spiro compounds

Summary

Summary: A group of compounds consisting in part of two rings sharing one carbon atom in common.

Top Publications

  1. ncbi Spliceostatin A targets SF3b and inhibits both splicing and nuclear retention of pre-mRNA
    Daisuke Kaida
    Chemical Genetics Laboratory, RIKEN, 2 1 Hirosawa, Wako, Saitama 351 0198, Japan
    Nat Chem Biol 3:576-83. 2007
  2. pmc Reduced fidelity of branch point recognition and alternative splicing induced by the anti-tumor drug spliceostatin A
    Anna Corrionero
    Centre de Regulacio Genomica, 08003 Barcelona, Spain
    Genes Dev 25:445-59. 2011
  3. pmc Spliceostatin A inhibits spliceosome assembly subsequent to prespliceosome formation
    Gabriel A Roybal
    Department of Molecular, Cell and Developmental Biology and Center for Molecular Biology of RNA, University of California, Santa Cruz, CA, USA
    Nucleic Acids Res 38:6664-72. 2010
  4. pmc Effect of elatol, isolated from red seaweed Laurencia dendroidea, on Leishmania amazonensis
    Adriana Oliveira dos Santos
    Programa de Pós Graduação em Microbiologia, Universidade Estadual de Londrina, Rodovia Celso Garcia Cid, PR 445, Km 380, CEP 86051 990, Campus Universitario, Londrina, Parana, Brazil
    Mar Drugs 8:2733-43. 2010
  5. ncbi Chronic effects in mice caused by oral administration of sublethal doses of azaspiracid, a new marine toxin isolated from mussels
    Emiko Ito
    Research Center for Pathogenic Fungi and Microbial Toxicoses, Chiba University, 1 8 1 Inohana, Chuo Ku, Chiba 260 8673, Japan
    Toxicon 40:193-203. 2002
  6. pmc Optically switchable chelates: optical control and sensing of metal ions
    Tomoyo Sakata
    Department of Physiology, University of Wisconsin, 1300 University Avenue, Madison, Wisconsin 53706, USA
    J Org Chem 73:227-33. 2008
  7. ncbi A receptor in pituitary and hypothalamus that functions in growth hormone release
    A D Howard
    Merck Research Laboratories, Rahway, NJ 07065, USA
    Science 273:974-7. 1996
  8. ncbi Acute toxicity of pinnatoxins E, F and G to mice
    Rex Munday
    AgResearch Ltd, Ruakura Research Centre, Private Bag 3123, Hamilton, New Zealand
    Toxicon 60:995-9. 2012
  9. ncbi Marine algal pinnatoxins E and F cause neuromuscular block in an in vitro hemidiaphragm preparation
    Shane D Hellyer
    Department of Pharmacology and Toxicology, University of Otago School of Medical Sciences, Dunedin, New Zealand
    Toxicon 58:693-9. 2011
  10. ncbi Chemical defense of Mediterranean sponges Aplysina cavernicola and Aplysina aerophoba
    Carsten Thoms
    Institut fur Pharmazeutische Biologie, Universitat Dusseldorf, Universitatsstrasse 1, Geb 26 23, D 40225 Dusseldorf, Germany
    Z Naturforsch C 59:113-22. 2004

Research Grants

  1. TOTAL SYNTHESIS OF NATURAL PRODUCTS
    K Nicolaou; Fiscal Year: 2002
  2. TOTAL SYNTHESIS OF AZADIRACHTIN
    K Nicolaou; Fiscal Year: 2008
  3. Enabling Technologies for Combinatorial Chemistry
    K Nicolaou; Fiscal Year: 2005
  4. SYNTHESIS OF ANTICANCER AGENTS
    K C Nicolaou; Fiscal Year: 2010
  5. TOTAL SYNTHESIS OF APOPTOLIDIN
    K Nicolaou; Fiscal Year: 2004
  6. Synthesis of Macrolides, Steroids, Cyclopentanoids, etc.
    BARRY TROST; Fiscal Year: 2009
  7. Regulatory Role of Growth Hormone Secretagogue Receptor
    Roy Smith; Fiscal Year: 2007
  8. Design and Synthesis of HIV-1 Protease Inhibitors
    AMOS SMITH; Fiscal Year: 2004
  9. NMR systems : 2 Bruker Avance 500 Consoles
    AMOS SMITH; Fiscal Year: 2006
  10. SYNTHESIS OF CHLOROPEPTINS, GP120 CD4 BINDING INHIBITORS
    AMOS SMITH; Fiscal Year: 2001

Detail Information

Publications261 found, 100 shown here

  1. ncbi Spliceostatin A targets SF3b and inhibits both splicing and nuclear retention of pre-mRNA
    Daisuke Kaida
    Chemical Genetics Laboratory, RIKEN, 2 1 Hirosawa, Wako, Saitama 351 0198, Japan
    Nat Chem Biol 3:576-83. 2007
    ..Thus, the inhibition of pre-mRNA splicing during early steps involving SF3b allows unspliced mRNA leakage and translation...
  2. pmc Reduced fidelity of branch point recognition and alternative splicing induced by the anti-tumor drug spliceostatin A
    Anna Corrionero
    Centre de Regulacio Genomica, 08003 Barcelona, Spain
    Genes Dev 25:445-59. 2011
    ..Our results reveal a mechanism that prevents nonproductive base-pairing interactions in the spliceosome, and highlight the regulatory and cancer therapeutic potential of perturbing the fidelity of splice site recognition...
  3. pmc Spliceostatin A inhibits spliceosome assembly subsequent to prespliceosome formation
    Gabriel A Roybal
    Department of Molecular, Cell and Developmental Biology and Center for Molecular Biology of RNA, University of California, Santa Cruz, CA, USA
    Nucleic Acids Res 38:6664-72. 2010
    ..This work establishes SSA as a powerful tool for dissecting the dynamics of spliceosomes in cells. In addition our data will inform the design of synthetic splicing modulator compounds for targeted anti-tumor treatment...
  4. pmc Effect of elatol, isolated from red seaweed Laurencia dendroidea, on Leishmania amazonensis
    Adriana Oliveira dos Santos
    Programa de Pós Graduação em Microbiologia, Universidade Estadual de Londrina, Rodovia Celso Garcia Cid, PR 445, Km 380, CEP 86051 990, Campus Universitario, Londrina, Parana, Brazil
    Mar Drugs 8:2733-43. 2010
    ..Our studies indicated that elatol is a potent antiproliferative agent against promastigote and intracellular amastigote forms, and may have important advantages for the development of new anti-leishamanial chemotherapies...
  5. ncbi Chronic effects in mice caused by oral administration of sublethal doses of azaspiracid, a new marine toxin isolated from mussels
    Emiko Ito
    Research Center for Pathogenic Fungi and Microbial Toxicoses, Chiba University, 1 8 1 Inohana, Chuo Ku, Chiba 260 8673, Japan
    Toxicon 40:193-203. 2002
    ..Tumors were not observed in 11 mice treated at lower doses and in 19 control mice. Hyperplasia of epithelial cells was also observed in the stomach of six mice out of ten administered at 20 microg/kg...
  6. pmc Optically switchable chelates: optical control and sensing of metal ions
    Tomoyo Sakata
    Department of Physiology, University of Wisconsin, 1300 University Avenue, Madison, Wisconsin 53706, USA
    J Org Chem 73:227-33. 2008
    ..Fluorescence imaging of the MC state of nitroBIPS-8-TriA was used to quantify the rate and efficiency of optical switching and to provide a real-time readout of the state of the optically switchable chelate within living cells...
  7. ncbi A receptor in pituitary and hypothalamus that functions in growth hormone release
    A D Howard
    Merck Research Laboratories, Rahway, NJ 07065, USA
    Science 273:974-7. 1996
    ..On the basis of its pharmacological and molecular characterization, this GPC-R defines a neuroendocrine pathway for the control of pulsatile GH release and supports the notion that the GHSs mimic an undiscovered hormone...
  8. ncbi Acute toxicity of pinnatoxins E, F and G to mice
    Rex Munday
    AgResearch Ltd, Ruakura Research Centre, Private Bag 3123, Hamilton, New Zealand
    Toxicon 60:995-9. 2012
    ....
  9. ncbi Marine algal pinnatoxins E and F cause neuromuscular block in an in vitro hemidiaphragm preparation
    Shane D Hellyer
    Department of Pharmacology and Toxicology, University of Otago School of Medical Sciences, Dunedin, New Zealand
    Toxicon 58:693-9. 2011
    ..These results show that pinnatoxins E and F block neuromuscular transmission and suggest that observed in vivo muscle paralysis by pinnatoxin is due to selective antagonism of muscle type nicotinic acetylcholine receptors...
  10. ncbi Chemical defense of Mediterranean sponges Aplysina cavernicola and Aplysina aerophoba
    Carsten Thoms
    Institut fur Pharmazeutische Biologie, Universitat Dusseldorf, Universitatsstrasse 1, Geb 26 23, D 40225 Dusseldorf, Germany
    Z Naturforsch C 59:113-22. 2004
    ..sphinx and possibly also against other predators while the antibiotically active bioconversion products aeroplysinin-1 (5) and dienone (6) may protect sponges from invasion of bacterial pathogens...
  11. pmc MDM2 inhibitor MI-319 in combination with cisplatin is an effective treatment for pancreatic cancer independent of p53 function
    Asfar S Azmi
    Department of Pathology, Karmanos Cancer Institute, Wayne State University, School of Medicine, Detroit, MI, United States
    Eur J Cancer 46:1122-31. 2010
    ..In conclusion, this study highlights a new role of MDM2 inhibitors in combination with cisplatin, and thus warrants further clinical investigation in human pancreatic tumours containing both wt-p53 and mut-p53...
  12. ncbi Identification, characterization, and biological activity of specific receptors for natural (ghrelin) and synthetic growth hormone secretagogues and analogs in human breast carcinomas and cell lines
    P Cassoni
    Department of Biomedical Sciences and Oncology, University of Turin, 10126 Turin, Italy
    J Clin Endocrinol Metab 86:1738-45. 2001
    ..In conclusion, this study provides the first demonstration of specific GHS binding sites, other than GHS-R1, in breast cancer. These receptors probably mediate growth inhibitory effects on breast carcinoma cells in vitro...
  13. ncbi Spirotetrahydro beta-carbolines (spiroindolones): a new class of potent and orally efficacious compounds for the treatment of malaria
    Bryan K S Yeung
    Novartis Institute for Tropical Diseases, 10 Biopolis Road, No 05 01 Chromos, Singapore 138670
    J Med Chem 53:5155-64. 2010
    ..Improvement of the pharmacokinetic profile of the series translated to exceptional oral efficacy in the P. berghei infected malaria mouse model where full cure was achieved in four of five mice with three daily doses of 30 mg/kg...
  14. ncbi Isolation, structural determination and acute toxicity of pinnatoxins E, F and G
    Andrew I Selwood
    Cawthron Institute, Private Bag 2, Nelson, New Zealand
    J Agric Food Chem 58:6532-42. 2010
    ....
  15. pmc Meayamycin inhibits pre-messenger RNA splicing and exhibits picomolar activity against multidrug-resistant cells
    Brian J Albert
    Departments of 1Chemistry, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA
    Mol Cancer Ther 8:2308-18. 2009
    ..These data suggest that meayamycin is a useful chemical probe to study pre-mRNA splicing in live cells and is a promising lead as an anticancer agent...
  16. pmc Total synthesis of pinnatoxins A and G and revision of the mode of action of pinnatoxin A
    Romulo Araoz
    Institut de Neurobiologie Alfred Fessard, FRC2118, Laboratoire de Neurobiologie et Développement, UPR 3294, Centre National de la Recherche Scientifique, F 91198 Gif sur Yvette Cedex, France
    J Am Chem Soc 133:10499-511. 2011
    ....
  17. ncbi First direct fluorescence polarization assay for the detection and quantification of spirolides in mussel samples
    Paz Otero
    Departamento de Farmacologia, Facultad de Veterinaria, Universidad de Santiago de Compostela, Campus Universitario s n, 27002 Lugo, Spain
    Anal Chim Acta 701:200-8. 2011
    ..Other liposoluble toxins did not interfere with the assay, proving a specific method. Moreover, the matrix do not affect in the range of toxin concentrations that involving risk of spirolides intoxication...
  18. ncbi Pinnatoxins and spirolides in Norwegian blue mussels and seawater
    Thomas Rundberget
    Norwegian Veterinary Institute, Department of Laboratory Services, Oslo, Norway
    Toxicon 58:700-11. 2011
    ....
  19. ncbi In vitro and in vivo interaction of synthetic peroxide RBx11160 (OZ277) with piperaquine in Plasmodium models
    Christopher Snyder
    Swiss Tropical Institute, Socinstrasse 57, CH 4002 Basel, Switzerland
    Exp Parasitol 115:296-300. 2007
    ..1) was identified, suggesting that a RBx11160-piperaquine combination therapy in humans should allow each molecule to exert its full antimalarial effect...
  20. ncbi Identification of pinnatoxins and discovery of their fatty acid ester metabolites in mussels ( Mytilus edulis ) from eastern Canada
    Pearse McCarron
    Institute for Marine Biosciences, National Research Council Canada, 1411 Oxford Street, Halifax, Nova Scotia B3H 3Z1, Canada
    J Agric Food Chem 60:1437-46. 2012
    ..The occurrence of pinnatoxins in North American shellfish further highlights the international distribution of these toxins...
  21. ncbi Anti-tumour effects of elatol, a marine derivative compound obtained from red algae Laurencia microcladia
    Andreza Campos
    Department of Pharmacology Department of Pharmaceutical Sciences, Federal University of Santa Catarina, Florianopolis, SC, Brazil
    J Pharm Pharmacol 64:1146-54. 2012
    ..This paper aims to evaluate the anti-tumour properties of elatol, a compound (sesquiterpene) isolated from algae Laurencia microcladia...
  22. pmc Co-transcriptional degradation of aberrant pre-mRNA by Xrn2
    Lee Davidson
    Wellcome Trust Centre for Cell Biology, University of Edinburgh, Edinburgh, UK
    EMBO J 31:2566-78. 2012
    ..Our data therefore establish a previously unknown function for Xrn2 and an important further aspect of pre-mRNA metabolism that occurs co-transcriptionally...
  23. pmc Probing the antimalarial mechanism of artemisinin and OZ277 (arterolane) with nonperoxidic isosteres and nitroxyl radicals
    Matthias A Fügi
    Swiss Tropical Institute, Socinstrasse 57, CH 4002 Basel, Switzerland
    Antimicrob Agents Chemother 54:1042-6. 2010
    ..The latter had no effect on the antimalarial activities of the former. These data indicate that the antimalarial properties of peroxides do not derive from reversible interactions with parasite targets...
  24. pmc Structural determinants in phycotoxins and AChBP conferring high affinity binding and nicotinic AChR antagonism
    Yves Bourne
    Architecture et Fonction des Macromolecules Biologiques, Centre National de la Recherche Scientifique, Universite d Aix Marseille, Campus Luminy Case 932, F 13288 Marseille Cedex 9, France
    Proc Natl Acad Sci U S A 107:6076-81. 2010
    ....
  25. pmc Reactivation of p53 by novel MDM2 inhibitors: implications for pancreatic cancer therapy
    Asfar S Azmi
    Department of Pathology, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI 48201, USA
    Curr Cancer Drug Targets 10:319-31. 2010
    ..No tumor inhibition was found in mut-p53 BxPC-3 xenografts. In light of our results, the inhibitors of MDM2 warrant clinical investigation as new agents for PC treatment...
  26. ncbi In vitro anti-trypanosomal activity of elatol isolated from red seaweed Laurencia dendroidea
    P Veiga-Santos
    Programa de Pós Graduação em Ciências Farmacêuticas, Laboratório de Inovação Tecnológica no Desenvolvimento de Fármacos e Cosméticos, Bloco B 08, Universidade Estadual de Maringa, Av Colombo 5790, CEP 87020 900 Maringa, Parana, Brazil
    Parasitology 137:1661-70. 2010
    ..This is the first report of the anti-trypanosomal effect of the sesquiterpene elatol...
  27. ncbi MDM2 inhibitors for cancer therapy
    Lyubomir T Vassilev
    Discovery Oncology, Roche Research Center, Hoffmann La Roche Inc, Nutley, NJ 07110, USA
    Trends Mol Med 13:23-31. 2007
    ..Here, the new developments in the quest for pharmacological p53 activators are reviewed with an emphasis on small-molecule inhibitors of the p53-MDM2 interaction...
  28. pmc Benzothiazinones kill Mycobacterium tuberculosis by blocking arabinan synthesis
    Vadim Makarov
    A N Bakh Institute of Biochemistry, Russian Academy of Science, 119071 Moscow, Russia
    Science 324:801-4. 2009
    ..The most advanced compound, BTZ043, is a candidate for inclusion in combination therapies for both drug-sensitive and extensively drug-resistant TB...
  29. pmc The catalytic asymmetric total synthesis of elatol
    David E White
    Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, California 91125, USA
    J Am Chem Soc 130:810-1. 2008
    ..This strategy represents a general platform for accessing the chamigrene natural product family, as demonstrated by the synthesis of (+)-laurencenone B as an intermediate in our route...
  30. pmc Temporal activation of p53 by a specific MDM2 inhibitor is selectively toxic to tumors and leads to complete tumor growth inhibition
    Sanjeev Shangary
    Comprehensive Cancer Center and Department of Internal Medicine, University of Michigan, 1500 East Medical Center Drive, Ann Arbor, MI 48109, USA
    Proc Natl Acad Sci U S A 105:3933-8. 2008
    ..MI-219 activates p53 in normal tissues with minimal p53 accumulation and is not toxic to animals. MI-219 warrants clinical investigation as a new agent for cancer treatment...
  31. ncbi Sanglifehrin a blocks key dendritic cell functions in vivo and promotes long-term allograft survival together with low-dose CsA
    H Hackstein
    Institute for Clinical Immunology and Transfusion Medicine, Justus Liebig University, Giessen, Germany
    Am J Transplant 7:789-98. 2007
    ..We propose that SFA represents a novel class of immunophilin-binding immunosuppressants with high activity against DCs and the development of graft vasculopathy in CsA-treated recipients...
  32. ncbi First evidence of spirolides in Spanish shellfish
    A Villar González
    EU Community Reference Laboratory on Marine Biotoxins, Agencia Española Seguridad Alimentaria, Estación Marítima s n 36200 Vigo, Spain
    Toxicon 48:1068-74. 2006
    ..The combination of different MS modes of operation, just as enhanced MS (EMS) and MS(3) experiments, allowed to confirm the first occurrence of spirolides in Spanish shellfish...
  33. ncbi New protocol to obtain spirolides from Alexandrium ostenfeldii cultures with high recovery and purity
    Paz Otero
    Departamento de Farmacologia, Facultad de Veterinaria, Universidad de Santiago de Compostela, 27002 Lugo, Spain
    Biomed Chromatogr 24:878-86. 2010
    ..The protocol proposed shows, for the first time, a complete and detailed methodology to separate and purify spirolide toxins with high purity, recovery, repeatability and stability...
  34. ncbi Biosynthesis of 13-desmethyl spirolide C by the dinoflagellate Alexandrium ostenfeldii
    Shawna L MacKinnon
    Institute for Marine Biosciences, National Research Council of Canada, 1411 Oxford Street, Halifax NS, Canada B3H 3Z1
    J Org Chem 71:8724-31. 2006
    ..This work represents the first conclusive evidence that such cyclic imine toxins are polyketides and provides support for biosynthetic pathways previously defined for other polyether dinoflagellate toxins...
  35. ncbi Vincristine induces dramatic lysosomal changes and sensitizes cancer cells to lysosome-destabilizing siramesine
    Line Groth-Pedersen
    Apoptosis Department and Centre for Genotoxic Stress Research, Institute of Cancer Biology, Danish Cancer Society, Strandboulevarden 49, DK 2100 Copenhagen, Denmark
    Cancer Res 67:2217-25. 2007
    ..These data strongly suggest that combination therapies consisting of microtubule-disturbing and lysosome-destabilizing drugs may prove useful in the treatment of otherwise therapy-resistant human cancers...
  36. ncbi First identification of azaspiracid and spirolides in Mesodesma donacium and Mulinia edulis from Northern Chile
    Gonzalo Alvarez
    Centro de Investigacións Mariñas Xunta de Galicia, Apto 13, 36620 Vilanova de Arousa, Pontevedra, Spain
    Toxicon 55:638-41. 2010
    ..This is the first report of the occurrence of these groups of toxins in Chile and suggests that it is necessary to monitor routinely these substances to warrant public health and shellfish exportations...
  37. ncbi The cephalostatin way of apoptosis
    Anita Rudy
    Department of Pharmacy, University of Munich, Munich, Germany
    J Nat Prod 71:482-6. 2008
    ..Cephalostatin 1 ( 1), therefore, provides a very good tool to discover novel apoptotic pathways, which might be important in the understanding and treatment of chemo-resistant cancer...
  38. ncbi Synthesis and anticancer activity of side chain analogs of the crambescidin alkaloids
    Zachary D Aron
    Department of Chemistry, 516 Rowland Hall, University of California, Irvine, CA 92697 2025, USA
    Bioorg Med Chem Lett 14:3445-9. 2004
    ..In addition, substantial variations in tumor selectivity with structure were seen. Crambescidin analogs having short, nonpolar side chains were identified for the first time as promising anticancer agents...
  39. ncbi Geographical, temporal, and species variation of the polyether toxins, azaspiracids, in shellfish
    Ambrose Furey
    PROTEOBIO, Mass Spectrometry Center for Proteomics and Biotoxin Research, Department of Chemistry, Cork Institute of Technology, Bishopstown, Cork, Ireland
    Environ Sci Technol 37:3078-84. 2003
    ..Although human intoxications have so far only been associated with mussel consumption, the discovery of significant azaspiracid accumulation in other bivalve mollusks could pose a threat to human health...
  40. ncbi The hydantoin lesions formed from oxidation of 7,8-dihydro-8-oxoguanine are potent sources of replication errors in vivo
    Paul T Henderson
    Biological Engineering Division and Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
    Biochemistry 42:9257-62. 2003
    ..Were these lesions to be formed in vivo, our data show that they are absolutely miscoding and may be refractory to repair after translesion synthesis...
  41. ncbi The first identification of azaspiracids in shellfish from France and Spain
    Ana Braña Magdalena
    PROTEOBIO, Mass Spectrometry Centre for Proteomics and Biotoxin Research, Department of Chemistry, Cork Institute of Technology, Bishopstown, Cork, Ireland
    Toxicon 42:105-8. 2003
    ..24 microg/g, from Galicia, Spain, and scallops (Pecten maximus), 0.32 microg/g, from Brittany, France. Toxin profiles were similar to those found in the equivalent shellfish in Ireland in which AZA1 was the predominant toxin...
  42. ncbi Dinuclear zinc catalyzed asymmetric spirannulation reaction: an umpolung strategy for formation of α-alkylated-α-hydroxyoxindoles
    Barry M Trost
    Department of Chemistry, Stanford University, Stanford, California 94305 5080, United States
    Org Lett 14:2446-9. 2012
    ..The stereoselective Michael additions of 3-hydroxyoxindoles and the subsequent transesterifications afford spirocyclic δ-lactones. ..
  43. ncbi Azaspiracid shellfish poisoning: unusual toxin dynamics in shellfish and the increased risk of acute human intoxications
    K J James
    Ecotoxicology Research Unit, Chemistry Department, Cork Institute of Technology, Bishopstown, Cork, Ireland
    Food Addit Contam 19:555-61. 2002
    ..It was also observed that the toxin profiles differed significantly in various mussel tissues with AZA1 as the predominant toxin in the digestive glands and AZA3 predominant in the remaining tissues...
  44. ncbi Strategies for the enantioselective synthesis of spirooxindoles
    Nicolas R Ball-Jones
    Department of Chemistry, University of California, One Shields Avenue, Davis, California 95616, USA
    Org Biomol Chem 10:5165-81. 2012
    ..Strategies are also compared for the synthesis of non-spirocyclic 3,3'-disubstituted oxindoles...
  45. ncbi Synthesis of and a comparative study on the inhibition of muscle and liver glycogen phosphorylases by epimeric pairs of d-gluco- and d-xylopyranosylidene-spiro-(thio)hydantoins and N-(d-glucopyranosyl) amides
    L Somsak
    Department of Organic Chemistry, University of Debrecen, POB 20, H 4010 Debrecen, Hungary
    J Med Chem 44:2843-8. 2001
    ..The study of epimeric pairs of D-gluco and D-xylo configurated spiro-hydantoins and N-(D-glucopyranosyl)amides corroborated the role of specific hydrogen bridges in binding the inhibitors to the enzyme...
  46. ncbi Facile synthesis of dispirooxindole-fused heterocycles via domino 1,4-dipolar addition and Diels-Alder reaction of in situ generated Huisgen 1,4-dipoles
    Jing Sun
    College of Chemistry and Chemical Engineering, Yangzhou University, Yangzhou 225002, China
    Org Lett 14:5172-5. 2012
    ..The key strategies involve a domino 1,4-dipolar addition and Diels-Alder reaction of the in situ generated Huisgen 1,4-dipoles from the addition reaction of 4-dimethylaminopyridine with acetylenedicarboxylate to 3-phenacylideneoxindole...
  47. ncbi Mast cell apoptosis induced by siramesine, a sigma-2 receptor agonist
    Jane Spirkoski
    Swedish University of Agricultural Sciences, Dept of Anatomy, Physiology and Biochemistry, BMC Box 575, 75123, Uppsala, Sweden
    Biochem Pharmacol 84:1671-80. 2012
    ..The present study shows for the first time that MCs are highly sensitive to apoptosis induced by siramesine and introduces the possibility of using siramesine as a therapeutic agent for treatment of MC-dependent disease...
  48. pmc Rational design, synthesis, and characterization of highly fluorescent optical switches for high-contrast optical lock-in detection (OLID) imaging microscopy in living cells
    Chutima Petchprayoon
    Department of Bioengineering, University of California, Berkeley, CA 94720, USA
    Bioorg Med Chem 19:1030-40. 2011
    ..High fidelity optical switching of TMR fluorescence is shown for TMR-NISO probes in vitro and for membrane permeable TMR-NISO within living cells...
  49. pmc Stability of cyclic imine toxins: interconversion of pinnatoxin amino ketone and pinnatoxin A in aqueous media
    Jeffrey J Jackson
    Department of Chemistry and Biochemistry, University of California, Santa Barbara, California 93106 9510, USA
    J Org Chem 77:10435-40. 2012
    ..These studies, as well the access to PnTX amino ketone, were enabled by the total synthesis of (+)-pinnatoxin A completed previously in our laboratory...
  50. ncbi Facile synthesis of spiro[indoline-3,3'-pyrrolo[1,2-a]quinolines] and spiro[indoline-3,1'-pyrrolo[2,1-a]isoquinolines] via 1,3-dipolar cycloaddition reactions of heteroaromatic ammonium salts with 3-phenacylideneoxindoles
    Lei Wu
    College of Chemistry and Chemical Engineering, Yangzhou University, Yangzhou 225002, China
    Org Biomol Chem 10:9452-63. 2012
    ..The characterization data of spiro compounds and single crystal determination indicated that this 1,3-cycloaddition reaction is a regioselective and ..
  51. ncbi Anti-inflammatory effect of the spirocyclopiperazinium compound LXM-10 in mice and rats
    Yulan Xiong
    State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing, 100191, PR China
    Eur J Pharmacol 626:290-6. 2010
    ..Median lethal dose (LD(50)) of LXM-10 was 1573.0 micromol/kg. Our findings suggest that LXM-10 has anti-inflammatory effects by activating alpha7 nicotinic and M(4) muscarinic acetylcholine receptors with limited side effects...
  52. ncbi Antinociceptive mechanism of the spirocyclopiperazinium compound LXM-10 in mice and rats
    Yulan Xiong
    State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing 100191, PR China
    Pharmacol Biochem Behav 95:192-7. 2010
    ....
  53. ncbi Human muscarinic acetylcholine receptors are a target of the marine toxin 13-desmethyl C spirolide
    Carolina B Wandscheer
    Departamento de Farmacología, Facultad de Veterinaria, Universidad de Santiago de Compostela, Campus Universitario, Lugo, Spain
    Chem Res Toxicol 23:1753-61. 2010
    ..The 13-desmethyl C spirolide targets mAChRs causing a reduction of function, a decrease of specific antagonist binding to mAChRs, and alteration of membrane-bound receptors that might have important toxicological implications...
  54. pmc Quantitation of four guanine oxidation products from reaction of DNA with varying doses of peroxynitrite
    Hongbin Yu
    Biological Engineering Division, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Room 56 731A, Cambridge, Massachusetts 02139, USA
    Chem Res Toxicol 18:1849-57. 2005
    ..The complexity of these dose-response relationships is likely due to the dual role of peroxynitrite as both an oxidant and a nucleophile in competition with water...
  55. ncbi Spiroiminodihydantoin is the major product of the 8-oxo-7,8-dihydroguanosine reaction with peroxynitrite in the presence of thiols and guanosine photooxidation by methylene blue
    J C Niles
    Division of Bioengineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Room 56-731A, Cambridge, Massachusetts 02139, USA
    Org Lett 3:963-6. 2001
    ..Additionally, we have found that the spiroiminodihydantoin, and not the previously reported 4-hydroxy-8-oxo-4,8-dihydroguanosine, is the major final product formed during the methylene blue-mediated photooxidation of guanosine...
  56. ncbi Improved isolation procedure for azaspiracids from shellfish, structural elucidation of azaspiracid-6, and stability studies
    Jane Kilcoyne
    Marine Institute, Renville, Oranmore, County Galway, Ireland
    J Agric Food Chem 60:2447-55. 2012
    ..The stability of 6 relative to 1 was also assessed in three solvents in a short-term study that demonstrated the greatest stability in aqueous acetonitrile...
  57. ncbi Spiro and dispiro-1,2,4-trioxolanes as antimalarial peroxides: charting a workable structure-activity relationship using simple prototypes
    Yuxiang Dong
    College of Pharmacy, University of Nebraska Medical Center, 986025 Nebraska Medical Center, Omaha, Nebraska 68198 6025, USA
    J Med Chem 48:4953-61. 2005
    ..In pharmacokinetic experiments, four trioxolanes had high plasma clearance values, suggesting a potential metabolic instability. The toxicological profiles of two trioxolanes were comparable to that of artesunate...
  58. ncbi The preparation of certified calibration solutions for azaspiracid-1, -2, and -3, potent marine biotoxins found in shellfish
    Ruth A Perez
    National Research Council of Canada, Institute for Marine Biosciences, 1411 Oxford Street, Halifax, Nova Scotia B3H 3Z1, Canada
    Anal Bioanal Chem 398:2243-52. 2010
    ..The calibration solutions are suitable for method development, method validation, calibration of liquid chromatography or mass spectrometry instrumentation and quality control of shellfish monitoring programs...
  59. ncbi Discovery of XEN907, a spirooxindole blocker of NaV1.7 for the treatment of pain
    Sultan Chowdhury
    Department of Medicinal Chemistry, Xenon Pharmaceuticals Inc, Burnaby, British Columbia, Canada
    Bioorg Med Chem Lett 21:3676-81. 2011
    ..7 blocker. This lead compound, which in turn showed a further 10-fold increase in potency, represents a promising structure for further optimization efforts...
  60. ncbi LC-MS-MS aboard ship: tandem mass spectrometry in the search for phycotoxins and novel toxigenic plankton from the North Sea
    Bernd Krock
    Alfred Wegener Institut fur Polar und Meeresforschung, Am Handelshafen 12, 27570, Bremerhaven, Germany
    Anal Bioanal Chem 392:797-803. 2008
    ..On-board LC-MS-MS is a valuable method for near real-time analysis of phycotoxins in plankton for studies on bloom dynamics and the fate of toxins in the food web, and for characterization and isolation of putatively toxigenic organisms...
  61. ncbi Spiroiminodihydantoin and guanidinohydantoin are the dominant products of 8-oxoguanosine oxidation at low fluxes of peroxynitrite: mechanistic studies with 18O
    Jacquin C Niles
    Biological Engineering Division and Department of Chemistry, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Room 56 738A, Cambridge, Massachusetts 02139, USA
    Chem Res Toxicol 17:1510-9. 2004
    ..To explain the pH-dependent Gh and Sp yields, we propose that 5 has a pKa approximately 5.8 and that the differential reactivity of the protonated and deprotonated form of 5 leads to its partitioning into Gh and Sp, respectively...
  62. ncbi A unique approach to the concise synthesis of highly optically active spirooxazolines and the discovery of a more potent oxindole-type phytoalexin analogue
    Xianxing Jiang
    Key Laboratory of Preclinical Study for New Drugs of Gansu Province, Institute of Biochemistry and Molecular Biology, Lanzhou University, Lanzhou, China
    J Am Chem Soc 132:15328-33. 2010
    ..Preliminary biological evaluation of several of the spirooxazolines using a model of acute neuroinflammation revealed promising antipyretic activity and provided an opportunity to discover new antipyretic agents...
  63. ncbi Characterization of a Dispiroketal Spirolide Subclass from Alexandrium ostenfeldii
    Joy S Roach
    Institute for Marine Biosciences, National Research Council of Canada, Halifax, Nova Scotia, Canada B3H 3Z1
    J Nat Prod 72:1237-40. 2009
    ..Spirolide H contains this cyclic imine moiety but does not show toxicity in the mouse assay, suggesting that the presence of the cyclic imine moiety is not the only structural requirement for toxicity...
  64. ncbi Preparation and synthetic applications of 2-halotryptophan methyl esters: synthesis of spirotryprostatin B
    Fumiko Y Miyake
    Department of Chemistry, Oregon State University, Corvallis, OR 97331, USA
    Angew Chem Int Ed Engl 43:5357-60. 2004
  65. ncbi Identification of a novel spiropiperidine opioid receptor-like 1 antagonist class by a focused library approach featuring 3D-pharmacophore similarity
    Yasuhiro Goto
    Banyu Tsukuba Research Institute, Banyu Pharmaceutical Co Ltd, Okubo 3, Tsukuba 300 2611, Japan
    J Med Chem 49:847-9. 2006
    ..A novel D-proline amide class was identified in this library and was found to possess potent ORL1 antagonistic activity...
  66. ncbi Organocatalytic synthesis of spiro[pyrrolidin-3,3'-oxindoles] with high enantiopurity and structural diversity
    Xiao Hua Chen
    Hefei National Laboratory for Physical Sciences at the Microscale and Department of Chemistry, University of Science and Technology of China, Hefei, 230026, China
    J Am Chem Soc 131:13819-25. 2009
    ....
  67. ncbi Novel, one-pot, three-component route to indol-3-yl substituted spirooxindole derivatives
    Tao Chen
    Key Laboratory of Organic Synthesis of Jiangsu Province, College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou 215123, China
    J Comb Chem 12:659-63. 2010
    ....
  68. ncbi Structure-activity studies on the nociceptin/orphanin FQ receptor antagonist 1-benzyl-N-{3-[spiroisobenzofuran-1(3H),4'-piperidin-1-yl]propyl} pyrrolidine-2-carboxamide
    Claudio Trapella
    Department of Pharmaceutical Sciences and Biotechnology Center, University of Ferrara, via Fossato di Mortara 19, 44100 Ferrara, Italy
    Bioorg Med Chem 17:5080-95. 2009
    ..However compound 35 was found inactive when challenged against N/OFQ in vivo in the mouse tail withdrawal assay. Thus, the usefulness of the novel NOP ligand compound 35 is limited to in vitro investigations...
  69. ncbi Evaluation of various pH and temperature conditions on the stability of azaspiracids and their importance in preparative isolation and toxicological studies
    Carmen Alfonso
    Departamento de Farmacologia, Facultad de Veterinaria, Universidad de Santiago de Compostela, 27002 Lugo, Spain
    Anal Chem 80:9672-80. 2008
    ..Finally, the toxic potential of acid degradation products of AZAs was found to be dramatically reduced compared to the parent compounds, as assessed through cytotoxicity...
  70. ncbi Quantitative analysis of azaspiracids in Azadinium spinosum cultures
    Thierry Jauffrais
    IFREMER, Laboratoire EMP PHYC, Rue de l Ile d Yeu, 44311, Nantes, France
    Anal Bioanal Chem 403:833-46. 2012
    ..5 × 10(9) μm(3). Moreover, experiments carried out to clarify the formation and structure of methylated AZA analogues led to the description of two AZA methyl esters and to the correction of the chemical structures of AZAs29-32...
  71. ncbi Lihouidine, a novel spiro polycyclic aromatic alkaloid from the marine sponge Suberea n. sp. (Aplysinellidae, Verongida)
    Bruce F Bowden
    Department of Chemistry, School of Pharmacy and Molecular Sciences, James Cook University, Townsville, Qld 4811, Australia
    J Org Chem 69:7791-3. 2004
    ..The structure of the alkaloid, which was racemic, was determined by a combination of 1D and 2D NMR techniques and single-crystal X-ray structural analysis...
  72. ncbi Structure of human cyclophilin A in complex with the novel immunosuppressant sanglifehrin A at 1.6 A resolution
    Joerg Kallen
    Protein Structure Unit, Novartis Institutes for BioMedical Research, CH 4002 Basel, Switzerland
    J Biol Chem 280:21965-71. 2005
    ..This observation raises the possibility that the dimer of CypA.SFA complexes is the molecular species mediating the immunosuppressive effect...
  73. ncbi Cutting edge: sanglifehrin A, a novel cyclophilin-binding immunosuppressant blocks bioactive IL-12 production by human dendritic cells
    Christoph Steinschulte
    Institute for Clinical Immunology and Transfusion Medicine, Justus Liebig University, Giessen, Germany
    J Immunol 171:542-6. 2003
    ..Real-time RT-PCR reveals 84-94% suppression of IL-12p40, IL-12p35, and IL-23-specific p19 transcription. These novel insights into the immunosuppressive action of SFA are likely to impact on the clinical use of this agent...
  74. ncbi The novel cyclophilin binding compound, sanglifehrin A, disassociates G1 cell cycle arrest from tolerance induction
    Amy Allen
    Division of Immunology and Hematopoeisis, Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA
    J Immunol 172:4797-803. 2004
    ..Based on these data, we propose that the decision as to whether TCR engagement will lead to productive activation or tolerance is dictated by a rapamycin -inhibitable pathway, independent of the G(1)-->S phase cell cycle progression...
  75. ncbi Anti-cancer agent siramesine is a lysosomotropic detergent that induces cytoprotective autophagosome accumulation
    Marie Stampe Ostenfeld
    Apoptosis Department and Centre for Genotoxic Stress Response, Institute for Cancer Biology, Danish Cancer Society, Copenhagen, Denmark
    Autophagy 4:487-99. 2008
    ..Threrefore, the combination of siramesine with inhibitors of autophagosome formation appears as a promising approach for future cancer therapy...
  76. ncbi Identification of an antimalarial synthetic trioxolane drug development candidate
    Jonathan L Vennerstrom
    College of Pharmacy, University of Nebraska Medical Center, 986025 Nebraska Medical Center, Omaha, Nebraska 68198 6025, USA
    Nature 430:900-4. 2004
    ..Here we describe how a synthetic peroxide antimalarial drug development candidate was identified in a collaborative drug discovery project...
  77. ncbi Pseudoceratins A and B, antifungal bicyclic bromotyrosine-derived metabolites from the marine sponge Pseudoceratina purpurea
    Jae Hyuk Jang
    Laboratory of Aquatic Natural Products Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Bunkyo ku, Tokyo 113 8657, Japan
    J Org Chem 72:1211-7. 2007
    ..Pseudoceratins exhibited significant antifungal activity against Candida albicans...
  78. pmc MI-63: a novel small-molecule inhibitor targets MDM2 and induces apoptosis in embryonal and alveolar rhabdomyosarcoma cells with wild-type p53
    J A Canner
    Department of Pediatrics, Nationwide Children s Hospital, Columbus, OH, USA
    Br J Cancer 101:774-81. 2009
    ....
  79. ncbi Recognition of privileged structures by G-protein coupled receptors
    Kent Bondensgaard
    Protein Engineering, Medicinal Chemistry, and Discovery Biology, Novo Nordisk A S, Novo Nordisk Park, DK 2760 Måløv, Denmark
    J Med Chem 47:888-99. 2004
    ....
  80. pmc Exploring the links between natural products and bacterial assemblages in the sponge Aplysina aerophoba
    Oriol Sacristán-Soriano
    Centro de Estudios Avanzados de Blanes CSIC, Accés a la Cala St Francesc 14, 17300 Blanes, Girona, Spain
    Appl Environ Microbiol 77:862-70. 2011
    ..Further investigating these associations will shed light on the organization and functioning of host-endobiont systems such as Aplysina aerophoba...
  81. pmc An MDM2 antagonist (MI-319) restores p53 functions and increases the life span of orally treated follicular lymphoma bearing animals
    Ramzi M Mohammad
    Division of Hematology and Oncology, Department of Internal Medicine, Karmanos Cancer Institute, Wayne State University School of Medicine, 732 HWCRC, 4100 John R Street, Detroit, Michigan 48201, USA
    Mol Cancer 8:115. 2009
    ..For comparison purpose, MI-319, MI-219 and Nutlin-3 were assessed side by side against FSCCL and three other B-cell hematological tumor cell lines in growth inhibition and gene expression profiling experiments...
  82. ncbi New paralytic alkaloids, asperparalines A, B and C, from Aspergillus japonicus JV-23
    H Hayashi
    Department of Applied Biological Chemistry, College of Agriculture, Osaka Prefecture University, Japan
    Biosci Biotechnol Biochem 64:111-5. 2000
    ..Their structures were elucidated by spectroscopic methods and X-ray crystallography. These asperparalines showed paralytic activity against silk worms...
  83. ncbi First report on azaspiracid and yessotoxin groups detection in French shellfish
    Zouher Amzil
    IFREMER, Microbiology and Phycotoxins Department, BP 21105, 44311 Nantes, France
    Toxicon 52:39-48. 2008
    ..This paper reports for the first time on AZA and YTX-groups detection in French shellfish...
  84. ncbi Structure-based design of spiro-oxindoles as potent, specific small-molecule inhibitors of the MDM2-p53 interaction
    Ke Ding
    Department of Internal Medicine, Comprehensive Cancer Center, Life Sciences Institute, University of Michigan, 1500 E Medical Center Drive, Ann Arbor, 48109, USA
    J Med Chem 49:3432-5. 2006
    ..MI-63 has excellent specificity over cancer cells with deleted p53 and shows a minimal toxicity to normal cells...
  85. ncbi Effective tumor cell death by sigma-2 receptor ligand siramesine involves lysosomal leakage and oxidative stress
    Marie Stampe Ostenfeld
    Apoptosis Department, Institute for Cancer Biology, Danish Cancer Society, Copenhagen, Denmark
    Cancer Res 65:8975-83. 2005
    ..c. fibrosarcoma models in mice. These results present siramesine as a promising new drug for the treatment of tumors resistant to traditional therapies...
  86. ncbi The novel cyclophilin-binding drug sanglifehrin A specifically affects antigen uptake receptor expression and endocytic capacity of human dendritic cells
    Andrea M Woltman
    Department of Nephrology, Leiden University Medical Center, Leiden, The Netherlands
    J Immunol 172:6482-9. 2004
    ..In contrast, FcalphaRI (CD89) and FcgammaRII (CD32) were increased by SFA. The explicit effect of SFA on the expression of Ag uptake receptors and Ag capture by DCs makes SFA unique among immunophilin-binding immunosuppressive drugs...
  87. ncbi Cyclophilin sensitivity to sanglifehrin A can be correlated to the same specific tryptophan residue as cyclosporin A
    Trevor J Pemberton
    The School of Life Sciences, University of Sussex and The Brighton and Sussex Medical School, Falmer, Brighton East Sussex BN1 9QG, UK
    FEBS Lett 555:335-40. 2003
    ....
  88. ncbi Discovery of new analogs of the marine biotoxin azaspiracid in blue mussels (Mytilus edulis) by ultra-performance liquid chromatography/tandem mass spectrometry
    Nils Rehmann
    Marine Institute, Rinville, Oranmore, Co Galway, Ireland
    Rapid Commun Mass Spectrom 22:549-58. 2008
    ..All the new AZA analogs were present at low concentrations in the shellfish and it is probably safe to assume that they do not pose a risk for the shellfish consumer...
  89. ncbi Paraherquamides, brevianamides, and asperparalines: laboratory synthesis and biosynthesis. An interim report
    Robert M Williams
    Department of Chemistry, Colorado State University, Fort Collins, Colorado 80523, USA
    Acc Chem Res 36:127-39. 2003
    ..Key biosynthetic studies are described, along with classical synthetic approaches as well as those inspired by Nature for the synthesis of these interesting molecules...
  90. ncbi The total synthesis of spirotenuipesines A and B
    Mingji Dai
    Department of Chemistry, Columbia University, Havemeyer Hall, 3000 Broadway, New York, New York 10027, USA
    J Am Chem Soc 129:3498-9. 2007
  91. ncbi Detection of five new hydroxyl analogues of azaspiracids in shellfish using multiple tandem mass spectrometry
    Kevin J James
    PROTEOBIO, Department of Chemistry, Mass Spectrometry Centre for Proteomics and Biotoxin Research, Cork Institute of Technology, Bishopstown, Cork, Ireland
    Toxicon 41:277-83. 2003
    ....
  92. ncbi Aldose reductase inhibition by AS-3201 in sural nerve from patients with diabetic sensorimotor polyneuropathy
    Vera Bril
    Department of Medicine, University of Toronto, Ontario, Canada
    Diabetes Care 27:2369-75. 2004
    ..An additional aim was to determine whether any changes in nerve function would manifest with AS-3201 therapy...
  93. ncbi Effects of Azaspiracids 2 and 3 on intracellular cAMP, [Ca2+], and pH
    Yolanda Roman
    Departamentos de Farmacología and Departamento de Fisiología, Facultad de Veterinaria, Universidad de Santiago de Compostela, 27002 Lugo, Spain
    Chem Res Toxicol 17:1338-49. 2004
    ..Thus, both analogues seem to involve an AC pathway, although its effects on [Ca(2+)](i) and pH(i) are quite different...
  94. ncbi Freeze-drying for the stabilisation of shellfish toxins in mussel tissue (Mytilus edulis) reference materials
    Pearse McCarron
    Marine Institute, Marine Environment and Food Safety Service, Rinville, Oranmore, Galway, Ireland
    Anal Bioanal Chem 387:2475-86. 2007
    ..Figure Aliquots of freeze-dried and wet mussel tissue reference materials containing the various shellfish toxins examined in the study...
  95. ncbi Irreversible cytoskeletal disarrangement is independent of caspase activation during in vitro azaspiracid toxicity in human neuroblastoma cells
    Natalia Vilariño
    Departamento de Farmacologia, Facultad de Veterinaria, Universidad de Santiago de Compostela, Campus Universitario, 27002 Lugo, Spain
    Biochem Pharmacol 74:327-35. 2007
    ....
  96. ncbi Total synthesis of the proposed azaspiracid-1 structure, part 1: construction of the enantiomerically pure C1-C20, C21-C27, and C28-C40 fragments
    K C Nicolaou
    Department of Chemistry, The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
    Angew Chem Int Ed Engl 42:3643-8. 2003
  97. ncbi Lu 28-179 labels a sigma(2)-site in rat and human brain
    Karina Krøyer Søby
    Department of Molecular Pharmacology, H Lundbeck A S, Biological Research, DK 2500, Valby, Denmark
    Neuropharmacology 43:95-100. 2002
    ..Overall, these data are consistent with [(3)H]Lu 28-179 labelling a sigma(2)-like binding site...
  98. ncbi Sanglifehrin A, a novel cyclophilin-binding compound showing immunosuppressive activity with a new mechanism of action
    G Zenke
    Transplantation Research, Core Technology, and Nervous System Research, Novartis Pharma, Basel, Switzerland
    J Immunol 166:7165-71. 2001
    ..In summary, we have identified a novel immunosuppressant, which represents, in addition to CsA, FK506 and rapamycin, a fourth class of immunophilin-binding metabolites with a new, yet undefined mechanism of action...
  99. ncbi Structures of azaspiracid analogs, azaspiracid-4 and azaspiracid-5, causative toxins of azaspiracid poisoning in Europe
    K Ofuji
    Graduate School of Agricultural Science, Tohoku University, Sendai, Japan
    Biosci Biotechnol Biochem 65:740-2. 2001
    ....
  100. ncbi Binding of 125I-labeled ghrelin to membranes from human hypothalamus and pituitary gland
    G Muccioli
    Department of Anatomy, Pharmacology and Forensic Medicine, University of Turin, Italy
    J Endocrinol Invest 24:RC7-9. 2001
    ..These receptors are the specific binding sites for GHS and their antagonists, as well as for SRIH analogs (vapreotide and cortistatin- 14), but not for native SRIH...
  101. ncbi A cytotoxicity assay for the detection and differentiation of two families of shellfish toxins
    A F Flanagan
    National Diagnostic Centre, BioResearch Ireland, National University of Ireland, Galway, Ireland
    Toxicon 39:1021-7. 2001
    ..This assay should play an important role in shellfish monitoring in the future...

Research Grants65

  1. TOTAL SYNTHESIS OF NATURAL PRODUCTS
    K Nicolaou; Fiscal Year: 2002
    ..3] sigmatropic rearrangement and a radical based ring closure to form the bicyclic skeleton. ..
  2. TOTAL SYNTHESIS OF AZADIRACHTIN
    K Nicolaou; Fiscal Year: 2008
    ..The proposed work is expected to impact the general areas of pharmaceutical and agricultural research, and infectious diseases in particular, through discoveries in synthetic organic chemistry and chemical biology. ..
  3. Enabling Technologies for Combinatorial Chemistry
    K Nicolaou; Fiscal Year: 2005
    ..abstract_text> ..
  4. SYNTHESIS OF ANTICANCER AGENTS
    K C Nicolaou; Fiscal Year: 2010
    ..abstract_text> ..
  5. TOTAL SYNTHESIS OF APOPTOLIDIN
    K Nicolaou; Fiscal Year: 2004
    ..The proposed work is expected to have significant impact in the area of cancer chemotherapy and should provide enabling technologies and tools for biology and medicine. ..
  6. Synthesis of Macrolides, Steroids, Cyclopentanoids, etc.
    BARRY TROST; Fiscal Year: 2009
    ..These new synthetic methods apply to many structural types beyond those illustrated and constitutes a significant to gain access to complex molecular targets more easily. ..
  7. Regulatory Role of Growth Hormone Secretagogue Receptor
    Roy Smith; Fiscal Year: 2007
    ..We hypothesize that clinical use of ghrelin mimetics will translate to improved cognitive function in the elderly. [unreadable] [unreadable] [unreadable]..
  8. Design and Synthesis of HIV-1 Protease Inhibitors
    AMOS SMITH; Fiscal Year: 2004
    ....
  9. NMR systems : 2 Bruker Avance 500 Consoles
    AMOS SMITH; Fiscal Year: 2006
    ..The areas of public health research include, among others, cancer, infectious diseases, neurodegenerative diseases such as Alzheimer's disease, and heart and cardiovascular disease. [unreadable] [unreadable] [unreadable]..
  10. SYNTHESIS OF CHLOROPEPTINS, GP120 CD4 BINDING INHIBITORS
    AMOS SMITH; Fiscal Year: 2001
    ..abstract_text> ..
  11. SYNTHESIS OF SPONGISTATIN ANTITUMOR AGENTS
    AMOS SMITH; Fiscal Year: 2007
    ..abstract_text> ..
  12. TUMOR REMISSION--TAXOL AND CLOSE ANALOGS VIA SYNTHESIS
    LEO PAQUETTE; Fiscal Year: 2003
    ..These include, but are not limited to, the 1-deoxy, D-homo-, 2-desmethyl, and 12-methylene derivatives, in addition to the D-ring invertomer and the C-nor isomer. ..
  13. Synthesis through N-Acylnitrenium Ion Cyclization
    DUNCAN WARDROP; Fiscal Year: 2006
    ..abstract_text> ..
  14. NATURAL PRODUCT SYNTHESIS THROUGH TEMPLATE DIRECTED C-H
    DUNCAN WARDROP; Fiscal Year: 2003
    ..abstract_text> ..
  15. ASYMMETRIC SYNTHESIS OF VANCOMYCIN ANTIBIOTICS
    David Evans; Fiscal Year: 2001
    ..During the course of this project we intend to confirm (correct) the absolute stereochemical assignments of the principal members of this family by total synthesis. ..
  16. ASYMMETRIC SYNTHESIS OF IONOPHORE/MACROLIDE ANTIBIOTICS
    David Evans; Fiscal Year: 2005
    ..Our goal has been to set in place all of the reactions necessary for the rapid assemblage of any polyketide target structure. ..
  17. Synthesis of Polyketides and Terpenes
    David A Evans; Fiscal Year: 2010
    ..As a consequence, organic synthesis is a critical discipline that continues to have an important impact on the fields of both medicine and biology. ..
  18. PHYSIOLOGICALLY ACTIVE NATURAL PRODUCTS
    Douglass Taber; Fiscal Year: 2007
    ..In the course of these investigations, new molecular reactivity will be developed that will substantially shorten current routes to polycyclic natural products and drug candidates. ..
  19. ASYMMETRIC SYNTHESIS OF ANTITUMOR AGENTS
    MICHAEL CRIMMINS; Fiscal Year: 2005
    ..Laulimalide stimulates tubulin polymerization more effectively than paclitaxel. Laulimalide is a representative of a new class of microtubule stabilizing agents with promise for therapeutic potential. ..
  20. Alkynyliodonium Salts and Derived Diyls in Synthesis
    Ken Feldman; Fiscal Year: 2009
    ..abstract_text> ..
  21. UMKC School of Dentistry Oral and Craniofacial Biology
    J Eick; Fiscal Year: 2006
    ..unreadable] [unreadable] [unreadable]..
  22. Molecular Target Focused Discovery of Anticancer Drugs
    George R Pettit; Fiscal Year: 2010
    ....
  23. New Methods for the Synthesis of Neurological Agents
    LARRY OVERMAN; Fiscal Year: 2008
    ..oryzae at 90 nM, suggesting potential antitumor activity. Because of the scarcity of these natural products from their natural sources, little biological evaluation has been carried out. ..
  24. Evaluation in Primates of Cocaine Esterase for the Treatment of Cocaine Toxicity
    Mei Chuan Ko; Fiscal Year: 2010
    ..Dose-response functions for each enzyme will be obtained repeatedly and blood samples analyzed for titer development so that tolerance to the effects of CocE can be monitored. ..
  25. PRACTICAL CHEMICAL SYNTHESIS OF COMPLEX ALKALOIDS
    LARRY OVERMAN; Fiscal Year: 2009
    ....
  26. New Methodology for Indole Alkaloid Syntheses
    Ken S Feldman; Fiscal Year: 2010
    ..The use of a new variant of the Pummerer reaction to control both oxidation level and reaction site within the indole nucleus forms the basis of this chemistry. ..
  27. Molecular Target Focused Discovery of Anticancer Drugs
    GEORGE PETTIT; Fiscal Year: 2007
    ..In summary, the proposed research will be sharply aimed at the discovery and very rapid development of new anticancer drugs for the NCI programs direct at improving human cancer treatments. ..
  28. ASYMMETRIC SYNTHESIS OF NOVEL NATURAL PRODUCTS
    MICHAEL CRIMMINS; Fiscal Year: 2006
    ..Synthesis of the biologically active agents guanacastepene, and SCH 351448 will also be pursued. ..
  29. Micromass LCT Mass Spectrometer
    MICHAEL CRIMMINS; Fiscal Year: 2004
    ..The major users group is highly dependent on rapid turn around mass spectral data. Since there is currently no Departmental mass spectrometry facility, the research programs of the major users have been seriously hampered for some time. ..
  30. SYNTHESIS OF NATURAL PRODUCTS WITH OXAZOLE MOIETIES
    Peter Wipf; Fiscal Year: 2005
    ..The proposed program represents a multi-dimensional effort to increase the basic knowledge of the function of marine natural products, establish new methods in heterocyclic chemistry, and identify novel pharmacophores. ..
  31. SYNTHESIS OF THE TEDANOLIDES, CYTOTOXIC POLYPROPIONATES
    Michael Jung; Fiscal Year: 2003
    ....
  32. Chemical and Biological Studies on Biaryl Phenolics
    Ken Feldman; Fiscal Year: 2005
    ..The search for selective 20S proteosome inhibitors among the Ntn-type proteases will be advanced by these investigations. ..
  33. Intrathecal Opioid-Induced Pruritus
    Mei Chuan Ko; Fiscal Year: 2003
    ..These studies would provide a systematic understanding of the pharmacology of intrathecal morphine-induced pruritus in primates and establish the basis for identifying potential therapeutically effective antipruritics. ..
  34. Silyl Migration-Mediated Tandem Bond Formations
    William Moser; Fiscal Year: 2003
    ..On the basis of these results, a study of stereoselective silyl migration-mediated Baylis-Hillman reactions is proposed, along with the application of the method towards solid-phase synthesis. ..
  35. Nicotinic-Antipsychotic Drug Interactions and Cognition
    Edward Levin; Fiscal Year: 2006
    ..abstract_text> ..
  36. SK Channel Openers as Therapeutics for Cerebellar Ataxia
    Heike Wulff; Fiscal Year: 2007
    ..Taken together these important proof-of-concept studies will help to determine whether SK channel openers constitute a new therapeutic approach to improve motor performance in dominant cerebellar ataxias. ..
  37. Current Design Issues in Oncology Trials
    Anastasia Ivanova; Fiscal Year: 2008
    ..The goal is to develop a study design to identify the dose with a target weighted average of the rates of different toxicity grades. (4) The fourth setting is a genome-wide association study. [unreadable] [unreadable] [unreadable]..
  38. Marine Toxin Impacts on Neurobehavioral Function
    Edward Levin; Fiscal Year: 2003
    ..The forum will provide an opportunity for methodological and theoretical issues to be integrated in the context of each talk as well as in a discussion session at the end of the symposium. ..
  39. Direct Determination of Lower Extremity of Muscle Design
    Richard Lieber; Fiscal Year: 2009
    ..This data, once available to the biomechanical community will propel this field to the next level and enable development of meaningful new surgical procedures and objective methods of evaluating human musculoskeletal function. ..
  40. SYNTHESIS OF BIOACTIVE MACROLIDES
    James White; Fiscal Year: 2002
    ..These pathways, regardless of whether they are successful, must also serve as paradigms for accessing other potentially useful chemotherapeutic agents of equal or greater complexity. ..
  41. Behavioral Genetics and Toxic Response
    Edward Levin; Fiscal Year: 2002
    ....
  42. Mechanisms of Associative Learning in Aging: Mouse Models
    Diana S Woodruff Pak; Fiscal Year: 2010
    ..This proposal has the potential to expand perspectives and devise treatments to facilitate learning and memory in older adults. ..
  43. Halogenated Alkenes and Microsomal GSH-transferases
    Michael J Kelner; Fiscal Year: 2010
    ..4] To determine the relative contribution of MGST1 and MGST2 to cellular antioxidant capacity through studies utilizing human MGST1 and MGST2 null cells. ..
  44. BIOCHEMICAL REGULATORS OF BLEOMYCIN INDUCED TUMORS
    JOHN LAZO; Fiscal Year: 2001
    ..The Specific Aims are to: 1) develop cells and mice deficient in BH, 2) develop cells and mice that overexpress BH, 3) isolate and characterize potential proteins that interact with BH and, 4) analyze the regulation of BH expression. ..
  45. THIOREDOXIN REDUCTASES AND CANCER
    Garth Powis; Fiscal Year: 2001
    ....
  46. DESIGN AND SYNTHESIS OF NONPEPTIDE PROTEASE INHIBITORS
    Arun K Ghosh; Fiscal Year: 2010
    ..This research integrates organic synthesis, protein-ligand x-ray crystallography, molecular modeling and in-depth virus and cell-biological studies to design the next generation of HIV-1 protease inhibitors. ..
  47. INTRAOPERATIVE MEASUREMENT IN CEREBRAL PALSY SURGERY
    Richard Lieber; Fiscal Year: 2003
    ..In addition, these data will be relevant to management of other disorders such as stroke, head injury and spinal cord injury, where surgical tendon transfers are performed. ..
  48. SYNTHESIS OF ANNONACEOUS ACETOGENINS AND ANALOGUES
    James Marshall; Fiscal Year: 2001
    ..The synthetic approach will employ chiral allylic and allenic organometal reagents to introduce stereogenic centers with concurrent formation of carbon-carbon bonds. ..
  49. Adolescence: A Sensitive Period for Nicotine Addiction
    Edward Levin; Fiscal Year: 2008
    ..unreadable] [unreadable]..
  50. Chemical Complementation Assay for MKP-3 (RMI)
    JOHN LAZO; Fiscal Year: 2005
    ..This proposal will provide sufficient reagents, including cells and DMA transfection vectors, to permit the high throughput screening of 100,000 compounds. ..
  51. In Vitro High Throughput Screening Assay for MKP-3(RMI)
    JOHN LAZO; Fiscal Year: 2005
    ..Nonetheless, no potent or selective small molecule inhibitors of this protein phosphatase have been identified. This proposal will provide sufficient reagents to permit a high throughput screening of 100,000 compounds ..
  52. COORDINATED REGULATION OF ANTIOXIDANT ENZYMES
    Michael Kelner; Fiscal Year: 2005
    ..abstract_text> ..
  53. SYNTHESIS OF BIOACTIVE ALKALOIDS
    James White; Fiscal Year: 2006
    ..A plan is presented for the synthesis of this complex heptacyclic molecule which envisions a thio-Claisen rearrangement as the key step for building the vicinal quaternary carbons of this structure. ..
  54. INTERESTING BIOACTIVE SUBSTANCES
    David Williams; Fiscal Year: 2006
    ..The selective synthesis of contiguous stereotriads will advance basic methodology for asymmetric conjugate additions. ..
  55. Survival Signals for Molecular Target Assessment
    Garth Powis; Fiscal Year: 2006
    ..The work will provide important insights into the way these new types of agents can be developed and how their clinical trial should be conducted. ..
  56. Clofarabine: Cytarabine Activation for Leukemia Response
    Stefan Faderl; Fiscal Year: 2004
    ..abstract_text> ..
  57. Bleomycin Hydrolase and Alzheimer's Disease
    JOHN LAZO; Fiscal Year: 2004
    ..These studies should provide new mechanistic information concerning the pathogenesis of AD as well as reagents for future therapeutic studies. ..
  58. Tandem Cycloaddition Chemistry of 2-Azoniaheterodienes
    SCOTT DENMARK; Fiscal Year: 2007
    ..abstract_text> ..
  59. Skeletal Muscle Injury: Mechanism Prevention & Treatment
    Richard Lieber; Fiscal Year: 2007
    ..These studies not only provide insights into the damage mechanism, but also shed light on important structure-function relationships in normal muscle. ..
  60. Synthesis of Tumor Inhibitory Marine Natural Products
    James Marshall; Fiscal Year: 2004
    ..The main chemical issues to be addressed include the control of stereochemistry by means of chiral organometal chemistry and the design of new and efficient routes to structurally novel natural products. ..
  61. Aging and Sites of Action of Cognition-Enhancing Drugs
    DIANA WOODRUFF PAK; Fiscal Year: 2008
    ..These studies will likely support hypotheses about ACh mechanisms in learning and memory and may identify the cerebellum as an additional site of drug action. [unreadable] [unreadable]..
  62. IDENTIFICATION OF NEURONAL RECEPTOR SUBUNITS IN KIDNEY
    RICK SCHNELLMANN; Fiscal Year: 2001
    ..abstract_text> ..
  63. A General Synthetic Route to Glycosidase Inhibitors
    Aaron Aponick; Fiscal Year: 2006
    ....
  64. MITOCHONDRIAL CALPAIN MEDIATED RENAL CELL DEATH
    RICK SCHNELLMANN; Fiscal Year: 2007
    ..Ultimately, these studies may lead to the development of therapeutic agents that improve clinical outcomes in patients with ARF. [unreadable] [unreadable]..