PubMed

    Wajs, Ewelina; Fernández, Núria; Fragoso, Alex

    2016-06-07

    The self-assembly of an adamantane-appended polymer bearing an antigen fragment on a polypyrrole-cyclodextrin modified surface provides a highly sensitive immunosensor with low limits of detection for celiac disease related targets. The pyrrole-carboxylic acid films were formed on the surface of gold electrodes by electropolymerisation and followed by covalent attachment of cyclodextrin units. Surface plasmon resonance measurements confirmed the role of the host/guest interactions between adamantane moieties and β-cyclodextrin hosts in the formation of the supramolecular sensor interface. Furthermore, this novel electrochemical supramolecular platform was effective in the amperometric detection of anti-gliadin antibodies in spiked serum samples with very good signal recovery.

  2. An iterative nonribosomal peptide synthetase assembles the pyrrole-amide antibiotic congocidine in Streptomyces ambofaciens.

    PubMed

    Juguet, Maud; Lautru, Sylvie; Francou, François-Xavier; Nezbedová, Sárka; Leblond, Pierre; Gondry, Muriel; Pernodet, Jean-Luc

    2009-04-24

    Congocidine (netropsin) is a pyrrole-amide (oligopyrrole, oligopeptide) antibiotic produced by Streptomyces ambofaciens. We have identified, in the right terminal region of the S. ambofaciens chromosome, the gene cluster that directs congocidine biosynthesis. Heterologous expression of the cluster and in-frame deletions of 8 of the 22 genes confirm the involvement of this cluster in congocidine biosynthesis. Nine genes can be assigned specific functions in regulation, resistance, or congocidine assembly. In contrast, the biosynthetic origin of the precursors cannot be easily inferred from in silico analyses. Congocidine is assembled by a nonribosomal peptide synthetase (NRPS) constituted of a free-standing module and several single-domain proteins encoded by four genes. The iterative use of its unique adenylation domain, the utilization of guanidinoacetyl-CoA as a substrate by a condensation domain, and the control of 4-aminopyrrole-2-carboxylate polymerization constitute the most original features of this NRPS.

  3. Novel composite materials synthesized by the high-temperature interaction of pyrrole with layered oxide matrices

    NASA Astrophysics Data System (ADS)

    Pavel, Alexandru Cezar

    The initial goal of the research presented herein was to develop the very first synthetic metal---high-temperature superconductor ceramic composite material, in the specific form of a polypyrrole---Bi2Sr2CaCu 2O8+delta nanocomposite. In the course of scientific investigation, this scope was broadened to encompass structurally and compositionally similar layered bismuthates and simpler layered oxides. The latter substrates were prepared through novel experimental procedures that enhanced the chance of yielding nanostructured morphologies. The designed novel synthesis approaches yielded a harvest of interesting results that may be further developed upon their dissemination in the scientific community. High-temperature interaction of pyrrole with molybdenum trioxide substrates with different crystalline phases and morphologies led to the formation of the first members of a new class of heterogeneous microcomposites characterized by incomplete occupancy by the metal oxide core of the volume encapsulated by the rigid, amorphous permeable polymeric membrane that reproduces the volume of the initial grain of precursor substrate. The method may be applied for various heterogeneous catalyst substrates for the precise determination of the catalytically active crystallographic planes. In a different project, room-temperature, templateless impregnation of molybdenum trioxide substrates with different crystalline phases and morphologies by a large excess of silver (I) cations led to the formation of 1-D nanostructured novel Ag-Mo-O ternary phase in what may be the simplest experimental procedure available to date that has yielded a 1-D nanostructure, regardless the nature of the constituent material. Interaction of this novel ternary phase with pyrrole vapors at high reaction temperatures led to heterogeneous nanostructured composites that exhibited a silver nanorod core. Nanoscrolls of vanadium pentoxide xerogel were synthesized through a novel, facile reflux-based method that

  4. Synthesis and pharmacological characterization of bicyclic triple reuptake inhibitor 3-aryl octahydrocyclopenta[c]pyrrole analogues.

    PubMed

    Shao, Liming; Hewitt, Michael C; Malcolm, Scott C; Wang, Fengjiang; Ma, Jianguo; Campbell, Una C; Spicer, Nancy A; Engel, Sharon R; Hardy, Larry W; Jiang, Zhi-Dong; Schreiber, Rudy; Spear, Kerry L; Varney, Mark A

    2011-08-11

    The present work expands the chemical space known to offer potent inhibition of the serotonin transporter (SERT), norepinephrine transporter (NET), and dopamine transporter (DAT) and discloses novel bicyclic octahydrocyclopenta[c]pyrrole and octahydro-1H-isoindole scaffolds as potent triple reuptake inhibitors (TRIs) for the potential treatment of depression. Optimized compounds 22a (SERT, NET, DAT, IC(50) = 20, 109, 430 nM), 23a (SERT, NET, DAT, IC(50) = 29, 85, 168 nM), and 26a (SERT, NET, DAT, IC(50) = 53, 150, 140 nM) were highly brain penetrant, active in vivo in the mouse tail suspension test at 10 and 30 mpk PO, and were not generally motor stimulants at doses ranging from 1 to 30 mpk PO. Moderate in vitro cytochrome P450 (CYP) and potassium ion channel Kv11.1 (hERG) inhibition were uncovered as potential liabilities for the chemical series.

  5. Electrochemical nitrate biosensor based on poly(pyrrole-viologen) film-nitrate reductase-clay composite.

    PubMed

    Cosnier, S; Da Silva, S; Shan, D; Gorgy, K

    2008-11-01

    The immobilization of nitrate reductase (NR) was performed by entrapment in a laponite clay gel and cross-linking by glutaraldehyde. In presence of nitrate and methyl viologen, a catalytic current appeared at -0.60 V illustrating the enzymatic reduction of nitrate into nitrite via the reduced form of the freely diffusing methyl viologen. The electropolymerization of a water-soluble pyrrole viologen derivative within the interlamellar spaces and channels of the host clay matrix successfully carried out the electrical wiring of the entrapped NR. Rotating disk measurements led to the determination of kinetic constants, namely k(2)=10.7 s(-1) and K(M)=7 microM. These parameters reflect the efficiency of the electro-enzymatic reduction of nitrate and the substrate affinity for the immobilized enzyme.

  6. Depopulation of Single-Phthalocyanine Molecular Orbitals upon Pyrrolic-Hydrogen Abstraction on Graphene.

    PubMed

    Néel, Nicolas; Lattelais, Marie; Bocquet, Marie-Laure; Kröger, Jörg

    2016-02-23

    Single-molecule chemistry with a scanning tunneling microscope has preponderantly been performed on metal surfaces. The molecule-metal hybridization, however, is often detrimental to genuine molecular properties and obscures their changes upon chemical reactions. We used graphene on Ir(111) to reduce the coupling between Ir(111) and adsorbed phthalocyanine molecules. By local electron injection from the tip of a scanning tunneling microscope the two pyrrolic H atoms were removed from single phthalocyanines. The detachment of the H atom pair induced a strong modification of the molecular electronic structure, albeit with no change in the adsorption geometry. Spectra and maps of the differential conductance combined with density functional calculations unveiled the entire depopulation of the highest occupied molecular orbital upon H abstraction. Occupied π states of intact molecules are proposed to be emptied via intramolecular electron transfer to dangling σ states of H-free N atoms.

  7. Low-energy electron scattering from the aza-derivatives of pyrrole, furan, and thiophene

    NASA Astrophysics Data System (ADS)

    Kossoski, F.; Bettega, M. H. F.

    2013-06-01

    We report elastic integral and differential cross sections for electron scattering from the aza-derivatives of pyrrole, furan, and thiophene, namely, pyrazole, imidazole, isoxazole, oxazole, isothiazole, and thiazole. The calculations were performed within the Schwinger multichannel method with pseudopotentials, with inclusion of static, exchange, and polarization interactions, for energies up to 10 eV. We found two π* shape resonances and a high-lying σ* shape resonance in each system. A sharp low-energy σ* resonance was also identified in isothiazole and thiazole. Pyrazole and imidazole presented yet a broad low-lying σ* resonance. The positions of the resonances agree very well with existing experimental results. We discuss the similarities and differences among the resonances of these compounds.

  8. Chiral pyridin-3-ones and pyridines: syntheses of enantiopure 2,4-disubstituted 6-hydroxy-1,6-dihydro-2H-pyridin-3-ones, 2,3-disubstituted 4-iodopyridines, and enantiopure 2,3-disubstituted 4-pyridinemethanols.

    PubMed

    Husain, Irfan; Saquib, Mohammad; Bajpai, Vikas; Kumar, Brijesh; Shaw, Arun K

    2011-11-04

    The development of an innovative method to access enantiopure 2,4-disubstituted 6-hydroxy-1,6-dihydro-2H-pyridin-3-ones starting from D-glucal via the aza-Achmatowicz transformation has been described. These highly functionalized pyridin-3-ones have been utilized for the synthesis of contiguously substituted pyridines through a rapid and efficient Et(3)N/Ac(2)O promoted cyclo-elimination, aromatization cascade, allowing the facile assembly of important pyridine-based building blocks like 2-substituted 3-acetoxy-4-iodopyridines and enantiopure 2-substituted 3-acetoxy-4-pyridinemethanols possessing benzylic stereogenic centers, whose synthesis otherwise would be tedious. The utilization of commercially available sugars as starting materials, mild reaction conditions, catalytic transfer hydrogen (CTH) of α-furfuryl azide derivatives, transfer of chiral aryl/alkyl methanols from enulosides to pyridin-3-ones and pyridines, high yields, and short reaction times are key features of this method. The utility of the method has been further exemplified by demonstrating the usage of the 2-substituted 3-acetoxy-4-iodopyridine for the construction of biologically significant molecules like 2,7-disubstituted furo[2,3-c]pyridines and 7,7'-disubstituted 2,2'-bifuro[2,3-c]pyridines.

  9. Cross-linked polyvinyl pyridine coated glass particle catalyst support and aqueous composition or polyvinyl pyridine adducted microspheres

    NASA Technical Reports Server (NTRS)

    Rembaum, Alan (Inventor); Gupta, Amitava (Inventor); Volksen, Willi (Inventor)

    1981-01-01

    Microspheres are produced by cobalt gamma radiation initiated polymerization of a dilute aqueous vinyl pyridine solution. Addition of cross-linking agent provides higher surface area beads. Addition of monomers such as hydroxyethylmethacrylate acrylamide or methacrylamide increases hydrophilic properties and surface area of the beads. High surface area catalytic supports are formed in the presence of controlled pore glass substrate.

  10. Targeting a DNA binding motif of the EVI1 protein by a pyrrole-imidazole polyamide.

    PubMed

    Zhang, Yi; Sicot, Géraldine; Cui, Xiaohui; Vogel, Marion; Wuertzer, Charles A; Lezon-Geyda, Kimberly; Wheeler, John; Harki, Daniel A; Muzikar, Katy A; Stolper, Daniel A; Dervan, Peter B; Perkins, Archibald S

    2011-12-06

    The zinc finger protein EVI1 is causally associated with acute myeloid leukemogenesis, and inhibition of its function with a small molecule therapeutic may provide effective therapy for EVI1-expressing leukemias. In this paper we describe the development of a pyrrole-imidazole polyamide to specifically block EVI1 binding to DNA. We first identify essential domains for leukemogenesis through structure-function studies on both EVI1 and the t(3;21)(q26;q22)-derived RUNX1-MDS1-EVI1 (RME) protein, which revealed that DNA binding to the cognate motif GACAAGATA via the first of two zinc finger domains (ZF1, encompassing fingers 1-7) is essential transforming activity. To inhibit DNA binding via ZF1, we synthesized a pyrrole-imidazole polyamide 1, designed to bind to a subsite within the GACAAGATA motif and thereby block EVI1 binding. DNase I footprinting and electromobility shift assays revealed a specific and high affinity interaction between polyamide 1 and the GACAAGATA motif. In an in vivo CAT reporter assay using NIH-3T3-derived cell line with a chromosome-embedded tet-inducible EVI1-VP16 as well as an EVI1-responsive reporter, polyamide 1 completely blocked EVI1-responsive reporter activity. Growth of a leukemic cell line bearing overexpressed EVI1 was also inhibited by treatment with polyamide 1, while a control cell line lacking EVI1 was not. Finally, colony formation by RME was attenuated by polyamide 1 in a serial replating assay. These studies provide evidence that a cell permeable small molecule may effectively block the activity of a leukemogenic transcription factor and provide a valuable tool to dissect critical functions of EVI1 in leukemogenesis.

  11. In vitro rescue of genital strains of Chlamydia trachomatis from interferon-γ and tryptophan depletion with indole-positive, but not indole-negative Prevotella spp.

    PubMed

    Ziklo, Noa; Huston, Wilhelmina M; Taing, Kuong; Katouli, Mohammad; Timms, Peter

    2016-12-03

    The natural course of sexually transmitted infections caused by Chlamydia trachomatis varies between individuals. In addition to parasite and host effects, the vaginal microbiota might play a key role in the outcome of C. trachomatis infections. Interferon-gamma (IFN-γ), known for its anti-chlamydial properties, activates the expression of indoleamine 2,3-dioxygenase (IDO1) in epithelial cells, an enzyme that catabolizes the amino acid L- tryptophan into N-formylkynurenine, depleting the host cell's pool of tryptophan. Although C. trachomatis is a tryptophan auxotroph, urogenital strains (but not ocular strains) have been shown in vitro to have the ability to produce tryptophan from indole using the tryptophan synthase (trpBA) gene. It has been suggested that indole producing bacteria from the vaginal microbiota could influence the outcome of Chlamydia infection. We used two in vitro models (treatment with IFN-γ or direct limitation of tryptophan), to study the effects of direct rescue by the addition of exogenous indole, or by the addition of culture supernatant from indole-positive versus indole-negative Prevotella strains, on the growth and infectivity of C. trachomatis. We found that only supernatants from the indole-positive strains, P. intermedia and P. nigrescens, were able to rescue tryptophan-starved C. trachomatis. In addition, we analyzed vaginal secretion samples to determine physiological indole concentrations. In spite of the complexity of vaginal secretions, we demonstrated that for some vaginal specimens with higher indole levels, there was a link to higher recovery of the Chlamydia under tryptophan-starved conditions, lending preliminary support to the critical role of the IFN-γ-tryptophan-indole axis in vivo. Our data provide evidence for the ability of both exogenous indole as well as supernatant from indole producing bacteria such as Prevotella, to rescue genital C. trachomatis from tryptophan starvation. This adds weight to the hypothesis

  12. Gastroprotective mechanisms of indole alkaloids from Himatanthus lancifolius.

    PubMed

    Baggio, Cristiane Hatsuko; De Martini Otofuji, Glaucia; de Souza, Wesley Mauricio; de Moraes Santos, Cid Aimbiré; Torres, Luce Maria Brandao; Rieck, Lia; de Andrade Marques, Maria Consuelo; Mesia-Vela, Sonia

    2005-08-01

    The indole alkaloids mixture (AlkF) obtained from the barks of Himatanthus lancifolius (Muell. Arg.) Woodson was evaluated for gastroprotective properties in rodents. The AlkF potently protected rats from experimentally induced gastric lesions by ethanol (ED (50) = 30 mg/kg, p. o.) and reduced gastric acid hypersecretion induced by pylorus ligature (ED (50) = 82 mg/kg, i. d.). Protective effects of the AlkF in the ethanol and hypersecretion models included increase of GSH levels of gastric mucosa indicating activation of GSH-dependent cytoprotective mechanisms. Also, an increase of the antioxidant capacity as measured through glutathione S-transferase activity was observed in the hypersecretory but not in the ulcerative model. Furthermore, the amount of nitric oxide derivatives (NO (3) + NO (2)) in the forestomach was increased while the amount released into the gastric juice during pylorus ligature was decreased by the AlkF suggesting an alteration of NO-related mechanisms. Reduction of gastric acid hypersecretion induced by pylorus ligature seems to correlate with the blockade of H (+),K (+)-ATPase activity as determined in vitro by the capacity of the AlkF mix to decrease the hydrolysis of ATP by the ATPase isolated from dog gastric mucosa (EC (50) = 212 microg/mL). Cholinergic mechanisms can be excluded since intestinal transit was not modified with doses up to 100 mg/kg ( p. o.). GC-MS investigation of components of the AlkF resulted in the identification of 3 main indole alkaloids, uleine (53 %), its isomer (13 %), demethoxyaspidormine (23.8 %) and traces of at least other five alkaloids. Collectively, the results show the novel gastroprotective properties of the indole AlkF of H. lancifolius through a variety of mechanisms.

  13. Indole RSK inhibitors. Part 1: discovery and initial SAR.

    PubMed

    Boyer, Stephen J; Burke, Jennifer; Guo, Xin; Kirrane, Thomas M; Snow, Roger J; Zhang, Yunlong; Sarko, Chris; Soleymanzadeh, Lida; Swinamer, Alan; Westbrook, John; Dicapua, Frank; Padyana, Anil; Cogan, Derek; Gao, Amy; Xiong, Zhaoming; Madwed, Jeffrey B; Kashem, Mohammed; Kugler, Stanley; O'Neill, Margaret M

    2012-01-01

    A series of inhibitors for the 90 kDa ribosomal S6 kinase (RSK) based on an 1-oxo-2,3,4,5-tetrahydro-1H-[1,4]diazepino[1,2-a]indole-8-carboxamide scaffold were identified through high throughput screening. An RSK crystal structure and exploratory SAR were used to define the series pharmacophore. Compounds with good cell potency, such as compounds 43, 44, and 55 were identified, and form the basis for subsequent kinase selectivity optimization. Copyright © 2011 Elsevier Ltd. All rights reserved.

  14. Asymmetric Total Synthesis of the Indole Diterpene Alkaloid Paspaline

    PubMed Central

    Sharpe, Robert J.; Johnson, Jeffrey S.

    2015-01-01

    An enantioselective synthesis of the indole diterpenoid natural product paspaline is disclosed. Critical to this approach was the implementation of stereoselective desymmetrization reactions to assemble key stereocenters of the molecule. The design and execution of these tactics are described in detail, and a thorough analysis of observed outcomes is presented, ultimately providing the title compound in high stereopurity. This synthesis provides a novel template for preparing key stereocenters in this family of molecules, and the reactions developed en route to paspaline present a series of new synthetic disconnections in preparing steroidal natural products. PMID:26398568

  15. Indole alkaloids from the leaves of Philippine Alstonia scholaris.

    PubMed

    Macabeo, Allan Patrick G; Krohn, Karsten; Gehle, Dietmar; Read, Roger W; Brophy, Joseph J; Cordell, Geoffrey A; Franzblau, Scott G; Aguinaldo, Alicia M

    2005-05-01

    The first seco-uleine alkaloids, manilamine (1) (18-hydroxy-19,20-dehydro-7,21-seco-uleine) and N4-methyl angustilobine B (2), were isolated from the (pH 5) alkaloid extract of Philippine Alstonia scholaris leaves together with the known indole alkaloids 19,20-(E)-vallesamine (3), angustilobine B N4-oxide (4), 20(S)-tubotaiwine (5), and 6,7-seco-angustilobine B (6). The structure of the alkaloids was established from MS and NMR experiments.

  16. Development of indole-3-propionic acid (OXIGON) for Alzheimer's disease.

    PubMed

    Bendheim, Paul E; Poeggeler, Burkhard; Neria, Eyal; Ziv, Vivi; Pappolla, Miguel A; Chain, Daniel G

    2002-01-01

    The accumulation of amyloid-beta and concomitant oxidative stress are major pathogenic events in Alzheimer's disease. Indole-3-propionic acid (IPA, OXIGON) is a potent anti-oxidant devoid of pro-oxidant activity. IPA has been demonstrated to be an inhibitor of beta-amyloid fibril formation and to be a potent neuroprotectant against a variety of oxidotoxins. This review will summarize the known properties of IPA and outline the rationale behind its selection as a potential disease-modifying therapy for Alzheimer's disease.

  17. Three new monoterpenoid indole alkaloids from Vinca major.

    PubMed

    Zhang, Zhi-Jun; Du, Ru-Nan; He, Juan; Wu, Xing-De; Li, Yan; Li, Rong-Tao; Zhao, Qin-Shi

    2016-01-01

    Three new monoterpenoid indole alkaloids, 19-hydroxyl-10-methoxy-19, 20-dihydrovinorine (1), 19-O-acetyl-10-methoxy-19, 20-dihydrovinorine (2), and 19, 21α-dihydroxyl-10-methoxy-19, 20-dihydrovinorine (3), along with five known analogues (4-8), were isolated from the whole plants of Vinca major. The new structures were elucidated by extensive NMR and MS analysis and comparison with known compounds. In addition, compounds 1-3 were evaluated for their cytotoxicities against five human cancer cell lines.

  18. Indole alkaloids with new skeleton activating neural stem cells.

    PubMed

    Yang, Xing-Wei; Yang, Cui-Ping; Jiang, Li-Ping; Qin, Xu-Jie; Liu, Ya-Ping; Shen, Qiu-Shuo; Chen, Yong-Bin; Luo, Xiao-Dong

    2014-11-07

    Alstoscholarisines A-E (1-5), five unprecedented monoterpenoid indole alkaloids with 6/5/6/6/6 fused-bridge rings, were isolated from Alstonia scholaris. They promoted adult neuronal stem cells (NSCs) proliferation significantly, in which the most active one (1) functioned from a concentration of 0.1 μg/mL in a dosage-dependent manner. Furthermore, 1 enhanced NSC sphere formation and neurogenic fate commitment through activation of a Wnt signaling pathway and promoted NSC differentiation but did not affect proliferation of neuroblastoma cells.

  19. Biosynthesis and regulation of terpenoid indole alkaloids in Catharanthus roseus

    PubMed Central

    Zhu, Jianhua; Wang, Mingxuan; Wen, Wei; Yu, Rongmin

    2015-01-01

    Catharanthus roseus produces a wide range of terpenoid indole alkaloids (TIA). Many of them, such as vinblastine and vincristine, have significant bioactivity. They are valuable chemotherapy drugs used in combination with other drugs to treat lymphoma and leukemia. The TIA biosynthetic pathway has been investigated for many years, for scientific interest and for their potential in manufacturing applications, to fulfill the market demand. In this review, the progress and perspective of C. roseus TIA biosynthesis and its regulating enzymes are described. In addition, the culture condition, hormones, signaling molecules, precursor feeding on the accumulation of TIA, and gene expression are also evaluated and discussed. PMID:26009689

  20. Catalytic formal [2+2+1] synthesis of pyrroles from alkynes and diazenes via Ti(II)/Ti(IV) redox catalysis.

    PubMed

    Gilbert, Zachary W; Hue, Ryan J; Tonks, Ian A

    2016-01-01

    Pyrroles are structurally important heterocycles. However, the synthesis of polysubstituted pyrroles is often challenging. Here, we report a multicomponent, Ti-catalysed formal [2+2+1] reaction of alkynes and diazenes for the oxidative synthesis of penta- and trisubstituted pyrroles: a nitrenoid analogue to classical Pauson-Khand-type syntheses of cyclopentenones. Given the scarcity of early transition-metal redox catalysis, preliminary mechanistic studies are presented. Initial stoichiometric and kinetic studies indicate that the mechanism of this reaction proceeds through a formally Ti(II)/Ti(IV) redox catalytic cycle, in which an azatitanacyclobutene intermediate, resulting from [2+2] alkyne + Ti imido coupling, undergoes a second alkyne insertion followed by reductive elimination to yield pyrrole and a Ti(II) species. The key component for catalytic turnover is the reoxidation of the Ti(II) species to a Ti(IV) imido via the disproportionation of an η(2)-diazene-Ti(II) complex.

  1. Synthesis of copper and zinc 2-(pyridin-2-yl)imidazo[1,2-a]pyridine complexes and their potential anticancer activity.

    PubMed

    Dam, Jean; Ismail, Zeenat; Kurebwa, Taurai; Gangat, Nadia; Harmse, Leonie; Marques, Helder M; Lemmerer, Andreas; Bode, Moira L; de Koning, Charles B

    2017-01-27

    A small library of novel copper and zinc imidazo[1,2-a]pyridine complexes have been synthesized. Their structures were confirmed by X-ray diffraction crystallography and a selection of these compounds was tested against five cancer cell lines originating from breast cancer (MCF-7 and MDA-MB-231), leukemia (K562 and HL-60) and colorectal cancer (HT-29). The imidazo[1,2-a]pyridines and their zinc complexes showed poor anticancer activity, while the copper complexes were active against the cancer cell lines with IC50 values comparable to and lower than camptothecin. For example, copper 6-bromo-N-cyclohexyl-2-(pyridin-2-yl)imidazo[1,2-a]pyridin-3-amine acetate 21 had an IC50 value lower than 1 μM against the HT-29 cells. Fluorescence microscopy with acridine orange, Hoechst 33342 and ethidium bromide, used in a preliminary investigation to evaluate morphological changes showed that copper 6-bromo-N-cyclohexyl-2-(pyridin-2-yl)imidazo[1,2-a]pyridin-3-amine acetate 21 caused both apoptosis, necrosis and paraptosis in the MCF-7 and HL-60 cells. A select group of copper N-cyclohexyl-2-(pyridin-2-yl)imidazo[1,2-a]pyridin-3-amines (26, 27, 29 and 31) induced apoptosis, paraptosis and deformed nuclei in MCF-7 cells.

  2. A practical two-step synthesis of imidazo[1,2-a]pyridines from N-(prop-2-yn-1-yl)pyridin-2-amines.

    PubMed

    Sucunza, David; Samadi, Abdelouahid; Chioua, Mourad; Silva, Daniel B; Yunta, Cristina; Infantes, Lourdes; Carmo Carreiras, M; Soriano, Elena; Marco-Contelles, José

    2011-05-07

    The Sandmeyer reaction of differently C-2 substituted N-(prop-2-yn-1-ylamino)pyridines is an efficient, mild, new and practical method for the stereospecific synthesis of (E)-exo-halomethylene bicyclic pyridones bearing the imidazo[1,2-a]pyridine heterocyclic ring system.

  3. 2,2',5,5'-Tetra-methyl-1,1'-(hexane-1,6-di-yl)di-1H-pyrrole.

    PubMed

    Santos, Ana C; Ramos Silva, Manuela; Monsanto, Paula V; Matos Beja, Ana; Sobral, Abilio J F N

    2009-06-17

    The mol-ecule of the title compound, C(18)H(28)N(2), composed of two 2,5-dimethyl-pyrrole groups linked by a hexane chain, lies across a crystallographic inversion centre. The mean plane of the pyrrole ring is almost perpendicular to the mean plane of the central chain, making a dihedral angle of 89.09 (8)°. The crystal structure is stabilized by inter-molecular C-H⋯π inter-actions.

  4. Polymerization of Conducting Polymers Confined to Free Surfaces: A comparison of the Langmuir-Blodgett Polymerization of 3-Alkyl Pyrroles and 2- Alkyl Anilines

    DTIC Science & Technology

    1992-05-19

    Confined to Free Surfaces: A Comparison of the Langmuir-Blodgett Polymerization of 3- Alkyl Pyrroles and 2- Alkyl Anilines Submitted for Publication in...Surfaces: A Comparison of the Langmuir Blodgett Polymerizations of 3- alkyl pyrroles and 2- alkyl anilines R. S. Duran and H.C. Zhou Dept. of Chemistry...polymerization reactions in more detail and compare them. To do this, the polymerization reactions were run under two conditions. In the first case

  5. Vinyl azides derived from allenes: thermolysis leading to multisubstituted 1,4-pyrazines and Mn(III)-catalyzed photochemical reaction leading to pyrroles.

    PubMed

    Sajna, K V; Kumara Swamy, K C

    2012-10-05

    Thermolysis of phosphorus-based vinyl azides under solvent- and catalyst-free conditions furnished a new route for 1,4-pyrazines. A simple one-pot, Mn(III)-catalyzed photochemical route has been developed for multisubstituted pyrroles starting from allenes and 1,3-dicarbonyls via in situ-generated vinyl azides. The utility of new phosphorus-based pyrroles is also demonstrated in the Horner reaction. The structures of key products are unequivocally confirmed by X-ray crystallography.

  6. Organocatalytic asymmetric Henry reaction of 1H-pyrrole-2,3-diones with bifunctional amine-thiourea catalysts bearing multiple hydrogen-bond donors

    PubMed Central

    Zhang, Ming-Liang; Yue, Deng-Feng; Wang, Zhen-Hua; Luo, Yuan; Zhang, Xiao-Mei

    2016-01-01

    Summary For the first time, a catalytic asymmetric Henry reaction of 1H-pyrrole-2,3-diones was achieved with a chiral bifunctional amine-thiourea as a catalyst possessing multiple hydrogen-bond donors. With this developed method, a range of 3-hydroxy-3-nitromethyl-1H-pyrrol-2(3H)-ones bearing quaternary stereocenters were obtained in acceptable yield (up to 75%) and enantioselectivity (up to 73% ee). PMID:26977188

  7. Sigma and Pi Interactions of the Pyrrolic Ligand Sandwich-Like Lanthanide Phthalocyanines Determined from Magnetic Susceptibility and Ligand-Field Theory

    DTIC Science & Technology

    1990-06-25

    ACCESSION NO. 11, TITLE (include Security Classification) UNCLASSIFIED: Sigma and Pi Interactions of the Pyrro- lic Ligand Sandwich-Like Lanthanide ...4135007---05 TECHNICAL REPORT NO. 36 Sigma and Pi Interactions of the Pyrrolic Ligand Sandwich-Like Lanthanide Phthalocyanines Determined From Magnetic...Hill Chapel Hill, North Carolina 27599-3290 Sigma and Pi Interactions of the Pyrrolic Ligand Sandwich-Like Lanthanide Phthalocyanines Determined From

  8. Catalyst-controlled divergence in cycloisomerisation reactions of N-propargyl-N-vinyl sulfonamides: gold-catalysed synthesis of 2-sulfonylmethyl pyrroles and dihydropyridines.

    PubMed

    Undeela, Sridhar; Thadkapally, Srinivas; Nanubolu, Jagadeesh Babu; Singarapu, Kiran Kumar; Menon, Rajeev S

    2015-09-18

    Gold-catalysed, divergent synthesis of 2-sulfonylmethyl pyrroles and dihydropyridines from N-propargyl-N-vinyl sulfonamides has been achieved. Echavarren's gold(I) catalyst promoted the formation of pyrrole derivatives whereas the combination of PPh3AuCl and AgSbF6 afforded dihydropyridines. The aza-enyne precursors for the cycloisomerisation reaction were prepared by a base-mediated formal vinylic substitution reaction of 2-bromoallyl sulfones.

  9. Effect of the pasteurization process on the contents of ascorbigen, indole-3-carbinol, indole-3-acetonitrile, and 3,3'-diindolylmethane in fermented cabbage.

    PubMed

    Ciska, Ewa; Honke, Joanna

    2012-04-11

    The aim of the study was to investigate the effect of the pasteurization process on the content of ascorbigen, indole-3-carbinol, indole-3-acetonitrile, and 3,3'-diindolylmethane in fermented cabbage. Pasteurization was run at a temperature of 80 °C for 5-30 min. Significant changes were only observed in contents of ascorbigen and 3,3'-diindolylmethane. The total content of the compounds analyzed in cabbage pasteurized for 10-30 min was found to be decreased by ca. 20%, and the losses were due to thermal degradation of the predominating ascorbigen. Pasteurization was found not to exert any considerable effect on contents of indole-3-acetonitrile and indole-3-carbinol in cabbage nor did it affect contents of the compounds analyzed in juice.

  10. Rhodium(I)-Catalyzed Benzannulation of Heteroaryl Propargylic Esters: Synthesis of Indoles and Related Heterocycles.

    PubMed

    Li, Xiaoxun; Xie, Haibo; Fu, Xiaoning; Liu, Ji-Tian; Wang, Hao-Yuan; Xi, Bao-Min; Liu, Peng; Xu, Xiufang; Tang, Weiping

    2016-07-18

    A de novo synthesis of a benzene ring allows for the preparation of a diverse range of heterocycles including indoles, benzofurans, benzothiophenes, carbazoles, and dibenzofurans from simple heteroaryl propargylic esters using a unified carbonylative benzannulation strategy. Multiple substituents can be easily introduced to the C4-C7 positions of indoles and related heterocycles.

  11. Enantioselective Friedel-Crafts Alkylation Reactions of 3-Substituted Indoles with Electron-Deficient Alkenes.

    PubMed

    Weng, Jian-Quan; Fan, Ren-Jie; Deng, Qiao-Man; Liu, Ren-Rong; Gao, Jian-Rong; Jia, Yi-Xia

    2016-04-01

    Highly enantioselective Friedel-Crafts C2-alkylation reactions of 3-substituted indoles with α,β-unsaturated esters and nitroalkenes were developed using chiral Lewis acids as catalysts, which afforded chiral indole derivatives bearing C2-benzylic stereogenic centers in good to excellent yields (up to 99%) and enantioselectivities (up to 96% ee).

  12. Indole and its alkyl-substituted derivatives protect erythrocyte and DNA against radical-induced oxidation.

    PubMed

    Zhao, Feng; Liu, Zai-Qun

    2009-01-01

    The antioxidant properties of 1,2,3,4-tetra-hydrocarbazole, 6-methoxy-1,2,3,4-tetrahydrocar-bazole (MTC), 2,3-dimethylindole, 5-methoxy-2,3-dimethylindole, and indole were investigated in the case of hemolysis of human erythrocytes and oxidative damage of DNA induced by 2,2'-azobis(2-amidinopropane hydrochloride) (AAPH), respectively. The aim of this work was to explore the influence of methoxy, methyl, and cyclohexyl substituents on the antioxidant activities of indole derivatives. These indole derivatives were able to protect erythrocytes and DNA in a concentration-dependent manner. The alkyl-substituted indole can protect erythrocytes and DNA against AAPH-induced oxidation. Especially, the structural features of cyclohexyl and methoxy substituents made MTC the best antioxidant among the indole derivatives used herein. Finally, the interaction between these indole derivatives and 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonate) radical cation and 2,2'-diphenyl-1-picrylhydrazyl, respectively, provided direct evidence for these indole derivatives to scavenge radicals and emphasized the importance of electron-donating groups for the free radical-scavenging activity of indole derivatives. 2009 Wiley Periodicals, Inc.

  13. Stereoselective double Friedel-Crafts alkylation of indoles with divinyl ketones.

    PubMed

    Silvanus, Andrew C; Heffernan, Stephen J; Liptrot, David J; Kociok-Köhn, Gabriele; Andrews, Benjamin I; Carbery, David R

    2009-03-05

    A tandem double Friedel-Crafts reaction of indoles and nonsymmetrical divinyl ketones has been achieved. The tandem reaction forms complex [6-5-7]-tricyclic indoles in excellent yields. The reaction is completely regioselective and offers high levels of syn diastereoselectivity. The reaction is also seen to be sensitive to substrate structure and catalyst.

  14. Biotransformation of indole and its derivatives by a newly isolated Enterobacter sp. M9Z.

    PubMed

    Qu, Yuanyuan; Zhang, Zhaojing; Ma, Qiao; Shen, E; Shen, Wenli; Wang, Jingwei; Cong, Longchao; Li, Duanxing; Liu, Ziyan; Li, Huijie; Zhou, Jiti

    2015-04-01

    In this study, a novel bacterial strain M9Z with the ability of producing indigoids from indole and its derivatives was isolated from activated sludge and identified as Enterobacter sp. according to 16S ribosomal RNA (rRNA) sequence analysis. UV-vis spectrometry and high-performance liquid chromatography-mass spectrometry analysis indicated that the products produced from indole, 5-methylindole, 7-methylindole, and 5-methoxyindole were indigo with different substituent groups, and the possible biotransformation pathways of indole derivatives, i.e., indole(s)-cis-indole-2,3-dihydrodiol(s)-indoxyl(s)-indigoids, were proposed. The conditions of indole transformation and indigo biosynthesis by strain M9Z were optimized, and the maximal indigo yield (68.1 mg/L) was obtained when using 150 mg/L indole, 200 mg/L naphthalene, and 5 g/L yeast extract. The transformation rates of 5-methylindole, 7-methylindole, and 5-methoxyindole by strain M9Z were all close to 100 % under certain conditions, making strain M9Z an efficient indigoid producer. This is the first study of indole biotransformation and indigoid biosynthesis by genus Enterobacter.

  15. Nanoparticle Based Contrast Enhancement for Discriminating Indolent From Aggressive Prostate Cancer

    DTIC Science & Technology

    2016-06-01

    AWARD NUMBER: W81XWH-15-1-0102 TITLE: Nanoparticle -Based Contrast Enhancement for Discriminating Indolent From Aggressive Prostate Cancer...2016 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Nanoparticle -Based Contrast Enhancement for Discriminating Indolent From Aggressive Prostate Cancer 5b...followed through watchful waiting or active surveillance management. Specifically, we aim to image metallic and polymer nanoparticles as they

  16. Intermolecular decarboxylative direct C-3 arylation of indoles with benzoic acids.

    PubMed

    Cornella, Josep; Lu, Pengfei; Larrosa, Igor

    2009-12-03

    A palladium catalyzed C-H activation of indoles and a silver catalyzed decarboxylative C-C activation of ortho substituted benzoic acids are synergistically combined to synthesize indoles arylated exclusively in the C-3 position. This novel decarboxylative C-H arylation methodology is compatible with electron-donating and -withdrawing substituents in both coupling partners.

  17. Commensal Bacteria-Dependent Indole Production Enhances Epithelial Barrier Function in the Colon

    PubMed Central

    Shimada, Yosuke; Kinoshita, Makoto; Harada, Kazuo; Mizutani, Masafumi; Masahata, Kazunori; Kayama, Hisako; Takeda, Kiyoshi

    2013-01-01

    Microbiota have been shown to have a great influence on functions of intestinal epithelial cells (ECs). The role of indole as a quorum-sensing (QS) molecule mediating intercellular signals in bacteria has been well appreciated. However, it remains unknown whether indole has beneficial effects on maintaining intestinal barriers in vivo. In this study, we analyzed the effect of indole on ECs using a germ free (GF) mouse model. GF mice showed decreased expression of junctional complex molecules in colonic ECs. The feces of specific pathogen-free (SPF) mice contained a high amount of indole; however the amount was significantly decreased in the feces of GF mice by 27-fold. Oral administration of indole-containing capsules resulted in increased expression of both tight junction (TJ)- and adherens junction (AJ)-associated molecules in colonic ECs in GF mice. In accordance with the increased expression of these junctional complex molecules, GF mice given indole-containing capsules showed higher resistance to dextran sodium sulfate (DSS)-induced colitis. A similar protective effect of indole on DSS-induced epithelial damage was also observed in mice bred in SPF conditions. These findings highlight the beneficial role of indole in establishing an epithelial barrier in vivo. PMID:24278294

  18. Yuehchukene, a Novel Anti-implantation Indole Alkaloid from Murraya paniculata.

    PubMed

    Kong, Y C; Ng, K H; Wat, K H; Wong, A; Saxena, I F; Cheng, K F; But, P P; Chang, H T

    1985-08-01

    Yuehchukene, 11beta-(3'-indolyl-7,9alpha,9beta-trimethyl-5beta,8,9,10beta-tetrahydroindano-[2,3- B]indole, a novel dimeric indole alkaloid from the roots of MURRAY A PANICULATA has potent anti-implantation activity in rats at 3 mg/kg P. O. dosing on pregnancy day 2.

  19. Rhodium-Catalyzed NH-Indole-Directed C-H Carbonylation with Carbon Monoxide: Synthesis of 6H-Isoindolo[2,1-a]indol-6-ones.

    PubMed

    Huang, Qiufeng; Han, Qingshuai; Fu, Shurong; Yao, Zizhu; Su, Lv; Zhang, Xiaofeng; Lin, Shen; Xiang, Shengchang

    2016-12-16

    An efficient synthesis of 6H-isoindolo[2,1-a]indol-6-ones through rhodium-catalyzed NH-indole-directed C-H carbonylation of 2-arylindoles with carbon monoxide has been developed. Preliminary mechanistic studies revealed that this reaction proceeds via N-H bond cleavage and subsequent C-H bond cleavage. Reaction monitoring via ESI-MS was used to support the formation of five-membered rhodacycle species in the catalytic cycle.

  20. 5-Meth-oxy-1-[(5-meth-oxy-1H-indol-2-yl)meth-yl]-1H-indole.

    PubMed

    Attia, Mohamed I; El-Brollosy, Nasser R; Ghabbour, Hazem A; Arshad, Suhana; Fun, Hoong-Kun

    2012-04-01

    In the title compound, C(19)H(18)N(2)O(2), the two indole ring systems are essentially planar [maximum deviation = 0.015 (2) Å in both indole ring systems] and make a dihedral angle of 72.17 (7)° with each other. In the crystal, the mol-ecules are linked into a zigzag chain along the a axis via N-H⋯O hydrogen bonds.

  1. Systemic endotoxin levels in chronic indolent periodontal infections

    PubMed Central

    Ebersole, J. L.; Stevens, J.; Steffen, M. J.; Dawson, D.; Novak, M. J.

    2014-01-01

    Background and Objective: Periodontal disease has been linked with an increased risk of various systemic diseases. A plausible biologic explanation for this link includes the opportunity for oral pathogens to translocate to the circulation as a result of breakdown in integrity of the oral epithelium. This study refined a methodology used to detect endotoxin activity in the serum of subjects with indolent periodontal infections. Material and Methods: The QCL® Kinetic Chromogenic Assay (Cambrex) is a kinetic measure of endotoxin activity. Sera from 211 pregnant women with periodontitis enrolled in the Obstetrics and Periodontal Therapy Trial were used to develop the assay further and to evaluate the detection of endotoxin activity that might accompany a low-level bacteremia in chronic periodontitis. Results: We optimized the system to increase the sensitivity and reproducibility of the assay. The refined system was able to detect endotoxin activity in serum at > 0.0125 EU/mL. At baseline (13–16 wk of gestation), 35.5% of the women were positive for endotoxin activity (1.62 ± 2.21; range: 0.38–15 EU/mL). Conclusion: This report describes a sensitive measure of endotoxin activity in serum. The procedure allowed us to document levels of this microbial virulence factor in serum of individuals with indolent infections such as periodontal disease. PMID:20465752

  2. Synthesis and Biological Evaluation of Aminonaphthols Incorporated Indole Derivatives

    PubMed Central

    Anand Raghunath, Saundane; Nandibeoor Mathada, Kirankumar

    2014-01-01

    An efficient one pot condensation of naphthols (1), 2,5-disubstituted indole-3-carboxaldehydes (2), and secondary amines (3) has been achieved using dichloromethane as a solvent, stirring at room temperature. Some of the new [(disubstituted amino)(5-substituted 2-phenyl-1H-indol-3-yl)methyl]naphthalene-ols (4) derivatives were prepared in good yields. The significant features of this method are simple work-up procedure, inexpensive nontoxic solvent, shorter reaction times, and excellent product yields. The structures of newly synthesized compounds (4a–r) are confirmed by their elemental analysis, FTIR, 1H and 13C NMR, and mass spectral data. These compounds were screened for their in vitro antioxidant, antimicrobial, antitubercular, and anticancer activities. Among the synthesized compounds (4a–r), the compound 4e exhibited highest activity for radical scavenging and ferric ions reducing antioxidant power activities; compounds 4b, 4h, and 4k showed good metal chelating activity. Compounds 4n and 4q showed excellent antimicrobial activities with MIC value 08 µg/mL against tested strains. Compounds 4h, 4k, 4n, and 4q exhibited promising antitubercular activity with MIC value 12.5 µg/mL. Compounds 4k and 4q exhibited 100% cell lysis at concentration 10 µg/mL against MDA-MB-231 (human adenocarcinoma mammary gland) cell lines. PMID:25383220

  3. Indole based Tubulin Polymerization Inhibitors: An Update on Recent Developments.

    PubMed

    Sunil, Dhanya; Kamath, Pooja R

    2016-01-01

    The exploration of cancer microenvironment and its physiology have exposed a number of potential molecular targets for selective therapeutic intervention by anti-cancer agents. Microtubules are basic cell components formed by polymerization of αβ heterodimers which play a pivotal role in cellular functions as well as cell division. Drugs that can control the microtubule assembly either by hindering tubulin polymerization or by obstructing microtubule disassembly are of great importance in anti-cancer therapy. Diverse classes of naturally occurring as well as synthetic and semi-synthetic compounds with an indole nucleus induce microtubule polymerization and depolymerization and thereby change tubulin dynamics. Rapid development of several novel tubulin polymerization inhibitors has been observed over the past few years and some of them have associated vascular disrupting properties too. The present review starts with the structure, function and importance of microtubules in a eukaryotic cell. The well characterized tubulin binding domains and the corresponding inhibitors including their mechanism of action is also a part of this article. The report mainly focuses on the brief synthetic methodology with the relevant SAR studies of different indole derived molecules that have been reported in the past few years as potential inhibitors of tubulin polymerization is discussed. This review will provide the up-to-date evidence-base for synthetic chemists as well as biologists to design and synthesize new active molecules to inhibit tubulin polymerization.

  4. A new indole glycoside from the seeds of Raphanus sativus.

    PubMed

    Jin, Hong-Guang; Ko, Hae Ju; Chowdhury, Md Anisuzzaman; Lee, Dong-Sung; Woo, Eun-Rhan

    2016-06-01

    A new indole glycoside, β-D-glucopyranosyl 2-(methylthio)-1H-indole-3-carboxylate, named raphanuside A (1), as well as eight known compounds, β-D-fructofuranosyl-(2 → 1)-(6-O-sinapoyl)-α-D-glucopyranoside (2), (3-O-sinapoyl)-β-D-fructofuranosyl-(2 → 1)-α-D-glucopyranoside (3), (3-O-sinapoyl)-β-D-fructofuranosyl-(2 → 1)-(6-O-sinapoyl)-α-D-glucopyranoside (4), (3,4-O-disinapoyl)-β-D-fructofuranosyl-(2 → 1)-(6-O-sinapoyl)-α-D-glucopyranoside (5), isorhamnetin 3,4'-di-O-β-D-glucoside (6), isorhamnetin 3-O-β-D-glucoside-7-O-α-L-rhamnoside (7), isorhamnetin 3-O-β-D-glucoside (8) and 3'-O-methyl-(-)-epicatechin 7-O-β-D-glucoside (9) were isolated from the seeds of Raphanus sativus. Furthermore, compounds 1-3 and 6-9, were isolated from this plant for the first time. The structures of compounds 1-9 were identified using 1D and 2D NMR, including (1)H-(1)H COSY, HSQC, HMBC and NOESY spectroscopic analyses. The inhibitory activity of these isolated compounds against interleukin-6 (IL-6) production in TNF-α stimulated MG-63 cells was also examined.

  5. A multi-component domino reaction for the direct access to polyfunctionalized indoles via intermolecular allylic esterification and indolation†

    PubMed Central

    Jiang, Bo; Yi, Mian-Shuai; Shi, Feng; Pindi, Suresh; McDowell, Patrick

    2013-01-01

    A novel multi-component reaction for the synthesis of polyfunctionalized indoles and bis-indoles has been established. The reaction pathways were controlled by varying enamines with different substitution patterns to give polyfunctionalized indoles and bis-indoles selectively. The reaction proceeds at a fast speed within 15–30 min with water as the major byproduct, which makes work-up convenient. PMID:22038299

  6. FeCl3-mediated Friedel-Crafts hydroarylation with electrophilic N-acetyl indoles for the synthesis of benzofuroindolines.

    PubMed

    Beaud, Rodolphe; Guillot, Régis; Kouklovsky, Cyrille; Vincent, Guillaume

    2012-12-07

    IRONic electrophilic indoles! The C3-regioselective hydroarylation of N-acetyl indoles with aromatic nucleophiles mediated by FeCl(3) features a rare example of the electrophilic reactivity of the indole core in a Friedel-Crafts reaction. This indole umpolung allows us straightforward access to the tetracyclic benzofuroindoline motif found in the natural product diazonamide A, which is a potent antitumor agent. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Arabidopsis cytochrome P450s that catalyze the first step of tryptophan-dependent indole-3-acetic acid biosynthesis

    PubMed Central

    Hull, Anna K.; Vij, Rekha; Celenza, John L.

    2000-01-01

    Plants synthesize numerous secondary metabolites that are used as developmental signals or as defense against pathogens. Tryptophan (Trp)-derived secondary metabolites include camalexin, indole glucosinolates, and indole-3-acetic acid (IAA); however, the steps in their synthesis from Trp or its precursors remain unclear. We have identified two Arabidopsis cytochrome P450s (CYP79B2 and CYP79B3) that can convert Trp to indole-3-acetaldoxime (IAOx), a precursor to IAA and indole glucosinolates. PMID:10681464

  8. IR spectroscopy of pyridine-water structures in helium nanodroplets.

    PubMed

    Nieto, Pablo; Letzner, Melanie; Endres, Torsten; Schwaab, Gerhard; Havenith, Martina

    2014-05-14

    We present the results of an IR spectroscopic study of pyridine-water heterodimer formation in helium nanodroplets. The experiments were carried out in the frequency range of the pyridine C-H stretch region (3055-3100 cm(-1)) and upon water deuteration in the D-O stretch region (2740-2800 cm(-1)). In order to come to an unambiguous assignment we have determined the angle between the permanent dipole and the vibrational transition moment of the aggregates. The experiments have been accompanied by theoretical simulations which yielded two minimum structures with a 16.28 kJ mol(-1) energy difference. The experimentally observed bands were assigned to two structures with different H-bonds: an N···H bond and a bifurcated O···H-C bond.

  9. Crystal structure of bis(pyridine betaine) hydrochloride monohydrate

    NASA Astrophysics Data System (ADS)

    Xiao-Ming, Chen; Mak, Thomas C. W.

    1990-04-01

    Bis(pyridine betaine) hydrochloride monohydrate, 2C 5H 5NCH 2COO·HCl·H 2O, crystallizes in space group Pnna (No. 52), with a=15.623(3), b=19.707(3), c=5.069(1) Å, and Z=4. The structure has been refined to RF=0.067 for 1207 observed (| F0|>6σ| F0|) Mo Kα data. The carboxylate groups of a pair of pyridine betaine molecules are bridged by a proton to form a centrosymmetric dimer featuring a very strong hydrogen bond of length 2.436(6) Å. The crystal structure comprises a packing of such [(C 5H 5NCH 2COO) 2H] + moieties and hydrogen-bonded (Cl -{dH 2O} ∞) zigzag chains running parallel to the c axis.

  10. Application of Fischer Indolization under Green Conditions using Deep Eutectic Solvents.

    PubMed

    Kotha, Sambasivarao; Chakkapalli, Chandravathi

    2017-04-05

    Indole and its derivatives captured the attention of organic chemists due to their applications in medicinal chemistry. The examples covered here are intricate polycyclic indole derivatives and these include: azapolyquinanes, cyclophanes, spirocycles and other heterocycles. We found that deep eutectic mixture such as L-(+)-tartaric acid (TA) and dimethyl urea (DMU) is useful to prepare complex unnatural indole derivatives. These conditions from time to time produced indole derivatives which are not possible by conventional methods. Various substrates containing multiple carbonyl groups were shown to undergo Fischer indolization (FI) in deep eutectic mixtures and thus expand its scope to a higher level. © 2017 The Chemical Society of Japan & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. Four new minor brominated indole related alkaloids with antibacterial activities from Laurencia similis.

    PubMed

    Li, Mei-Chen; Sun, Wen-Shuang; Cheng, Wei; Liu, Dong; Liang, Hong; Zhang, Qing-Ying; Lin, Wen-Han

    2016-08-01

    Four new minor brominated indole related alkaloids (one indoles, 1, one 1,3-dihydro-indole-2-one, 2, one carbazole, 3, and one 2-carbonylamino-benzoate, 4) were isolated and identified from Laurencia similis by extensive chromatographic and spectrometric methods. Among them, 1 and 2 were the first example of naturally occurring indole with 3-benzyl group and 1,3-dihydro-indole-2-one with 2-isopropylidene group, respectively, whereas 3 and 4 were the first carbazole alkaloids and 2-carbonylamino-benzoate, respectively, isolated from the genus Laurencia. Moreover, 1 showed the most potent antibacterial activity against seven bacterial strains with MIC values ranging from 2 to 8μg/mL. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. Asymmetric synthesis of N-allylic indoles via regio- and enantioselective allylation of aryl hydrazines

    PubMed Central

    Xu, Kun; Gilles, Thomas; Breit, Bernhard

    2015-01-01

    The asymmetric synthesis of N-allylic indoles is important for natural product synthesis and pharmaceutical research. The regio- and enantioselective N-allylation of indoles is a true challenge due to the favourable C3-allylation. We develop here a new strategy to the asymmetric synthesis of N-allylic indoles via rhodium-catalysed N-selective coupling of aryl hydrazines with allenes followed by Fischer indolization. The exclusive N-selectivities and good to excellent enantioselectivities are achieved applying a rhodium(I)/DTBM-Segphos or rhodium(I)/DTBM-Binap catalyst. This method permits the practical synthesis of valuable chiral N-allylated indoles, and avoids the N- or C-selectivity issue. PMID:26137886

  13. SMT-A07, a 3-(Indol-2-yl) indazole derivative, induces apoptosis of leukemia cells in vitro.

    PubMed

    Qian, Shijing; Cao, Ji; Yan, Yan; Sun, Maotang; Zhu, Hong; Hu, Yongzhou; He, Qiaojun; Yang, Bo

    2010-12-01

    N-(2-(1H-indazol-3-yl)-1H-pyrrolo[3,2-b]pyridin-5-yl)-4-chloro-N-methylbenzamide (SMT-A07) is a novel 3-(Indol-2-yl) indazole derivative. The anticancer activities in vitro and the cell apoptosis-induction abilities of SMT-A07 on human leukemia HL60 and NB4 cell lines were investigated in this study. The results of MTT assay showed SMT-A07 was a potential and highly efficient antitumor compound with IC(50) values ranging from 0.09 to 1.19 μM in five leukemia cell lines. SMT-A07 treatment for 24 h caused the increment of apoptosis rate from 6.88 to 49.72% in HL60 cells and from 8.72 to 56.28% in NB4 cells by flow cytometry analysis. Agarose gel electrophoresis showed DNA fragmentation that appeared after cells were exposed to SMT-A07. After SMT-A07 incubation, DAPI staining revealed the presence of DNA fragmentation, and perinuclear apoptotic body. SMT-A07 also resulted in a loss of ΔΨm in both HL60 and NB4 cells by JC-1 staining. Moreover, apoptosis-related proteins were examined by western blotting to explore the mechanism of its cytotoxicity. SMT-A07 exposure caused down-regulation and cleavage of procaspase-8, procaspase-3, Bid, PARP and up-regulation of cleaved caspase-8, cleaved caspase-3, PARP (Cleaved Fragment). In addition, the presence of pan-caspase inhibitor BOC-D-FMK prevented cells from caspase-3 activation, PARP cleavage, and subsequent apoptosis. Our study demonstrates that SMT-A07 displays an apparent antitumor activity with extensive anti-leukemia spectrum, and SMT-A07 can induce the apoptosis of HL60 and NB4 cells activation of the caspase cascade, which deserves further development.

  14. Pd-Catalyzed Cyclocarbonylation of 2-(2-Bromoaryl)indoles with CO as a C1 Source: Selective Access to 6 H-Isoindolo[2,1-a]indol-6-ones and Indeno[1,2-b]indol-10(5 H)-ones.

    PubMed

    Guo, Shenghai; Tao, Li; Wang, Fang; Fan, Xuesen

    2016-11-07

    A highly efficient and regioselective synthetic route to 6 H-isoindolo[2,1-a]indol-6-ones and indeno[1,2-b]indol-10(5 H)-ones through the Pd-catalyzed cyclocarbonylation of 2-(2-bromoaryl)indoles under atmospheric CO pressure has been achieved. Notably, the regioselectivity of the reaction was exclusively dependent on the structural characteristics of the indole substrates. With N-unsubstituted indoles as the starting materials, the reaction afforded 6H-isoindolo[2,1-a]indol-6-ones in good-to-excellent yields. On the other hand, with N-substituted indoles as the substrates, the reaction gave indeno[1,2-b]indol-10(5 H)-ones in a highly regioselective manner.

  15. Simultaneous extraction and HPLC determination of 3-indole butyric acid and 3-indole acetic acid in pea plant by using ionic liquid-modified silica as sorbent.

    PubMed

    Sheikhian, Leila; Bina, Sedigheh

    2016-01-15

    In this study, ionic liquid-modified silica was used as sorbent for simultaneous extraction and preconcentration of 3-indole butyric acid and 3-indole acetic acid in pea plants. The effect of some parameters such as pH and ionic strength of sample solution, amount of sorbent, flow rate of aqueous sample solution and eluent solution, concentration of eluent solution, and temperature were studied for each hormone solution. Percent extraction of 3-indole butyric acid and 3-indole acetic acid was strongly affected by pH of aqueous sample solution. Ionic strength of aqueous phase and temperature showed no serious effects on extraction efficiency of studied plant hormones. Obtained breakthrough volume was 200mL for each of studied hormones. Preconcentration factor for spectroscopic and chromatographic determination of studied hormones was 100 and 4.0×10(3) respectively. Each solid sorbent phase was reusable for almost 10 times of extraction/stripping procedure. Relative standard deviations of extraction/stripping processes of 3-indole butyric acid and 3-indole acetic acid were 2.79% and 3.66% respectively. The calculated limit of detections for IBA and IAA were 9.1×10(-2)mgL(-1) and 1.6×10(-1)mgL(-1) respectively.

  16. Effect of boiling on the content of ascorbigen, indole-3-carbinol, indole-3-acetonitrile, and 3,3'-diindolylmethane in fermented cabbage.

    PubMed

    Ciska, Ewa; Verkerk, Ruud; Honke, Joanna

    2009-03-25

    The aim of the study was to investigate the effect of the boiling process on the content of ascorbigen, indole-3-carbinol, indole-3-acetonitrile, and 3,3'-diindolylmethane in fermented cabbage. The cabbage was boiled for 5 to 60 min. Boiling resulted in a decrease of the total content of the compounds analysed. The changes were mainly caused by leaching of ascorbigen predominating in cabbage into cooking water and by its thermal hydrolysis. Ascorbigen losses resulting from thermal hydrolysis accounted for 30% after 10 min of boiling and for 90% after 60 min of boiling. One of the ascorbigen breakdown products was indole 3 carbinol; the decrease in ascorbigen content was accompanied by a drastic increase in the content of 3,3'-diindolylmethane, a condensation product of indole-3-carbinol. After 40 and 50 min of boiling, the total content of 3,3'-diindolylmethane in cabbage and cooking water was approximately 0.2 micromol/100 g and was 6-fold higher than that in uncooked cabbage. 3,3'-Diindolylmethane synthesis proceeded within the plant tissue. After 10 min of boiling, the content of free indole-3-carbinol and indole-3-acetonitrile stabilized at the level of about 80% as compared to the uncooked cabbage.

  17. Ab initio multiple cloning simulations of pyrrole photodissociation: TKER spectra and velocity map imaging

    SciTech Connect

    Makhov, Dmitry V.; Saita, Kenichiro; Martinez, Todd J.; Shalashilin, Dmitrii V.

    2014-12-11

    In this study, we report a detailed computational simulation of the photodissociation of pyrrole using the ab initio Multiple Cloning (AIMC) method implemented within MOLPRO. The efficiency of the AIMC implementation, employing train basis sets, linear approximation for matrix elements, and Ehrenfest configuration cloning, allows us to accumulate significant statistics. We calculate and analyze the total kinetic energy release (TKER) spectrum and Velocity Map Imaging (VMI) of pyrrole and compare the results directly with experimental measurements. Both the TKER spectrum and the structure of the velocity map image (VMI) are well reproduced. Previously, it has been assumed that the isotropic component of the VMI arises from long time statistical dissociation. Instead, our simulations suggest that ultrafast dynamics contributes significantly to both low and high energy portions of the TKER spectrum.

  18. Both visual and fluorescent sensors for Zn2 + based on bis(pyrrol-2-yl-methyleneamine) platform

    NASA Astrophysics Data System (ADS)

    Wu, Wei-Na; Mao, Pan-Dong; Jia, Lei; Wang, Yuan; Xu, Zhou-Qing

    2016-09-01

    Two bis(pyrrol-2-yl-methyleneamine) chemo-sensors, 1, 3- and 1, 4-bis[3,4-dimethyl-5-ethyloxy -carbonyl-pyrrol-2-yl-methyleneamine]benzene (H2L1 and H2L2, respectively) have been synthesized and characterized, which exhibit high selectivity as off-on fluorescence sensors toward Zn2 + in CH3CN/H2O (9:1, v/v) solution. The detection limits of both sensors are at the parts per million level. Moreover, the probes H2L1 and H2L2 could sense Zn2 + by "naked eye" with a color change from colorless to yellow, and from yellow to dark yellow, respectively. To test the practical use of the probes, the determination of Zn2 + in real water samples was also evaluated.

  19. Comparative Analysis of the Antineoplastic Activity of C60 Fullerene with 5-Fluorouracil and Pyrrole Derivative In Vivo

    NASA Astrophysics Data System (ADS)

    Lynchak, O. V.; Prylutskyy, Yu I.; Rybalchenko, V. K.; Kyzyma, O. A.; Soloviov, D.; Kostjukov, V. V.; Evstigneev, M. P.; Ritter, U.; Scharff, P.

    2017-01-01

    The antitumor activity of pristine C60 fullerene aqueous solution (C60FAS) compared to 5-fluorouracil (5-FU) and pyrrole derivative 1-(4-Cl-benzyl)-3-Cl-4-(CF3-fenylamino)-1H-pyrrol-2.5-dione (MI-1) cytostatic drugs was investigated and analyzed in detail using the model of colorectal cancer induced by 1.2-dimethylhydrazine (DMH) in rats. The number, size, and location of the tumors were measured, and the pathology was examined. It was found that the number of tumors and total lesion area decreased significantly under the action of C60FAS and MI-1. Because these drugs have different mechanisms of action, their simultaneous administration can potentially increase the effectiveness and significantly reduce the side effects of antitumor therapy.

  20. Bandgap Engineering in π-Extended Pyrroles. A Modular Approach to Electron-Deficient Chromophores with Multi-Redox Activity.

    PubMed

    Zhylitskaya, Halina; Cybińska, Joanna; Chmielewski, Piotr; Lis, Tadeusz; Stępień, Marcin

    2016-09-07

    A family of bandgap-tunable pyrroles structurally related to rylene dyes was computationally designed and prepared using robust, easily scalable chemistry. These pyrroles show highly variable fluorescence properties and can be used as building blocks for the synthesis of electron-deficient oligopyrroles. The latter application is demonstrated through the development of π-extended porphyrins containing naphthalenediamide or naphthalenediimide units. These new macrocycles exhibit simultaneously tunable visible and near-IR absorptions, an ability to accept up to 8 electrons via electrochemical reduction, and high internal molecular free volumes. When chemically reduced under inert conditions, the most electron-deficient of these macrocycles revealed reversible formation of eight charged states, characterized by remarkably red-shifted optical absorptions, extending beyond 2200 nm. Such features make these oligopyrroles of interest as functional chromophores, charge-storage materials, and tectons for crystal engineering.

  1. Pyrrole Oligoglycosides from the Starfish Acanthaster planci Suppress Lipopolysaccharide-Induced Nitric Oxide Production in RAW264.7 Macrophages.

    PubMed

    Vien, Le Thi; Hanh, Tran Thi Hong; Huong, Phan Thi Thanh; Dang, Nguyen Hai; Thanh, Nguyen Van; Lyakhova, Ekaterina; Cuong, Nguyen Xuan; Nam, Nguyen Hoai; Kiem, Phan Van; Kicha, Alla; Minh, Chau Van

    2016-11-01

    Two new pyrrole oligoglycosides, plancipyrrosides A and B (1 and 2), were isolated from methanol extract of the Vietnamese starfish Acanthaster planci using various chromatographic procedures. Their structures were elucidated by spectroscopic methods including one and two dimensional (1D- and 2D)-NMR and Fourier transform ion cyclotron resonance (FT-ICR)-MS. The finding of 1 and 2 represents the third case of pyrrole oligoglycosides obtaining reported to date. Moreover, plancipyrroside B (2) exhibits a potent inhibitory effect on lipopolysaccharide (LPS)-induced nitric oxide (NO) production in RAW264.7 cells with IC50 of 5.94±0.34 µM, whereas plancipyrroside A (1) shows this inhibitory activity with IC50 of 16.61±1.85 µM.

  2. Lipophilic 2,5-Disubstituted Pyrroles from the Marine Sponge Mycale sp. Inhibit Mitochondrial Respiration and HIF-1 Activation

    PubMed Central

    Mao, Shui-Chun; Liu, Yang; Morgan, J. Brian; Jekabsons, Mika B.; Zhou, Yu-Dong; Nagle, Dale G.

    2010-01-01

    The lipid extract of the marine sponge Mycale sp. inhibited the activation of hypoxiainducible factor-1 (HIF-1) in a human breast tumor T47D cell-based reporter assay. Bioassay-guided isolation and structure elucidation yielded 18 new lipophilic 2,5-disubstituted pyrroles, and eight structurally related known compounds. The active compounds inhibited hypoxia-induced HIF activation with moderate potency (IC50 values < 10 μM). Mechanistic studies revealed that the active compounds suppressed mitochondrial respiration by blocking NADH-ubiquinone oxidoreductase (complex I) at concentrations that inhibited HIF-1 activation. Under hypoxic conditions, reactive oxygen species produced by mitochondrial complex III are believed to act as a signal of cellular hypoxia that leads to HIF-1α protein induction and activation. By inhibiting electron transport (or delivery) to complex III under hypoxic conditions, lipophilic Mycale pyrroles appear to disrupt mitochondrial ROS-regulated HIF-1 signaling. PMID:19845338

  3. trans-Dibromidotetra-kis-(pyridine-κN)ruthenium(II).

    PubMed

    Wu, Xiu-Li; Ye, Ru-Fei; Jia, Ai-Quan; Chen, Qun; Zhang, Qian-Feng

    2013-02-01

    The title complex, [RuBr(2)(C(5)H(5)N)(4)], contains two independent complex mol-ecules in each of which the Ru(II) atom is located on a site of 222 symmetry and has a distorted octa-hedral coordination geometry with four pyridine N atoms and two Br atoms. The Br aroms are trans-disposed as a result of symmetry.

  4. Indole production promotes Escherichia coli mixed-culture growth with Pseudomonas aeruginosa by inhibiting quorum signaling.

    PubMed

    Chu, Weihua; Zere, Tesfalem R; Weber, Mary M; Wood, Thomas K; Whiteley, Marvin; Hidalgo-Romano, Benjamin; Valenzuela, Ernesto; McLean, Robert J C

    2012-01-01

    Indole production by Escherichia coli, discovered in the early 20th century, has been used as a diagnostic marker for distinguishing E. coli from other enteric bacteria. By using transcriptional profiling and competition studies with defined mutants, we show that cyclic AMP (cAMP)-regulated indole formation is a major factor that enables E. coli growth in mixed biofilm and planktonic populations with Pseudomonas aeruginosa. Mutants deficient in cAMP production (cyaA) or the cAMP receptor gene (crp), as well as indole production (tnaA), were not competitive in coculture with P. aeruginosa but could be restored to wild-type competitiveness by supplementation with a physiologically relevant indole concentration. E. coli sdiA mutants, which lacked the receptor for both indole and N-acyl-homoserine lactones (AHLs), showed no change in competitive fitness, suggesting that indole acted directly on P. aeruginosa. An E. coli tnaA mutant strain regained wild-type competiveness if grown with P. aeruginosa AHL synthase (rhlI and rhlI lasI) mutants. In contrast to the wild type, P. aeruginosa AHL synthase mutants were unable to degrade indole. Indole produced during mixed-culture growth inhibited pyocyanin production and other AHL-regulated virulence factors in P. aeruginosa. Mixed-culture growth with P. aeruginosa stimulated indole formation in E. coli cpdA, which is unable to regulate cAMP levels, suggesting the potential for mixed-culture gene activation via cAMP. These findings illustrate how indole, an early described feature of E. coli central metabolism, can play a significant role in mixed-culture survival by inhibiting quorum-regulated competition factors in P. aeruginosa.

  5. Geometrical features of hydrogen bonded complexes involving sterically hindered pyridines.

    PubMed

    Andreeva, Daria V; Ip, Brenda; Gurinov, Andrey A; Tolstoy, Peter M; Denisov, Gleb S; Shenderovich, Ilja G; Limbach, Hans-Heinrich

    2006-09-21

    The ability of strongly sterically hindered pyridines to form hydrogen bonded complexes was inspected using low-temperature 1H and 15N NMR spectroscopy in a liquefied Freon mixture. The proton acceptors were 2,6-di(tert-butyl)-4-methyl- and 2,6-di(tert-butyl)-4-diethylaminopyridine; the proton donors were hydrogen tetrafluoroborate, hydrogen chloride, and hydrogen fluoride. The presence of the tert-butyl groups in the ortho positions dramatically perturbed the geometry of the forming hydrogen bonds. As revealed by experiment, the studied crowded pyridines could form hydrogen bonded complexes with proton donors exclusively through their protonation. Even the strongest small proton acceptor, anion F-, could not be received by the protonated base. Instead, the simplest hydrogen bonded complex involved the [FHF]- anion. This complex was characterized by the shortest possible N...F distance of about 2.8 A. Because the ortho tert-butyl groups did not prevent the hydrogen bond interaction between the protonated center and the anion completely, an increase of the pyridine basicity caused a further shortening of the N-H distance and a weakening of the hydrogen bond to the counterion.

  6. DNA ligase and the pyridine nucleotide cycle in Salmonella typhimurium.

    PubMed Central

    Park, U E; Olivera, B M; Hughes, K T; Roth, J R; Hillyard, D R

    1989-01-01

    Bacterial DNA ligases use NAD as an energy source. In this study we addressed two questions about these enzymes. First, what is the physiological consequence of completely removing the NAD-dependent enzyme and replacing it with an ATP-dependent DNA ligase? We constructed Salmonella typhimurium strains in which the endogenous NAD-dependent DNA ligase activity was inactivated by an insertion mutation and the ATP-dependent enzyme from bacteriophage T4 was provided by a cloned phage gene. Such strains were physiologically indistinguishable from the wild type, even under conditions of UV irradiation or treatment with alkylating agents. These results suggest that specific functional interactions between DNA ligase and other replication and repair enzymes may be unimportant under the conditions tested. Second, the importance of DNA ligation as the initiating event of the bacterial pyridine nucleotide cycle was critically assessed in these mutant strains. Surprisingly, our results indicate that DNA ligation makes a minimal contribution to the pyridine nucleotide cycle; the Salmonella strains with only an ATP-dependent ligase had the same NAD turnover rates as the wild-type strain with an NAD-dependent ligase. However, we found that NAD turnover was significantly decreased under anaerobic conditions. We suggest that most intracellular pyridine nucleotide breakdown occurs in a process that protects the cell against oxygen damage but involves a biochemical mechanism other than DNA ligation. Images PMID:2649488

  7. Pyridine metabolism in tea plants: salvage, conjugate formation and catabolism.

    PubMed

    Ashihara, Hiroshi; Deng, Wei-Wei

    2012-11-01

    Pyridine compounds, including nicotinic acid and nicotinamide, are key metabolites of both the salvage pathway for NAD and the biosynthesis of related secondary compounds. We examined the in situ metabolic fate of [carbonyl-(14)C]nicotinamide, [2-(14)C]nicotinic acid and [carboxyl-(14)C]nicotinic acid riboside in tissue segments of tea (Camellia sinensis) plants, and determined the activity of enzymes involved in pyridine metabolism in protein extracts from young tea leaves. Exogenously supplied (14)C-labelled nicotinamide was readily converted to nicotinic acid, and some nicotinic acid was salvaged to nicotinic acid mononucleotide and then utilized for the synthesis of NAD and NADP. The nicotinic acid riboside salvage pathway discovered recently in mungbean cotyledons is also operative in tea leaves. Nicotinic acid was converted to nicotinic acid N-glucoside, but not to trigonelline (N-methylnicotinic acid), in any part of tea seedlings. Active catabolism of nicotinic acid was observed in tea leaves. The fate of [2-(14)C]nicotinic acid indicates that glutaric acid is a major catabolite of nicotinic acid; it was further metabolised, and carbon atoms were finally released as CO(2). The catabolic pathway observed in tea leaves appears to start with the nicotinic acid N-glucoside formation; this pathway differs from catabolic pathways observed in microorganisms. Profiles of pyridine metabolism in tea plants are discussed.

  8. A Novel Porphyrin-Containing Polyimide Nanofibrous Membrane for Colorimetric and Fluorometric Detection of Pyridine Vapor

    PubMed Central

    Lv, Yuanyuan; Zhang, Yani; Du, Yanglong; Xu, Jiayao; Wang, Junbo

    2013-01-01

    A novel zinc porphyrin-containing polyimide (ZPCPI) nanofibrous membrane for rapid and reversible detection of trace amounts of pyridine vapor is described. The membrane displays a distinct color change, as well as dramatic variations in absorption and fluorescent emission spectra, upon exposure to pyridine vapor. This condition allows the detection of the analyte at concentrations as low as 0.041 ppm. The vapochromic and spectrophotometric responses of the membrane are attributed to the formation of the ZPCPI-pyridine complex upon axial coordination. From surface plasmon resonance analysis, the affinity constant of ZPCPI-pyridine complex was calculated to be (3.98 ± 0.25) × 104 L·mol−1. The ZPCPI nanofibrous membrane also showed excellent selectivity for pyridine vapor over other common amines, confirming its applicability in the manufacture of pyridine-sensitive gas sensors. PMID:24256976

  9. Formation of pyrazines and a novel pyrrole in Maillard model systems of 1,3-dihydroxyacetone and 2-oxopropanal.

    PubMed

    Adams, An; Polizzi, Viviana; van Boekel, Martinus; De Kimpe, Norbert

    2008-03-26

    Alkylpyrazines are a very important class of Maillard flavor compounds, but their mechanism of formation is complex and consists of different pathways. The model reaction of 20 different amino acids with 1,3-dihydroxyacetone, as a precursor of 2-oxopropanal, was studied by means of SPME-GC-MS to investigate the involvement of the amino acid side chain in the substitution pattern of the resulting pyrazines. 2,5-Dimethylpyrazine was quantitatively the most important pyrazine formed from all of the amino acids. The amino acid side chain is not involved in its formation. The substituents of other less abundant pyrazines resulted mainly from the incorporation of the Strecker aldehyde or aldol condensation products in the intermediate dihydropyrazine. The importance of different reaction mechanisms was evaluated, taking into account the pattern of pyrazines identified. In the solvent extracts of aqueous model reactions of 2-oxopropanal with amino acids, the main reaction product was not a pyrazine but a novel pyrrole. This pyrrole was identified as 2,5-diacetyl-3-methyl-1 H-pyrrole by means of spectral analysis, secured by chemical synthesis. A reaction mechanism for its formation was proposed and evaluated. The influence of various reaction conditions on the formation of 2,5-diacetyl-3-methyl-1 H-pyrrole and 2,5-dimethylpyrazine in the model reaction of alanine with 2-oxopropanal was studied. These results underscore the importance of the ratio of the different reagents and the presence of water in the resulting flavor formation in the Maillard reaction.

  10. Cation-π interaction of the univalent silver cation with meso-octamethylcalix[4]pyrrole: Experimental and theoretical study

    NASA Astrophysics Data System (ADS)

    Polášek, Miroslav; Kvíčala, Jaroslav; Makrlík, Emanuel; Křížová, Věra; Vaňura, Petr

    2017-02-01

    By using electrospray ionization mass spectrometry (ESI-MS), it was proven experimentally that the univalent silver cation Ag+ forms with meso-octamethylcalix[4]pyrrole (abbrev. 1) the cationic complex species 1·Ag+. Further, applying quantum chemical DFT calculations, four different conformations of the resulting complex 1·Ag+ were derived. It means that under the present experimental conditions, this ligand 1 can be considered as a macrocyclic receptor for the silver cation.

  11. Visible-light-induced formal [3+2] cycloaddition for pyrrole synthesis under metal-free conditions.

    PubMed

    Xuan, Jun; Xia, Xu-Dong; Zeng, Ting-Ting; Feng, Zhu-Jia; Chen, Jia-Rong; Lu, Liang-Qiu; Xiao, Wen-Jing

    2014-05-26

    A photocatalytic formal [3+2] cycloaddition of 2H-azirines with alkynes has been achieved under irradiation by visible light in the presence of organic dye photocatalysts. This transformation provides efficient access to highly functionalized pyrroles in good yields and has been applied to the synthesis of drug analogues. A primary trial of photocascade catalysis merging energy transfer and redox neutral reactions was shown to be successful. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. Identification of Binding Targets of a Pyrrole-Imidazole Polyamide KR12 in the LS180 Colorectal Cancer Genome

    PubMed Central

    Watanabe, Takayoshi; Kuo, Tony; Shinozaki, Yoshinao; Takatori, Atsushi; Koshikawa, Nobuko; Chandran, Anandhakumar; Otsuki, Joe; Sugiyama, Hiroshi; Horton, Paul

    2016-01-01

    Pyrrole-imidazole polyamides are versatile DNA minor groove binders and attractive therapeutic options against oncological targets, especially upon functionalization with an alkylating agent such as seco-CBI. These molecules also provide an alternative for oncogenes deemed “undruggable” at the protein level, where the absence of solvent-accessible pockets or structural crevices prevent the formation of protein-inhibitor ligands; nevertheless, the genome-wide effect of pyrrole-imidazole polyamide binding remain largely unclear to-date. Here we propose a next-generation sequencing-based workflow combined with whole genome expression arrays to address such issue using a candidate anti-cancer alkylating agent, KR12, against codon 12 mutant KRAS. Biotinylating KR12 enables the means to identify its genome-wide effects in living cells and possible biological implications via a coupled workflow of enrichment-based sequencing and expression microarrays. The subsequent computational pathway and expression analyses allow the identification of its genomic binding sites, as well as a route to explore a polyamide’s possible genome-wide effects. Among the 3,343 KR12 binding sites identified in the human LS180 colorectal cancer genome, the reduction of KR12-bound gene expressions was also observed. Additionally, the coupled microarray-sequencing analysis also revealed some insights about the effect of local chromatin structure on pyrrole-imidazole polyamide, which had not been fully understood to-date. A comparative analysis with KR12 in a different human colorectal cancer genome SW480 also showed agreeable agreements of KR12 binding affecting gene expressions. Combination of these analyses thus suggested the possibility of applying this approach to other pyrrole-imidazole polyamides to reveal further biological details about the effect of polyamide binding in a genome. PMID:27798693

  13. Pyrrole-2-Carboxylic Acid as a Ligand for the Cu-Catalyzed Reactions of Primary Anilines with Aryl Halides

    PubMed Central

    Altman, Ryan A.; Anderson, Kevin W.; Buchwald, Stephen L.

    2008-01-01

    Pyrrole 2-carboxylic acid (L5) was found to be an effective ligand for the Cu-catalyzed mono-arylation of anilines with aryl iodides and bromides. Under the reported conditions (10% CuI/20% L5/DMSO/K3PO4/80–100 °C/20–24 h), a variety of useful functional groups were tolerated, and moderate to good yields of the diaryl amine products were obtained. PMID:18543973

  14. Identification of Binding Targets of a Pyrrole-Imidazole Polyamide KR12 in the LS180 Colorectal Cancer Genome.

    PubMed

    Lin, Jason; Hiraoka, Kiriko; Watanabe, Takayoshi; Kuo, Tony; Shinozaki, Yoshinao; Takatori, Atsushi; Koshikawa, Nobuko; Chandran, Anandhakumar; Otsuki, Joe; Sugiyama, Hiroshi; Horton, Paul; Nagase, Hiroki

    2016-01-01

    Pyrrole-imidazole polyamides are versatile DNA minor groove binders and attractive therapeutic options against oncological targets, especially upon functionalization with an alkylating agent such as seco-CBI. These molecules also provide an alternative for oncogenes deemed "undruggable" at the protein level, where the absence of solvent-accessible pockets or structural crevices prevent the formation of protein-inhibitor ligands; nevertheless, the genome-wide effect of pyrrole-imidazole polyamide binding remain largely unclear to-date. Here we propose a next-generation sequencing-based workflow combined with whole genome expression arrays to address such issue using a candidate anti-cancer alkylating agent, KR12, against codon 12 mutant KRAS. Biotinylating KR12 enables the means to identify its genome-wide effects in living cells and possible biological implications via a coupled workflow of enrichment-based sequencing and expression microarrays. The subsequent computational pathway and expression analyses allow the identification of its genomic binding sites, as well as a route to explore a polyamide's possible genome-wide effects. Among the 3,343 KR12 binding sites identified in the human LS180 colorectal cancer genome, the reduction of KR12-bound gene expressions was also observed. Additionally, the coupled microarray-sequencing analysis also revealed some insights about the effect of local chromatin structure on pyrrole-imidazole polyamide, which had not been fully understood to-date. A comparative analysis with KR12 in a different human colorectal cancer genome SW480 also showed agreeable agreements of KR12 binding affecting gene expressions. Combination of these analyses thus suggested the possibility of applying this approach to other pyrrole-imidazole polyamides to reveal further biological details about the effect of polyamide binding in a genome.

  15. Transport of the two natural auxins, indole-3-butyric acid and indole-3-acetic acid, in Arabidopsis

    NASA Technical Reports Server (NTRS)

    Rashotte, Aaron M.; Poupart, Julie; Waddell, Candace S.; Muday, Gloria K.; Brown, C. S. (Principal Investigator)

    2003-01-01

    Polar transport of the natural auxin indole-3-acetic acid (IAA) is important in a number of plant developmental processes. However, few studies have investigated the polar transport of other endogenous auxins, such as indole-3-butyric acid (IBA), in Arabidopsis. This study details the similarities and differences between IBA and IAA transport in several tissues of Arabidopsis. In the inflorescence axis, no significant IBA movement was detected, whereas IAA is transported in a basipetal direction from the meristem tip. In young seedlings, both IBA and IAA were transported only in a basipetal direction in the hypocotyl. In roots, both auxins moved in two distinct polarities and in specific tissues. The kinetics of IBA and IAA transport appear similar, with transport rates of 8 to 10 mm per hour. In addition, IBA transport, like IAA transport, is saturable at high concentrations of auxin, suggesting that IBA transport is protein mediated. Interestingly, IAA efflux inhibitors and mutations in genes encoding putative IAA transport proteins reduce IAA transport but do not alter IBA movement, suggesting that different auxin transport protein complexes are likely to mediate IBA and IAA transport. Finally, the physiological effects of IBA and IAA on hypocotyl elongation under several light conditions were examined and analyzed in the context of the differences in IBA and IAA transport. Together, these results present a detailed picture of IBA transport and provide the basis for a better understanding of the transport of these two endogenous auxins.

  16. Transport of the two natural auxins, indole-3-butyric acid and indole-3-acetic acid, in Arabidopsis

    NASA Technical Reports Server (NTRS)

    Rashotte, Aaron M.; Poupart, Julie; Waddell, Candace S.; Muday, Gloria K.; Brown, C. S. (Principal Investigator)

    2003-01-01

    Polar transport of the natural auxin indole-3-acetic acid (IAA) is important in a number of plant developmental processes. However, few studies have investigated the polar transport of other endogenous auxins, such as indole-3-butyric acid (IBA), in Arabidopsis. This study details the similarities and differences between IBA and IAA transport in several tissues of Arabidopsis. In the inflorescence axis, no significant IBA movement was detected, whereas IAA is transported in a basipetal direction from the meristem tip. In young seedlings, both IBA and IAA were transported only in a basipetal direction in the hypocotyl. In roots, both auxins moved in two distinct polarities and in specific tissues. The kinetics of IBA and IAA transport appear similar, with transport rates of 8 to 10 mm per hour. In addition, IBA transport, like IAA transport, is saturable at high concentrations of auxin, suggesting that IBA transport is protein mediated. Interestingly, IAA efflux inhibitors and mutations in genes encoding putative IAA transport proteins reduce IAA transport but do not alter IBA movement, suggesting that different auxin transport protein complexes are likely to mediate IBA and IAA transport. Finally, the physiological effects of IBA and IAA on hypocotyl elongation under several light conditions were examined and analyzed in the context of the differences in IBA and IAA transport. Together, these results present a detailed picture of IBA transport and provide the basis for a better understanding of the transport of these two endogenous auxins.

  17. Indole-3-butyric acid induces lateral root formation via peroxisome-derived indole-3-acetic acid and nitric oxide.

    PubMed

    Schlicht, Markus; Ludwig-Müller, Jutta; Burbach, Christian; Volkmann, Dieter; Baluska, Frantisek

    2013-10-01

    Controlled plant growth requires regulation through a variety of signaling molecules, including steroids, peptides, radicals of oxygen and nitrogen, as well as the 'classical' phytohormone groups. Auxin is critical for the control of plant growth and also orchestrates many developmental processes, such as the formation of new roots. It modulates root architecture both slowly, through actions at the transcriptional level and, more rapidly, by mechanisms targeting primarily plasma membrane sensory systems and intracellular signaling pathways. The latter reactions use several second messengers, including Ca(2+) , nitric oxide (NO) and reactive oxygen species (ROS). Here, we investigated the different roles of two auxins, the major auxin indole-3-acetic acid (IAA) and another endogenous auxin indole-3-butyric acid (IBA), in the lateral root formation process of Arabidopsis and maize. This was mainly analyzed by different types of fluorescence microscopy and inhibitors of NO production. This study revealed that peroxisomal IBA to IAA conversion is followed by peroxisomal NO, which is important for IBA-induced lateral root formation. We conclude that peroxisomal NO emerges as a new player in auxin-induced root organogenesis. In particular, the spatially and temporally coordinated release of NO and IAA from peroxisomes is behind the strong promotion of lateral root formation via IBA. © 2013 The Authors. New Phytologist © 2013 New Phytologist Trust.

  18. Evaluation of molecular assembly, spectroscopic interpretation, intra-/inter molecular hydrogen bonding and chemical reactivity of two pyrrole precursors

    NASA Astrophysics Data System (ADS)

    Rawat, Poonam; Singh, R. N.

    2014-10-01

    This paper describes the evaluation of conformational, spectroscopic, hydrogen bonding and chemical reactivity of pyrrole precursor: ethyl 3,5 dimethyl-1H-pyrrole-2-carboxylate (EDPC) and ethyl 3,4-dimethyl-4-acetyl-1H-pyrrole-2-carboxylate (EDAPC) for the convenient characterization, synthetic usefulness and comparative evaluations. All experimental spectral values of 1H NMR, UV-Vis and FT-IR spectra coincide well with calculated values by DFT. The orbital interactions in EDPC and EDAPC are found to lengthen their Nsbnd H and Cdbnd O bonds and lowers their vibrational frequencies (red shift) resulting to dimer formation. The QTAIM and NBO analyses provide the strength of interactions and charge transfer in the hydrogen bonding unit and stability of dimers. The binding energy of EDPC and EDPAC dimer are found to be 9.92, 10.22 kcal/mol, respectively. In EDPAC and EDPC dimer, hyperconjugative interactions between monomer units is due to n1(O) → σ*(Nsbnd H) that stabilize the molecule up to 9.7 and 9.3 kcal/mol, respectively. On evaluation of molecular electrostatic potential (MEP) and electronic descriptors for EDPC it has been found that it is a good precursor for synthesis of formyl and acetyl derivatives whereas EDAPC has been found to be a good precursor for synthesis of schiff base, hydrazones, hydrazide-hydrazones and chalcones.

  19. Pyrrole Alkaloids with Potential Cancer Chemopreventive Activity Isolated from a Goji Berry-Contaminated Commercial Sample of African Mango

    PubMed Central

    2015-01-01

    Bioassay-guided fractionation of a commercial sample of African mango (Irvingia gabonensis) that was later shown to be contaminated with goji berry (Lycium sp.) led to the isolation of a new pyrrole alkaloid, methyl 2-[2-formyl-5-(hydroxymethyl)-1H-pyrrol-1-yl]propanoate, 1, along with seven known compounds, 2–8. The structures of the isolated compounds were established by analysis of their spectroscopic data. The new compound 1g showed hydroxyl radical-scavenging activity with an ED50 value of 16.7 μM, whereas 4-[formyl-5-(methoxymethyl)-1H-pyrrol-1-yl]butanoic acid (2) was active in both the hydroxyl radical-scavenging (ED50 11.9 μM) and quinone reductase-induction [CD (concentration required to double QR activity) 2.4 μM)] assays used. The isolated compounds were shown to be absent in a taxonomically authenticated African mango sample but present in three separate authentic samples of goji berry (Lycium barbarum) using LC-MS and 1H NMR fingerprinting analysis, including one sample that previously showed inhibitory activity in vivo in a rat esophageal cancer model induced with N-nitrosomethylbenzylamine. Additionally, microscopic features characteristic of goji berry were observed in the commercial African mango sample. PMID:24792835

  20. Pyrrole alkaloids with potential cancer chemopreventive activity isolated from a goji berry-contaminated commercial sample of African mango.

    PubMed

    Li, Jie; Pan, Li; Naman, C Benjamin; Deng, Ye; Chai, Heebyung; Keller, William J; Kinghorn, A Douglas

    2014-06-04

    Bioassay-guided fractionation of a commercial sample of African mango (Irvingia gabonensis) that was later shown to be contaminated with goji berry (Lycium sp.) led to the isolation of a new pyrrole alkaloid, methyl 2-[2-formyl-5-(hydroxymethyl)-1H-pyrrol-1-yl]propanoate, 1, along with seven known compounds, 2-8. The structures of the isolated compounds were established by analysis of their spectroscopic data. The new compound 1g showed hydroxyl radical-scavenging activity with an ED50 value of 16.7 μM, whereas 4-[formyl-5-(methoxymethyl)-1H-pyrrol-1-yl]butanoic acid (2) was active in both the hydroxyl radical-scavenging (ED50 11.9 μM) and quinone reductase-induction [CD (concentration required to double QR activity) 2.4 μM)] assays used. The isolated compounds were shown to be absent in a taxonomically authenticated African mango sample but present in three separate authentic samples of goji berry (Lycium barbarum) using LC-MS and (1)H NMR fingerprinting analysis, including one sample that previously showed inhibitory activity in vivo in a rat esophageal cancer model induced with N-nitrosomethylbenzylamine. Additionally, microscopic features characteristic of goji berry were observed in the commercial African mango sample.

  1. Synthesis and chemistry of 4,5-dihydrothieno[3,2-b]pyrrol-6-one--a heteroindoxyl.

    PubMed

    Gaywood, Alexander P; McNab, Hamish

    2009-06-05

    Flash vacuum pyrolysis (FVP) of 2-acetyl-3-azidothiophene gives 3-methylthieno[3,2-c]isoxazole as the major product at a furnace temperature of 350 degrees C whereas at temperatures above 550 degrees C the new heteroindoxyl 4,5-dihydrothieno[3,2-b]pyrrol-6-one is exclusively formed. The heteroindoxyl exists predominantly as the keto tautomer. It is O-protonated by TFA, N-acetylated by acetic anhydride, N-nitrosated by nitrous acid, and provides an N-methylene Meldrum's acid derivative on treatment with methoxymethylene Meldrum's acid. Reactions of 4,5-dihydrothieno[3,2-b]pyrrol-6-one with diazonium salts, with isatin, and with dimethyl acetylenedicarboxylate take place at the methylene position to provide a hydrazone, an indirubin analogue, and a succinate derivative, respectively. Oxidation of 4,5-dihydrothieno[3,2-b]pyrrol-6-one gives a heteroindigotin, which shows a hypsochromic shift in the UV spectrum, relative to indigotin itself.

  2. Rare-earth-catalyzed C-H bond addition of pyridines to olefins.

    PubMed

    Guan, Bing-Tao; Hou, Zhaomin

    2011-11-16

    An efficient and general protocol for the ortho-alkylation of pyridines via C-H addition to olefins has been developed, using cationic half-sandwich rare-earth catalysts, which provides an atom-economical method for the synthesis of alkylated pyridine derivatives. A wide range of pyridine and olefin substrates including α-olefins, styrenes, and conjugated dienes are compatible with the catalysts.

  3. Spiroheterocyclization of methyl 1-aryl-3-cinnamoyl-4,5-dioxo-4,5-dihydro-1H-pyrrole-2-carboxylates by the action of 3-(arylamino)-1H-inden-1-ones.

    PubMed

    Silaichev, Pavel S; Filimonov, Valeriy O; Slepukhin, Pavel A; Maslivets, Andrey N

    2012-11-22

    Methyl 1-aryl-3-cinnamoyl-4,5-dioxo-4,5-dihydro-1H-pyrrole-2-carboxylates interact with 3-(arylamino)-1H-inden-1-ones to give the corresponding 1,1'-diaryl-3'-cinnamoyl-4'-hydroxy-1H-spiro[indeno[1,2-b]pyrrole-3,2'-pyrrole]-2,4,5'(1'H)-triones in good yields.

  4. Influence of supramolecular structures in crystals on parallel stacking interactions between pyridine molecules.

    PubMed

    Janjić, Goran V; Ninković, Dragan B; Zarić, Snezana D

    2013-08-01

    Parallel stacking interactions between pyridines in crystal structures and the influence of hydrogen bonding and supramolecular structures in crystals on the geometries of interactions were studied by analyzing data from the Cambridge Structural Database (CSD). In the CSD 66 contacts of pyridines have a parallel orientation of molecules and most of these pyridines simultaneously form hydrogen bonds (44 contacts). The geometries of stacked pyridines observed in crystal structures were compared with the geometries obtained by calculations and explained by supramolecular structures in crystals. The results show that the mean perpendicular distance (R) between pyridine rings with (3.48 Å) and without hydrogen bonds (3.62 Å) is larger than that calculated, because of the influence of supramolecular structures in crystals. The pyridines with hydrogen bonds show a pronounced preference for offsets of 1.25-1.75 Å, close to the position of the calculated minimum (1.80 Å). However, stacking interactions of pyridines without hydrogen bonds do not adopt values at or close to that of the calculated offset. This is because stacking interactions of pyridines without hydrogen bonds are less strong, and they are more susceptible to the influence of supramolecular structures in crystals. These results show that hydrogen bonding and supramolecular structures have an important influence on the geometries of stacked pyridines in crystals.

  5. Oxyfunctionalization of pyridine derivatives using whole cells of Burkholderia sp. MAK1

    PubMed Central

    Stankevičiūtė, Jonita; Vaitekūnas, Justas; Petkevičius, Vytautas; Gasparavičiūtė, Renata; Tauraitė, Daiva; Meškys, Rolandas

    2016-01-01

    Pyridinols and pyridinamines are important intermediates with many applications in chemical industry. The pyridine derivatives are in great demand as synthons for pharmaceutical products. Moreover, pyridines are used either as biologically active substances or as building blocks for polymers with unique physical properties. Application of enzymes or whole cells is an attractive strategy for preparation of hydroxylated pyridines since the methods for chemical synthesis of pyridinols, particularly aminopyridinols, are usually limited or inefficient. Burkholderia sp. MAK1 (DSM102049), capable of using pyridin-2-ol as the sole carbon and energy source, was isolated from soil. Whole cells of Burkholderia sp. MAK1 were confirmed to possess a good ability to convert different pyridin-2-amines and pyridin-2-ones into their 5-hydroxy derivatives. Moreover, several methylpyridines as well as methylated pyrazines were converted to appropriate N-oxides. In conclusion, regioselective oxyfunctionalization of pyridine derivatives using whole cells of Burkholderia sp. MAK1 is a promising method for the preparation of various pyridin-5-ols and pyridin-N-oxides. PMID:27982075

  6. Competition for electrons between pyridine and quinoline during their simultaneous biodegradation.

    PubMed

    Xu, Hua; Sun, Weihua; Yan, Ning; Li, Danni; Wang, Xueqi; Yu, Tingting; Zhang, Yongming; Rittmann, Bruce E

    2017-09-18

    Biodegradation of pyridine and quinoline is initiated with mono-oxygenation reactions that require an intracellular electron donor. Simultaneous biodegradation of both substrates should set up competition for the intracellular electron donor that may inhibit one or more of the mono-oxygenation steps. An internal circulation baffled biofilm reactor (ICBBR) was used to evaluate the impacts of competition during pyridine and quinoline biodegradation. Compared with independent biodegradation, pyridine and quinoline removal rates were slowed when biodegraded simultaneously, although the pyridine removal rate decreased more than for quinoline. The first mono-oxygenation of quinoline (to 2-hydroxyquinoline) always was faster than the first mono-oxygenation of pyridine (to 2-hydroxypyridine), and the difference was accentuated with pyridine and quinoline which were biodegraded simultaneously due to the competition for intracellular electron donor. Competition also existed between the second mono-oxygenations, and the removal rate of 2-hydroxypyridine was faster than the rate for 2-hydroxyquinoline, even though the rate was faster for quinoline than pyridine. Adding an exogenous electron donor accelerated all mono-oxygenations in proportion to the amount of donor added, but the increments were greater for quinoline due to its higher affinity for intracellular electron donors than pyridine. When actual coking wastewater was used as the background matrix, removals of pyridine and quinoline exhibited the same competitive trends.

  7. Biodegradation of pyridine by the new bacterial isolates S. putrefaciens and B. sphaericus.

    PubMed

    Mathur, Anil Kumar; Majumder, C B; Chatterjee, Shamba; Roy, Partha

    2008-09-15

    In this study, two bacterial strains capable of utilizing pyridine as a sole carbon source were isolated from biofilters. Based on the biochemical test, the organisms were identified as Shewanella putrefaciens and Bacillus sphaericus. In liquid cultures, S. putrefaciens and B. sphaericus degraded pyridine quite effectively up to 500 mg L(-1). S. putrefaciens degrades 500 mg L(-1) of pyridine completely within 140 h, whereas the B. sphaericus degrades 500 mg L(-1) of pyridine only nearly 75% and takes a longer duration of 150 h. S. putrefaciens used pyridine as sole carbon and energy source better than B. sphaericus. Monod's and Haldane's inhibitory growth models were used to obtain maximum specific growth rate (micro(max)), half saturation (K(s)) and substrate inhibition (K(i)) constant for pyridine by using S. putrefaciens and B. sphaericus. The high value of K(i) for S. putrefaciens than B. sphaericus indicates that the inhibition effect can be observed only in a high concentration range. The S. putrefaciens degrades pyridine with a faster rate than B. sphaericus. S. putrefaciens can be used effectively for the treatment of pyridine bearing wastewater and as an inoculum in a biofilter treating pyridine-laden gas.

  8. Anaerobic and aerobic degradation of pyridine by a newly isolated denitrifying bacterium.

    PubMed Central

    Rhee, S K; Lee, G M; Yoon, J H; Park, Y H; Bae, H S; Lee, S T

    1997-01-01

    New denitrifying bacteria that could degrade pyridine under both aerobic and anaerobic conditions were isolated from industrial wastewater. The successful enrichment and isolation of these strains required selenite as a trace element. These isolates appeared to be closely related to Azoarcus species according to the results of 16S rRNA sequence analysis. An isolated strain, pF6, metabolized pyridine through the same pathway under both aerobic and anaerobic conditions. Since pyridine induced NAD-linked glutarate-dialdehyde dehydrogenase and isocitratase activities, it is likely that the mechanism of pyridine degradation in strain pF6 involves N-C-2 ring cleavage. Strain pF6 could degrade pyridine in the presence of nitrate, nitrite, and nitrous oxide as electron acceptors. In a batch culture with 6 mM nitrate, degradation of pyridine and denitrification were not sensitively affected by the redox potential, which gradually decreased from 150 to -200 mV. In a batch culture with the nitrate concentration higher than 6 mM, nitrite transiently accumulated during denitrification significantly inhibited cell growth and pyridine degradation. Growth yield on pyridine decreased slightly under denitrifying conditions from that under aerobic conditions. Furthermore, when the pyridine concentration used was above 12 mM, the specific growth rate under denitrifying conditions was higher than that under aerobic conditions. Considering these characteristics, a newly isolated denitrifying bacterium, strain pF6, has advantages over strictly aerobic bacteria in field applications. PMID:9212408

  9. Exo conformers of N-(pyridin-2-yl)- and N-(pyridin-3-yl)norbornene-5,6-dicarboximide crystals.

    PubMed

    Vazquez-Vuelvas, Oscar F; Hernández-Madrigal, Julia V; Pineda-Contreras, Armando; Hernández-Ortega, Simón; Reyes-Martínez, Reyna; Morales-Morales, David

    2015-03-01

    Two isomeric pyridine-substituted norbornenedicarboximide derivatives, namely N-(pyridin-2-yl)-exo-norbornene-5,6-dicarboximide, (I), and N-(pyridin-3-yl)-exo-norbornene-5,6-dicarboximide, (II), both C(14)H(12)N(2)O(4), have been crystallized and their structures unequivocally determined by single-crystal X-ray diffraction. The molecules consist of norbornene moieties fused to a dicarboximide ring substituted at the N atom by either pyridin-2-yl or pyridin-3-yl in an anti configuration with respect to the double bond, thus affording exo isomers. In both compounds, the asymmetric unit consists of two independent molecules (Z' = 2). In compound (I), the pyridine rings of the two independent molecules adopt different conformations, i.e. syn and anti, with respect to the methylene bridge. The intermolecular contacts of (I) are dominated by C-H...O interactions. In contrast, in compound (II), the pyridine rings of both molecules have an anti conformation and the two independent molecules are linked by carbonyl-carbonyl interactions, as well as by C-H...O and C-H...N contacts.

  10. Fast Reactivity of Cyclic Nitrone-Calix[4]pyrrole Conjugate with Superoxide Radical Anion: Theoretical and Experimental Studies1

    PubMed Central

    Kim, Shang-U; Liu, Yangping; Nash, Kevin M.; Zweier, Jay L.; Rockenbauer, Antal; Villamena, Frederick A.

    2010-01-01

    Nitrone spin traps have been employed as probes for the identification of transient radical species in chemical and biological systems using electron paramagnetic resonance (EPR) spectroscopy, and have found pharmacological activity against oxidative stress-mediated diseases. Since superoxide radical anion (O2•−) is a major precursor to most reactive oxygen species and that calix[4]pyrroles have shown to exhibit high affinity to anions, cyclic nitrone conjugate of calix[4]pyrrole (CalixMPO) was designed, synthesized, and characterized. Computational studies at the PCM/B3LYP/6-31+G(d,p)//B3LYP/6-31G(d) suggest a pendant-type linkage between the calix[4]pyrrole and the nitrone to be the most efficient design for spin trapping of O2•−, giving exoergic reaction enthalpies (ΔH298K,aq) and free energies (ΔG298K,aq) of -16.9 and -2.1 kcal/mol, respectively. 1H NMR study revealed solvent-dependent conformational changes in CalixMPO leading to changes in electronic properties of the nitronyl group upon H-bonding with the pyrrole groups as also confirmed by calculations. CalixMPO spin trapping of O2•− exhibited distinctive EPR spectra. Kinetic analysis of O2•− adduct formation and decay in polar aprotic solvents using UV-vis stopped-flow and EPR method gave larger trapping rate constant for CalixMPO and longer half-life for its O2•− adduct compared to the commonly used nitrones. The unusually high reactivity of CalixMPO to O2•− was rationalized to be due to the synergy between α- and electrostatic effects by the calix[4]pyrrole moiety on the O2•− and nitrone, respectively. This work demonstrates for the first time the application of an anion receptor for the detection of one the most important radical intermediates in biological and chemical systems (i.e., O2•−). PMID:21070040

  11. Brönsted Acid-Catalyzed One-Pot Synthesis of Indoles from o-Aminobenzyl Alcohols and Furans

    PubMed Central

    Kuznetsov, Alexey; Makarov, Anton; Rubtsov, Alexandr E.; Butin, Alexander V.; Gevorgyan, Vladimir

    2013-01-01

    Brönsted acid-catalyzed one-pot synthesis of indoles from o-aminobenzyl alcohols and furans has been developed. This method operates via the in situ formation of aminobenzylfuran, followed by its recyclization into the indole core. The method proved to be efficient for substrates possessing different functional groups, including -OMe, -CO2Cy, and -Br. The resulting indoles can easily be transformed into diverse scaffolds, including 2,3- and 1,2-fused indoles, and indole possessing an α,β-unsaturated ketone moiety at the C-2 position. PMID:24255969

  12. Unconventional hydrogen bonding to organic ions in the gas phase: stepwise association of hydrogen cyanide with the pyridine and pyrimidine radical cations and protonated pyridine.

    PubMed

    Hamid, Ahmed M; El-Shall, M Samy; Hilal, Rifaat; Elroby, Shaaban; Aziz, Saadullah G

    2014-08-07

    Equilibrium thermochemical measurements using the ion mobility drift cell technique have been utilized to investigate the binding energies and entropy changes for the stepwise association of HCN molecules with the pyridine and pyrimidine radical cations forming the C5H5N(+·)(HCN)n and C4H4N2 (+·)(HCN)n clusters, respectively, with n = 1-4. For comparison, the binding of 1-4 HCN molecules to the protonated pyridine C5H5NH(+)(HCN)n has also been investigated. The binding energies of HCN to the pyridine and pyrimidine radical cations are nearly equal (11.4 and 12.0 kcal/mol, respectively) but weaker than the HCN binding to the protonated pyridine (14.0 kcal/mol). The pyridine and pyrimidine radical cations form unconventional carbon-based ionic hydrogen bonds with HCN (CH(δ+)⋯NCH). Protonated pyridine forms a stronger ionic hydrogen bond with HCN (NH(+)⋯NCH) which can be extended to a linear chain with the clustering of additional HCN molecules (NH(+)⋯NCH··NCH⋯NCH) leading to a rapid decrease in the bond strength as the length of the chain increases. The lowest energy structures of the pyridine and pyrimidine radical cation clusters containing 3-4 HCN molecules show a strong tendency for the internal solvation of the radical cation by the HCN molecules where bifurcated structures involving multiple hydrogen bonding sites with the ring hydrogen atoms are formed. The unconventional H-bonds (CH(δ+)⋯NCH) formed between the pyridine or the pyrimidine radical cations and HCN molecules (11-12 kcal/mol) are stronger than the similar (CH(δ+)⋯NCH) bonds formed between the benzene radical cation and HCN molecules (9 kcal/mol) indicating that the CH(δ+) centers in the pyridine and pyrimidine radical cations have more effective charges than in the benzene radical cation.

  13. Synthesis of tricyclic indole-2-carboxylic [correction of caboxylic] acids as potent NMDA-glycine antagonists.

    PubMed

    Katayama, S; Ae, N; Nagata, R

    2001-05-18

    The practical synthesis of a series of tricyclic indole-2-carboxylic acids, 7-chloro-3-arylaminocarbonylmethyl-1,3,4,5-tetrahydrobenz[cd]indole-2-carboxylic acids, as a new class of potent NMDA-glycine antagonists is described. The synthetic route to the key intermediate 12a comprises a regioselective iodination of 4-chloro-2-nitrotoluene, modified Reissert indole synthesis, Jeffery's Heck-type reaction with allyl alcohol, Wittig-Horner-Emmons reaction, and iodination at the indole C-3 position. The key step in the route is an intramolecular cyclization of 12a to give the tricyclic indole structure. Two methods of cyclization, (1) an intramolecular radical cyclization of 12a and (2) a sequence of intramolecular Heck reaction of 12a followed by a 1,4-reduction, were performed. The resulting tricyclic indole diester 13a was selectively hydrolyzed to afford the desired tricyclic indole monocarboxylic acid 16 on a multihundred gram scale without any chromatographic purifications. Optical resolution of 16 to (-)-isomer 17 and (+)-isomer 18 was carried out, and the resulting isomers were derivatized, respectively. Evaluation of the optically active derivatives for affinity to the NMDA-glycine binding site using the radio ligand binding assay with [(3)H]-5,7-dichlorokynurenic acid revealed that the derivatives of (-)-isomer 17 were more potent than the others and that especially substituted anilide (-)-isomer 24 (K(i) = 0.8 nM) showed high affinity.

  14. Asymmetric distribution of glucose and indole-3-acetyl-myo-inositol in geostimulated Zea mays seedlings

    NASA Technical Reports Server (NTRS)

    Momonoki, Y. S.; Bandurski, R. S. (Principal Investigator)

    1988-01-01

    Indole-3-acetyl-myo-inositol occurs in both the kernel and vegetative shoot of germinating Zea mays seedlings. The effect of a gravitational stimulus on the transport of [3H]-5-indole-3-acetyl-myo-inositol and [U-14C]-D-glucose from the kernel to the seedling shoot was studied. Both labeled glucose and labeled indole-3-acetyl-myo-inositol become asymmetrically distributed in the mesocotyl cortex of the shoot with more radioactivity occurring in the bottom half of a horizontally placed seedling. Asymmetric distribution of [3H]indole-3-acetic acid, derived from the applied [3H]indole-3-acetyl-myo-inositol, occurred more rapidly than distribution of total 3H-radioactivity. These findings demonstrate that the gravitational stimulus can induce an asymmetric distribution of substances being transported from kernel to shoot. They also indicate that, in addition to the transport asymmetry, gravity affects the steady state amount of indole-3-acetic acid derived from indole-3-acetyl-myo-inositol.

  15. Asymmetric distribution of glucose and indole-3-acetyl-myo-inositol in geostimulated Zea mays seedlings

    NASA Technical Reports Server (NTRS)

    Momonoki, Y. S.; Bandurski, R. S. (Principal Investigator)

    1988-01-01

    Indole-3-acetyl-myo-inositol occurs in both the kernel and vegetative shoot of germinating Zea mays seedlings. The effect of a gravitational stimulus on the transport of [3H]-5-indole-3-acetyl-myo-inositol and [U-14C]-D-glucose from the kernel to the seedling shoot was studied. Both labeled glucose and labeled indole-3-acetyl-myo-inositol become asymmetrically distributed in the mesocotyl cortex of the shoot with more radioactivity occurring in the bottom half of a horizontally placed seedling. Asymmetric distribution of [3H]indole-3-acetic acid, derived from the applied [3H]indole-3-acetyl-myo-inositol, occurred more rapidly than distribution of total 3H-radioactivity. These findings demonstrate that the gravitational stimulus can induce an asymmetric distribution of substances being transported from kernel to shoot. They also indicate that, in addition to the transport asymmetry, gravity affects the steady state amount of indole-3-acetic acid derived from indole-3-acetyl-myo-inositol.

  16. Indole production provides limited benefit to Escherichia coli during co-culture with Enterococcus faecalis.

    PubMed

    Pringle, Shelly L; Palmer, Kelli L; McLean, Robert J C

    2017-01-01

    Escherichia coli lives in the gastrointestinal tract and elsewhere, where it coexists within a mixed population. Indole production enables E. coli to grow with other gram-negative bacteria as indole inhibits N-acyl-homoserine lactone (AHL) quorum regulation. We investigated whether E. coli indole production enhanced competition with gram-positive Enterococcus faecalis, wherein quorum signaling is mediated by small peptides. During planktonic co-culture with E. faecalis, the fitness and population density of E. coli tnaA mutants (unable to produce indole) equaled or surpassed that of E. coli wt. During biofilm growth, the fitness of both populations of E. coli stabilized around 100 %, whereas the fitness of E. faecalis declined over time to 85-90 %, suggesting that biofilm and planktonic populations have different competition strategies. Media supplementation with indole removed the competitive advantage of E. coli tnaA in planktonic populations but enhanced it in biofilm populations. E. coli wt and tnaA showed similar growth in Luria-Bertani (LB) broth. However, E. coli growth was inhibited in the presence of filter-sterilized spent LB from E. faecalis, with inhibition being enhanced by indole. Similarly, there was also an inhibition of E. faecalis growth by proteinaceous components (likely bacteriocins) from spent culture media from both E. coli strains. We conclude that E. coli indole production is not a universal competition strategy, but rather works against gram-negative, AHL-producing bacteria.

  17. Efficient Synthesis of Peptide and Protein Functionalized Pyrrole-Imidazole Polyamides Using Native Chemical Ligation.

    PubMed

    Janssen, Brian M G; van Ommeren, Sven P F I; Merkx, Maarten

    2015-06-04

    The advancement of DNA-based bionanotechnology requires efficient strategies to functionalize DNA nanostructures in a specific manner with other biomolecules, most importantly peptides and proteins. Common DNA-functionalization methods rely on laborious and covalent conjugation between DNA and proteins or peptides. Pyrrole-imidazole (Py-Im) polyamides, based on natural minor groove DNA-binding small molecules, can bind to DNA in a sequence specific fashion. In this study, we explore the use of Py-Im polyamides for addressing proteins and peptides to DNA in a sequence specific and non-covalent manner. A generic synthetic approach based on native chemical ligation was established that allows efficient conjugation of both peptides and recombinant proteins to Py-Im polyamides. The effect of Py-Im polyamide conjugation on DNA binding was investigated by Surface Plasmon Resonance (SPR). Although the synthesis of different protein-Py-Im-polyamide conjugates was successful, attenuation of DNA affinity was observed, in particular for the protein-Py-Im-polyamide conjugates. The practical use of protein-Py-Im-polyamide conjugates for addressing DNA structures in an orthogonal but non-covalent manner, therefore, remains to be established.

  18. Configurational Analysis of Tetracyclic Dimeric Pyrrole-Imidazole Alkaloids using a Floating Chirality Approach

    PubMed Central

    Köck, Matthias; Schmidt, Gesine; Seiple, Ian B.; Baran, Phil S.

    2012-01-01

    The structure elucidation of the palau'amine congener tetrabromostyloguanidine (1), which used interproton distances from ROESY spectra as restraints in a computational approach, the so-called fc-rDG/DDD method, led to a revision of the relative configuration of palau'amine (2) and its congeners in 2007. The recent total synthesis of (±)-palau'amine (2) subsequently confirmed the computed structural revision of the relative configuration. In order to test a broader application range of the fc-rDG/DDD method, the present study investigated two additional dimeric pyrrole-imidazole alkaloids, axinellamine A (3) and 3,7-epi-massadine chloride (4). These calculations allowed the simultaneous assignment of the relative configuration for all eight stereogenic centers of compounds 3 and 4 without using any information from the reported configurations. In contrast to the palau'amine congeners, the fc-rDG/DDD method confirmed the relative configuration originally described for axinellamine A (3) and 3,7-epi-massadine chloride (4). PMID:22332969

  19. A concise synthesis of (+)-batzelladine B from simple pyrrole-based starting materials.

    PubMed

    Parr, Brendan T; Economou, Christos; Herzon, Seth B

    2015-09-24

    Alkaloids, secondary metabolites that contain basic nitrogen atoms, are some of the most well-known biologically active natural products in chemistry and medicine. Although efficient laboratory synthesis of alkaloids would enable the study and optimization of their biological properties, their preparation is often complicated by the basicity and nucleophilicity of nitrogen, its susceptibility to oxidation, and its ability to alter reaction outcomes in unexpected ways--for example, through stereochemical instability and neighbouring group participation. Efforts to address these issues have led to the invention of a large number of protecting groups that temper the reactivity of nitrogen; however, the use of protecting groups typically introduces additional steps and obstacles into the synthetic route. Alternatively, the use of aromatic nitrogen heterocycles as synthetic precursors can attenuate the reactivity of nitrogen and streamline synthetic strategies. Here we use such an approach to achieve a synthesis of the complex anti-HIV alkaloid (+)-batzelladine B in nine steps (longest linear sequence) from simple pyrrole-based starting materials. The route uses several key transformations that would be challenging or impossible to implement using saturated nitrogen heterocycles and highlights some of the advantages of beginning with aromatic reagents.

  20. Configurational analysis of tetracyclic dimeric pyrrole-imidazole alkaloids using a floating chirality approach.

    PubMed

    Köck, Matthias; Schmidt, Gesine; Seiple, Ian B; Baran, Phil S

    2012-02-24

    The structure elucidation of the palau'amine congener tetrabromostyloguanidine (1), which used interproton distances from ROESY spectra as restraints in a computational approach, the so-called fc-rDG/DDD method, led to a revision of the relative configuration of palau'amine (2) and its congeners in 2007. The recent total synthesis of (±)-palau'amine (2) subsequently confirmed the computed structural revision of the relative configuration. In order to test a broader application range of the fc-rDG/DDD method, the present study investigated two additional dimeric pyrrole-imidazole alkaloids, axinellamine A (3) and 3,7-epi-massadine chloride (4). These calculations allowed the simultaneous assignment of the relative configuration for all eight stereogenic centers of compounds 3 and 4 without using any information from the reported configurations. In contrast to the palau'amine congeners, the fc-rDG/DDD method confirmed the relative configuration originally described for axinellamine A (3) and 3,7-epi-massadine chloride (4).

  1. Pyrrole-indolinone SU11652 targets the nucleoside diphosphate kinase from Leishmania parasites.

    PubMed

    Vieira, Plínio Salmazo; Souza, Tatiana de Arruda Campos Brasil; Honorato, Rodrigo Vargas; Zanphorlin, Letícia Maria; Severiano, Kelven Ulisses; Rocco, Silvana Aparecida; de Oliveira, Arthur Henrique Cavalcante; Cordeiro, Artur Torres; Oliveira, Paulo Sérgio Lopes; de Giuseppe, Priscila Oliveira; Murakami, Mário Tyago

    2017-07-01

    Nucleoside diphosphate kinases (NDKs) are key enzymes in the purine-salvage pathway of trypanosomatids and have been associated with the maintenance of host-cell integrity for the benefit of the parasite, being potential targets for rational drug discovery and design. The NDK from Leishmania major (LmNDK) and mutants were expressed and purified to homogeneity. Thermal shift assays were employed to identify potential inhibitors for LmNDK. Calorimetric experiments, site-directed mutagenesis and molecular docking analysis were performed to validate the interaction and to evaluate the structural basis of ligand recognition. Furthermore, the anti-leishmanial activity of the newly identified and validated compound was tested in vitro against different Leishmania species. The molecule SU11652, a Sunitinib analog, was identified as a potential inhibitor for LmNDK and structural studies indicated that this molecule binds to the active site of LmNDK in a similar conformation to nucleotides, mimicking natural substrates. Isothermal titration calorimetry experiments combined with site-directed mutagenesis revealed that the residues H50 and H117, considered essential for catalysis, play an important role in ligand binding. In vitro cell studies showed that SU11652 had similar efficacy to Amphotericin b against some Leishmania species. Together, our results indicate the pyrrole-indolinone SU11652 as a promising scaffold for the rational design of new drugs targeting the enzyme NDK from Leishmania parasites. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Novel Pt(II) complexes containing pyrrole oxime; synthesis, characterization and DNA binding studies

    NASA Astrophysics Data System (ADS)

    Erdogan, Deniz Altunoz; Özalp-Yaman, Şeniz

    2014-05-01

    Since the discovery of anticancer activity and subsequent clinical success of cisplatin (cis-[PtCl2(NH3)2]), platinum-based compounds have since been widely synthesized and studied as potential chemotherapeutic agents. In this sense, three novel nuclease active Pt(II) complexes with general formula; [Pt(NH3)Cl(L)] (1), [Pt(L)2] (2), and K[PtCl2(L)] (3) in which L is 1-H-pyrrole-2-carbaldehyde oxime were synthesized. Characterization of complexes was performed by elemental analysis, FT-IR, 1H NMR and mass spectroscopy measurements. Interaction of complexes (1-3) with calf thymus deoxyribonucleic acid (ct-DNA) was investigated by using electrochemical, spectroelectrochemical methods and cleavage studies. The hyperchromic change in the electronic absorption spectrum of the Pt(II) complexes indicates an electrostatic interaction between the complexes and ct-DNA. Binding constant values between 4.42 × 103 and 5.09 × 103 M-1 and binding side size values between 2 and 3 base pairs were determined from cyclic voltammetry (CV) and differential pulse voltammetry (DPV) studies.

  3. Pharmacological evaluation of anti-inflammatory pyrrole-acetic acid derivative eye drops.

    PubMed

    Bucolo, C; Spadaro, A

    1997-08-01

    The effects of mucoadhesive eye drops containing a pyrrole-acetic acid derivative (tolmetin) at 0.5% concentration on ocular inflammation produced by sodium arachidonate in the rabbit's eye were evaluated. Furthermore, the bioavailability of the mucoadhesive formulation in the aqueous humor against an aqueous-based solution was compared. Tolmetin eye drops significantly reduced the signs of ocular inflammation elicited by sodium arachidonate on conjunctiva and iris. Tolmetin treatment significantly reduced the levels of prostaglandin E2, polymorphonuclear leukocytes and protein concentration in aqueous samples obtained from the eyes treated with arachidonate. The de novo production of prostaglandin E2 by corneas obtained from rabbits sacrificed 2 hours after arachidonate instillation were significantly higher in samples taken from controls than in corneas obtained from the eyes treated with tolmetin eye drops. Furthermore, the drug treatment significantly reduced the rise in intraocular pressure arachidonate-induced. The mucoadhesive formulation showed a higher bioavailability in aqueous humor compared to the aqueous-based solution both in the uninflamed and in the inflamed rabbit eyes.

  4. A concise synthesis of (+)-batzelladine B from simple pyrrole-based starting materials

    PubMed Central

    Parr, Brendan T.; Economou, Christos; Herzon, Seth B.

    2015-01-01

    Alkaloids, secondary metabolites that contain basic nitrogen atoms, are some of the most well-known biologically active natural products in chemistry and medicine1. Although the efficient laboratory syntheses of alkaloids would enable researchers to study and optimize their biological properties,2 the basicity and nucleophilicity of nitrogen, its susceptibility to oxidation, and its ability to alter reaction outcomes in unexpected ways – for example, through stereochemical instability and neighboring group participation – complicates their preparation in the laboratory. Efforts to address these issues have led to the invention of a large number of protecting groups that temper the reactivity of nitrogen3; however, the use of protecting groups typically introduce additional steps and obstacles into the synthetic route. Alternatively, the use of aromatic nitrogen heterocycles as synthetic precursors can attenuate the reactivity of nitrogen and streamline synthetic strategies4. In this manuscript, we use such an approach to achieve a synthesis of the complex anti-HIV alkaloid (+)-batzelladine B in nine steps (longest-linear sequence) from simple pyrrole-based starting materials. The route employs several key transformations that would be challenging or impossible to implement using saturated nitrogen heterocycles and highlights some of the advantages conferred by the use of aromatic starting materials. PMID:26375010

  5. A concise synthesis of (+)-batzelladine B from simple pyrrole-based starting materials

    NASA Astrophysics Data System (ADS)

    Parr, Brendan T.; Economou, Christos; Herzon, Seth B.

    2015-09-01

    Alkaloids, secondary metabolites that contain basic nitrogen atoms, are some of the most well-known biologically active natural products in chemistry and medicine. Although efficient laboratory synthesis of alkaloids would enable the study and optimization of their biological properties, their preparation is often complicated by the basicity and nucleophilicity of nitrogen, its susceptibility to oxidation, and its ability to alter reaction outcomes in unexpected ways--for example, through stereochemical instability and neighbouring group participation. Efforts to address these issues have led to the invention of a large number of protecting groups that temper the reactivity of nitrogen; however, the use of protecting groups typically introduces additional steps and obstacles into the synthetic route. Alternatively, the use of aromatic nitrogen heterocycles as synthetic precursors can attenuate the reactivity of nitrogen and streamline synthetic strategies. Here we use such an approach to achieve a synthesis of the complex anti-HIV alkaloid (+)-batzelladine B in nine steps (longest linear sequence) from simple pyrrole-based starting materials. The route uses several key transformations that would be challenging or impossible to implement using saturated nitrogen heterocycles and highlights some of the advantages of beginning with aromatic reagents.

  6. The 8-Pyrrole-Benzothiazinones Are Noncovalent Inhibitors of DprE1 from Mycobacterium tuberculosis.

    PubMed

    Makarov, Vadim; Neres, João; Hartkoorn, Ruben C; Ryabova, Olga B; Kazakova, Elena; Šarkan, Michal; Huszár, Stanislav; Piton, Jérémie; Kolly, Gaëlle S; Vocat, Anthony; Conroy, Trent M; Mikušová, Katarína; Cole, Stewart T

    2015-08-01

    8-Nitro-benzothiazinones (BTZs), such as BTZ043 and PBTZ169, inhibit decaprenylphosphoryl-β-d-ribose 2'-oxidase (DprE1) and display nanomolar bactericidal activity against Mycobacterium tuberculosis in vitro. Structure-activity relationship (SAR) studies revealed the 8-nitro group of the BTZ scaffold to be crucial for the mechanism of action, which involves formation of a semimercaptal bond with Cys387 in the active site of DprE1. To date, substitution of the 8-nitro group has led to extensive loss of antimycobacterial activity. Here, we report the synthesis and characterization of the pyrrole-benzothiazinones PyrBTZ01 and PyrBTZ02, non-nitro-benzothiazinones that retain significant antimycobacterial activity, with MICs of 0.16 μg/ml against M. tuberculosis. These compounds inhibit DprE1 with 50% inhibitory concentration (IC50) values of <8 μM and present favorable in vitro absorption-distribution-metabolism-excretion/toxicity (ADME/T) and in vivo pharmacokinetic profiles. The most promising compound, PyrBTZ01, did not show efficacy in a mouse model of acute tuberculosis, suggesting that BTZ-mediated killing through DprE1 inhibition requires a combination of both covalent bond formation and compound potency. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  7. Vibrational overtone spectroscopy and intramolecular dynamics of C-H stretches in pyrrole

    NASA Astrophysics Data System (ADS)

    Portnov, Alexander; Epshtein, Michael; Rosenwaks, Salman; Bar, Ilana

    2013-05-01

    Room-temperature photoacoustic spectra and jet-cooled action spectra of the regions of the first and second C-H stretch overtones of pyrrole were measured with the goal of gaining new insight on the vibrational patterns and the intramolecular energy flow out of the initially excited vibrational states. The rotational cooling of the action spectra helped in observing hitherto unresolved features, assisting determination of the existing multiple bands and their positions in each region. These bands were analyzed by building vibrational Hamiltonian matrices related to a simplified joint local-mode/normal-mode (LM/NM) model, accounting for two types of C-H stretches and their Fermi resonances with the CCH deformation modes. The diagonalization of the LM/NM vibrational Hamiltonians and the fitting of the eigenvalues to the band positions revealed model parameters, enabling assignment of the observed bands. The time dependences of the survival probabilities of the C-H stretches in the region of the first and second overtones, deduced from the vibrational Hamiltonian, show quantum beats due to the couplings to the deformations and decays driven by weaker interactions to the bath states. The C-H stretches, although somewhat lower in energy, show stronger coupling than the N-H stretches.

  8. Facile and controllable electrochemical fabrication of cell-adhesive polypyrrole electrodes using pyrrole-RGD peptides.

    PubMed

    Jang, Lindy K; Kim, Semin; Seo, Jiwon; Lee, Jae Young

    2017-10-11

    Electrically conductive polymers, such as polypyrrole (PPy), have been widely used for the fabrication of various biosensors and tissue engineering scaffolds. For their biologically relevant applications, conductive biomaterials capable of intimate cellular interactions are highly desired. However, conventional methods to incorporate biomolecules into conductive polymers do not offer fine and easy control over the surface density of the biomolecules and/or their stability. We present a novel method to electrochemically immobilize cell adhesive Arg-Gly-Asp (RGD) ligands on PPy electrode surfaces with a simple control over the peptide surface density by varying the electrodeposition time. Synthesized pyrrole-GGGRGDS conjugates were electrochemically incorporated onto the surfaces of PPy-coated electrodes. The electrochemical impedances of the RGD-grafted PPy electrodes were not significantly different from the unmodified PPy films. Time-of-flight secondary-ion mass spectroscopy confirmed the presence of the RGD motif on the surface of the modified electrodes. In vitro studies with human mesenchymal stem cells (hMSCs) showed higher adhesion and faster proliferation of hMSCs on the PPy with a higher RGD density. This facile electrochemical modification of electrode surfaces allowed for a good control over the peptide surface density and cellular interactions and will benefit the fabrication of cell-interactive scaffolds or bio-electrodes. © 2017 IOP Publishing Ltd.

  9. Selective Anion Binding by a Cofacial Binuclear Zinc Complex of a Schiff-Base Pyrrole Macrocycle

    PubMed Central

    Devoille, Aline M. J.; Richardson, Patricia; Bill, Nathan; Sessler, Jonathan L.; Love, Jason B.

    2011-01-01

    The synthesis of the new cofacial binuclear zinc complex [Zn2(L)] of a Schiff-base pyrrole macrocycle is reported. It was discovered that the binuclear microenvironment between the two metals of [Zn2(L)] is suited for the encapsulation of anions, leading to the formation of [K(THF)6][Zn2(μ-Cl)(L)].2THF and [Bun4N][Zn2(μ-OH)(L)] which were characterized by X-ray crystallography. Unusually obtuse Zn-X-Zn angles (X=Cl: 150.54(9)° and OH: 157.4(3)°) illustrate the weak character of these interactions and the importance of the cleft pre-organization to stabilize the host. In the absence of added anion, aggregation of [Zn2(L)] was inferred and investigated by successive dilutions and by the addition of coordinating solvents to [Zn2(L)] solutions using NMR spectroscopy as well as isothermal microcalorimetry (ITC). On anion addition, evidence for de-aggregation of [Zn2(L)], combined with the formation of the 1:1 host-guest complex, was observed by NMR spectroscopy and ITC titrations. Furthermore, [Zn2(L)] binds to Cl− selectively in THF as deduced from the ITC analyses, while other halides induce only de-aggregation. These conclusions were reinforced by DFT calculations, which indicated that the binding energies of OH− and Cl− were significantly greater than for the other halides. PMID:21391550

  10. Investigation of irradiated 1H-Benzo[b]pyrrole by ESR, thermal methods and learning algorithm

    NASA Astrophysics Data System (ADS)

    Algul, Gulay; Ceylan, Yusuf; Usta, Keziban; Yumurtaci Aydogmus, Hacer; Usta, Ayhan; Asik, Biray

    2016-05-01

    1H-Benzo[b]pyrrole samples were irradiated in the air with gamma source at 0.969 kGy per hour at room temperature for 24, 48 and 72 h. After irradiation, electron spin resonance, thermogravimetry analysis (TGA) and differential thermal analysis (DTA) measurements were immediately carried out on the irradiated and unirradiated samples. The ESR measurements were performed between 320 and 400 K. ESR spectra were recorded from the samples irradiated for 48 and 72 h. The obtained spectra were observed to be dependent on temperature. Two radical-type centres were detected on the sample. Detected radiation-induced radicals were attributed to R-+•NH and R=•CC2H2. The g-values and hyperfine constants were calculated by means of the experimental spectra. It was also determined from TGA spectrum that both the unirradiated and irradiated samples were decomposed at one step with the rising temperature. Moreover, a theoretical study was presented. Success of the machine learning methods was tested. It was found that bagging techniques, which are widely used in the machine learning literature, could optimise prediction accuracy noticeably.

  11. Flexible electrochemical capacitors based on polypyrrole/carbon fibers via chemical polymerization of pyrrole vapor

    NASA Astrophysics Data System (ADS)

    Yuan, Wei; Han, Gaoyi; Xiao, Yaoming; Chang, Yunzhen; Liu, Cuixian; Li, Miaoyu; Li, Yanping; Zhang, Ying

    2016-07-01

    Polypyrrole (PPy) has been deposited on the carbon fibers (CFs) via chemical oxidation of monomer vapor strategy, during which FeCl3·6H2O in acetonitrile adsorbed on CFs acts as oxidant to polymerize the pyrrole vapor. The morphologies and capacitive properties of the PPy deposited on CFs (PPy/CFs) are strongly influenced by the concentration of oxidant used in the process. The assembled flexible capacitors by using PPy/CFs as electrodes and LiCl/polyvinyl alcohol as gel electrolyte have been evaluated by cyclic voltammetry, galvanostatic charge/discharge and electrochemical impedance spectroscopy. The results show that the composites of PPy/CFs prepared by using 350 mg mL-1 FeCl3·6H2O as oxidant (PPy/CFs-350) exhibit relatively higher specific capacitance and good rate capability. Compared with PPy/CFs prepared by electrochemical deposition (retaining 5% of the initial capacitance), the PPy/CFs prepared by chemically polymerizing monomer vapor shows excellent stability (retaining 85% of initial capacitance after 5000 cycles). Furthermore, cells fabricated by PPy/CFs show a fairly good performance under various bending states, three cells of PPy/CFs-350 connected in series can light up a light emitting diode with a voltage threshold of about 2.5 V for approximate 10 min after being charged for about 3 min, revealing the potential of the cells' practical applications.

  12. Evaluation of the pyrrole insecticide chlorfenapyr against pyrethroid resistant and susceptible Anopheles funestus (Diptera: Culicidae).

    PubMed

    Oliver, S V; Kaiser, M L; Wood, O R; Coetzee, M; Rowland, M; Brooke, B D

    2010-01-01

    To evaluate the pyrrole insecticide chlorfenapyr, which has a novel non-neurotoxic mode of action and is a promising alternative to conventional adulticides, against Anopheles funestus. The toxicity of a range of concentrations of chlorfenapyr against pyrethroid resistant and susceptible laboratory reared southern African An. funestus was assessed using standard WHO protocols and analysed using probit analysis. The pyrethroid resistant strain showed consistently higher LD50 and LD95 values compared to the susceptible strain, but these differences were not statistically significant and the magnitude was twofold at most. The LD50 values recorded for An. funestus are approximately three-fold higher than those reported elsewhere for other species of anopheline. Monooxygenase based pyrethroid resistance in An. funestus does not influence the toxic effect of chlorfenapyr. It is unlikely that such a small decrease in susceptibility of An. funestus to chlorfenapyr relative to other anophelines would have any operational implications. Chlorfenapyr is an important addition to insecticides available for malaria vector control, and could be used as a resistance management tool to either circumvent or slow the development of resistance.

  13. Development of a novel gene silencer pyrrole-imidazole polyamide targeting human connective tissue growth factor.

    PubMed

    Wan, Jian-Xin; Fukuda, Noboru; Ueno, Takahiro; Watanabe, Takayoshi; Matsuda, Hiroyuki; Saito, Kosuke; Nagase, Hiroki; Matsumoto, Yoshiaki; Matsumoto, Koichi

    2011-01-01

    Pyrrole-imidazole (PI) polyamide can bind to specific sequences in the minor groove of double-helical DNA and inhibit transcription of the genes. We designed and synthesized a PI polyamide to target the human connective tissue growth factor (hCTGF) promoter region adjacent to the Smads binding site. Among coupling activators that yield PI polyamides, 1-[bis(dimethylamino)methylene]-5-chloro-1H-benzotriazolium 3-oxide hexafluorophosphate (HCTU) was most effective in total yields of PI polyamides. A gel shift assay showed that a PI polyamide designed specifically for hCTGF (PI polyamide to hCTGF) bound the appropriate double-stranded oligonucleotide. A fluorescein isothiocyanate (FITC)-conjugated PI polyamide to CTGF permeated cell membranes and accumulated in the nuclei of cultured human mesangial cells (HMCs) and remained there for 48 h. The PI polyamide to hCTGF significantly decreased phorbol 12-myristate acetate (PMA)- or transforming growth factor-β1 (TGF-β1)-stimulated luciferase activity of the hCTGF promoter in cultured HMCs. The PI polyamide to hCTGF significantly decreased PMA- or TGF-β1-stimulated expression of hCTGF mRNA in a dose-dependent manner. The PI polyamide to hCTGF significantly decreased PMA- or TGF-β1-stimulated levels of hCTGF protein in HMCs. These results indicate that the developed synthetic PI polyamide to hCTGF could be a novel gene silencer for fibrotic diseases.

  14. Efficient Synthesis of Peptide and Protein Functionalized Pyrrole-Imidazole Polyamides Using Native Chemical Ligation

    PubMed Central

    Janssen, Brian M. G.; van Ommeren, Sven P. F. I.; Merkx, Maarten

    2015-01-01

    The advancement of DNA-based bionanotechnology requires efficient strategies to functionalize DNA nanostructures in a specific manner with other biomolecules, most importantly peptides and proteins. Common DNA-functionalization methods rely on laborious and covalent conjugation between DNA and proteins or peptides. Pyrrole-imidazole (Py–Im) polyamides, based on natural minor groove DNA-binding small molecules, can bind to DNA in a sequence specific fashion. In this study, we explore the use of Py–Im polyamides for addressing proteins and peptides to DNA in a sequence specific and non-covalent manner. A generic synthetic approach based on native chemical ligation was established that allows efficient conjugation of both peptides and recombinant proteins to Py–Im polyamides. The effect of Py–Im polyamide conjugation on DNA binding was investigated by Surface Plasmon Resonance (SPR). Although the synthesis of different protein-Py–Im-polyamide conjugates was successful, attenuation of DNA affinity was observed, in particular for the protein-Py–Im-polyamide conjugates. The practical use of protein-Py–Im-polyamide conjugates for addressing DNA structures in an orthogonal but non-covalent manner, therefore, remains to be established. PMID:26053396

  15. Genomic hallmarks of localized, non-indolent prostate cancer.

    PubMed

    Fraser, Michael; Sabelnykova, Veronica Y; Yamaguchi, Takafumi N; Heisler, Lawrence E; Livingstone, Julie; Huang, Vincent; Shiah, Yu-Jia; Yousif, Fouad; Lin, Xihui; Masella, Andre P; Fox, Natalie S; Xie, Michael; Prokopec, Stephenie D; Berlin, Alejandro; Lalonde, Emilie; Ahmed, Musaddeque; Trudel, Dominique; Luo, Xuemei; Beck, Timothy A; Meng, Alice; Zhang, Junyan; D'Costa, Alister; Denroche, Robert E; Kong, Haiying; Espiritu, Shadrielle Melijah G; Chua, Melvin L K; Wong, Ada; Chong, Taryne; Sam, Michelle; Johns, Jeremy; Timms, Lee; Buchner, Nicholas B; Orain, Michèle; Picard, Valérie; Hovington, Helène; Murison, Alexander; Kron, Ken; Harding, Nicholas J; P'ng, Christine; Houlahan, Kathleen E; Chu, Kenneth C; Lo, Bryan; Nguyen, Francis; Li, Constance H; Sun, Ren X; de Borja, Richard; Cooper, Christopher I; Hopkins, Julia F; Govind, Shaylan K; Fung, Clement; Waggott, Daryl; Green, Jeffrey; Haider, Syed; Chan-Seng-Yue, Michelle A; Jung, Esther; Wang, Zhiyuan; Bergeron, Alain; Dal Pra, Alan; Lacombe, Louis; Collins, Colin C; Sahinalp, Cenk; Lupien, Mathieu; Fleshner, Neil E; He, Housheng H; Fradet, Yves; Tetu, Bernard; van der Kwast, Theodorus; McPherson, John D; Bristow, Robert G; Boutros, Paul C

    2017-01-19

    Prostate tumours are highly variable in their response to therapies, but clinically available prognostic factors can explain only a fraction of this heterogeneity. Here we analysed 200 whole-genome sequences and 277 additional whole-exome sequences from localized, non-indolent prostate tumours with similar clinical risk profiles, and carried out RNA and methylation analyses in a subset. These tumours had a paucity of clinically actionable single nucleotide variants, unlike those seen in metastatic disease. Rather, a significant proportion of tumours harboured recurrent non-coding aberrations, large-scale genomic rearrangements, and alterations in which an inversion repressed transcription within its boundaries. Local hypermutation events were frequent, and correlated with specific genomic profiles. Numerous molecular aberrations were prognostic for disease recurrence, including several DNA methylation events, and a signature comprised of these aberrations outperformed well-described prognostic biomarkers. We suggest that intensified treatment of genomically aggressive localized prostate cancer may improve cure rates.

  16. Biogenetically inspired synthesis and skeletal diversification of indole alkaloids

    NASA Astrophysics Data System (ADS)

    Mizoguchi, Haruki; Oikawa, Hideaki; Oguri, Hiroki

    2014-01-01

    To access architecturally complex natural products, chemists usually devise a customized synthetic strategy for constructing a single target skeleton. In contrast, biosynthetic assembly lines often employ divergent intramolecular cyclizations of a polyunsaturated common intermediate to produce diverse arrays of scaffolds. With the aim of integrating such biogenetic strategies, we show the development of an artificial divergent assembly line generating unprecedented numbers of scaffold variations of terpenoid indole alkaloids. This approach not only allows practical access to multipotent intermediates, but also enables systematic diversification of skeletal, stereochemical and functional group properties without structural simplification of naturally occurring alkaloids. Three distinct modes of [4+2] cyclizations and two types of redox-mediated annulations provided divergent access to five skeletally distinct scaffolds involving iboga-, aspidosperma-, andranginine- and ngouniensine-type skeletons and a non-natural variant within six to nine steps from tryptamine. The efficiency of our approach was demonstrated by successful total syntheses of (±)-vincadifformine, (±)-andranginine and (-)-catharanthine.

  17. The Rhazinilam-Leuconoxine-Mersicarpine Triad of Monoterpenoid Indole Alkaloids.

    PubMed

    Pfaffenbach, Magnus; Gaich, Tanja

    The rhazinilam-leuconoxine-mersicarpine triad of monoterpenoid indole alkaloids comprises a variety of diverse natural products with unprecedented structural features and intriguing biological activities. This subfamily of Aspidosperma alkaloids has drawn significant attention from the synthetic community which is reflected by over 20 syntheses within the last 5years. Numerous transformations and strategies have been developed to access the different key structural motifs such as the tetrahydroindolizine, α,β-unsaturated carbinolamide, diaza[5.5.6.6]fenestrane, and tetrahydro-2H-azepine frameworks. The present contribution comprehensively covers the abundant literature on this natural product class up to the end of May 2016, providing a detailed account of the formal and total syntheses which is complemented by an overview of their biosynthesis, spectroscopy, and pharmacology. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Studies on organic indole-3-aldehyde single crystals

    NASA Astrophysics Data System (ADS)

    Haja Hameed, A. S.; Ravi, G.; Dhanasekaran, R.; Ramasamy, P.

    Indole-3-aldehyde (IA) is a new organic nonlinear material for which its solubility in methanol and acetone was found out using the apparatus fabricated by the authors. In order to get the good-quality crystals, methods of evaporation of solvent at room temperature and slow cooling of saturated solution at boiling temperature were adopted. Simulated lattice parameter values were found out using experimentally known " d" values. The etching and mechanical strength studies on different planes of the crystal were carried out. Decomposition temperature, weight loss and different functional bond frequencies associated with the crystal were also found out from differential thermal analysis (DTA), thermo-gravimetric analysis (TGA) and Fourier transform infra-red (FTIR) spectroscopic analysis, respectively.

  19. Response of patients with indolent systemic mastocytosis to tamoxifen citrate.

    PubMed

    Butterfield, Joseph H; Chen, Dong

    2016-01-01

    We examined whether tamoxifen citrate at 20mg/day for 1 year had a beneficial effect on laboratory findings, bone marrow mastocytosis, common clinical symptoms, or quality-of-life assessment for 5 women and 2 men with indolent systemic mastocytosis. Tamoxifen was well tolerated. We found significant reductions in the platelet count, serum alkaline phosphatase, and 24-h urinary excretion of N-methylhistamine and significant increases in serum lactate dehydrogenase and (excluding 2 patients taking aspirin) in 24-h urinary excretion of 11β-prostaglandin F2α. Overall, no change occurred in percent involvement of bone marrow by mastocytosis. Symptom scores were mild and did not change during the treatment. The 36-Item Short Form Health Survey scores for quality of life physical and mental components showed no marked changes. Tamoxifen, an older, nonhematotoxic medication, has limited activity in systemic mastocytosis at the dosage used in this study.

  20. Kinetic mechanism of indole-3-glycerol phosphate synthase.

    PubMed

    Schlee, Sandra; Dietrich, Susanne; Kurćon, Tomasz; Delaney, Pamela; Goodey, Nina M; Sterner, Reinhard

    2013-01-08

    The (βα)(8)-barrel enzyme indole-3-glycerol phosphate synthase (IGPS) catalyzes the multistep transformation of 1-(o-carboxyphenylamino)-1-deoxyribulose 5-phosphate (CdRP) into indole-3-glycerol phosphate (IGP) in tryptophan biosynthesis. Mutagenesis data and crystal structure analysis of IGPS from Sulfolobus solfataricus (sIGPS) allowed for the formulation of a plausible chemical mechanism of the reaction, and molecular dynamics simulations suggested that flexibility of active site loops might be important for catalysis. Here we developed a method that uses extrinsic fluorophores attached to active site loops to connect the kinetic mechanism of sIGPS to structure and conformational motions. Specifically, we elucidated the kinetic mechanism of sIGPS and correlated individual steps in the mechanism to conformational motions of flexible loops. Pre-steady-state kinetic measurements of CdRP to IGP conversion monitoring changes in intrinsic tryptophan and IGP fluorescence provided a minimal three-step kinetic model in which fast substrate binding and chemical transformation are followed by slow product release. The role of sIGPS loop conformational motion during substrate binding and catalysis was examined via variants that were covalently labeled with fluorescent dyes at the N-terminal extension of the enzyme and mobile active site loop β1α1. Analysis of kinetic data monitoring dye fluorescence revealed a conformational change that follows substrate binding, suggesting an induced-fit-type binding mechanism for the substrate CdRP. Global fitting of all kinetic results obtained with wild-type sIGPS and the labeled variants was best accommodated by a four-step kinetic model. In this model, both the binding of CdRP and its on-enzyme conversion to IGP are accompanied by conformational transitions. The liberation of the product from the active site is the rate-limiting step of the overall reaction. Our results confirm the importance of flexible active loops for substrate