R Pellicciari

Summary

Affiliation: University of Perugia
Country: Italy

Publications

  1. ncbi Metabotropic glutamate receptors: structure and new subtype-selective ligands
    R Pellicciari
    Dipartimento di Chimica e Tecnologia del Farmaco, Perugia, Italy
    Farmaco 56:91-4. 2001
  2. ncbi Farnesoid X receptor: from structure to potential clinical applications
    Roberto Pellicciari
    Dipartimento di Chimica e Tecnologia del Farmaco, , Via del Liceo 1, I-06123 Perugia, Italy
    J Med Chem 48:5383-403. 2005
  3. ncbi Discovery of 6alpha-ethyl-23(S)-methylcholic acid (S-EMCA, INT-777) as a potent and selective agonist for the TGR5 receptor, a novel target for diabesity
    Roberto Pellicciari
    Dipartimento di Chimica e Tecnologia del Farmaco, Universita di Perugia, 06123 Perugia, Italy
    J Med Chem 52:7958-61. 2009
  4. ncbi Back door modulation of the farnesoid X receptor: design, synthesis, and biological evaluation of a series of side chain modified chenodeoxycholic acid derivatives
    Roberto Pellicciari
    Dipartimento di Chimica e Tecnologia del Farmaco, Universita di Perugia, Via del Liceo, 1, 06123 Perugia, Italy
    J Med Chem 49:4208-15. 2006
  5. ncbi Synthesis and preliminary biological evaluation of 2'-substituted 2-(3'-carboxybicyclo[1.1.1]pentyl)glycine derivatives as group I selective metabotropic glutamate receptor ligands
    Roberto Pellicciari
    Dipartimento di Chimica e Tecnologia del Farmaco, Universita di Perugia, Via del Liceo, 1 06123 Perugia, Italy
    ChemMedChem 1:358-65. 2006
  6. ncbi Modulators of the kynurenine pathway of tryptophan metabolism: synthesis and preliminary biological evaluation of (S)-4-(ethylsulfonyl)benzoylalanine, a potent and selective kynurenine aminotransferase II (KAT II) inhibitor
    Roberto Pellicciari
    Dipartimento di Chimica e Tecnologia del Farmaco, , Via del Liceo 1, 06123 Perugia, Italy
    ChemMedChem 1:528-31. 2006
  7. ncbi Nongenomic actions of bile acids. Synthesis and preliminary characterization of 23- and 6,23-alkyl-substituted bile acid derivatives as selective modulators for the G-protein coupled receptor TGR5
    Roberto Pellicciari
    Dipartimento di Chimica e Tecnologia del Farmaco, Universita di Perugia, Via del Liceo 1, 06123 Perugia, Italy
    J Med Chem 50:4265-8. 2007
  8. ncbi Towards new neuroprotective agents: design and synthesis of 4H-thieno[2,3-c] isoquinolin-5-one derivatives as potent PARP-1 inhibitors
    Roberto Pellicciari
    Dipartimento di Chimica e Tecnologia del Farmaco, Universita degli Studi di Perugia, Via del Liceo 1, I 06123 Perugia, Italy
    Farmaco 58:851-8. 2003
  9. ncbi Bile acid derivatives as ligands of the farnesoid X receptor. Synthesis, evaluation, and structure-activity relationship of a series of body and side chain modified analogues of chenodeoxycholic acid
    Roberto Pellicciari
    Dipartimento di Chimica e Tecnologia del Farmaco, Universita di Perugia, Via del Liceo, 1, 06123 Perugia, Italy
    J Med Chem 47:4559-69. 2004
  10. ncbi Synthesis, molecular modeling studies, and preliminary pharmacological characterization of all possible 2-(2'-sulfonocyclopropyl)glycine stereoisomers as conformationally constrained L-homocysteic acid analogs
    Roberto Pellicciari
    Dipartimento di Chimica e Tecnologia del Farmaco, Universita di Perugia, Via del Liceo, 1 06123 Perugia, Italy
    J Med Chem 50:4630-41. 2007

Collaborators

Detail Information

Publications85

  1. ncbi Metabotropic glutamate receptors: structure and new subtype-selective ligands
    R Pellicciari
    Dipartimento di Chimica e Tecnologia del Farmaco, Perugia, Italy
    Farmaco 56:91-4. 2001
    ..Recent advances in the elucidation of the peculiar molecular architecture of mGluRs and in the design and synthesis of subtype selective ligands are discussed...
  2. ncbi Farnesoid X receptor: from structure to potential clinical applications
    Roberto Pellicciari
    Dipartimento di Chimica e Tecnologia del Farmaco, , Via del Liceo 1, I-06123 Perugia, Italy
    J Med Chem 48:5383-403. 2005
  3. ncbi Discovery of 6alpha-ethyl-23(S)-methylcholic acid (S-EMCA, INT-777) as a potent and selective agonist for the TGR5 receptor, a novel target for diabesity
    Roberto Pellicciari
    Dipartimento di Chimica e Tecnologia del Farmaco, Universita di Perugia, 06123 Perugia, Italy
    J Med Chem 52:7958-61. 2009
    ..Herein we report further lead optimization efforts that have led to the discovery of 6alpha-ethyl-23(S)-methylcholic acid (S-EMCA, INT-777) as a novel potent and selective TGR5 agonist with remarkable in vivo activity...
  4. ncbi Back door modulation of the farnesoid X receptor: design, synthesis, and biological evaluation of a series of side chain modified chenodeoxycholic acid derivatives
    Roberto Pellicciari
    Dipartimento di Chimica e Tecnologia del Farmaco, Universita di Perugia, Via del Liceo, 1, 06123 Perugia, Italy
    J Med Chem 49:4208-15. 2006
    ..We thus demonstrate the possibility of achieving a broad FXR modulation without directly affecting the H12 orientation...
  5. ncbi Synthesis and preliminary biological evaluation of 2'-substituted 2-(3'-carboxybicyclo[1.1.1]pentyl)glycine derivatives as group I selective metabotropic glutamate receptor ligands
    Roberto Pellicciari
    Dipartimento di Chimica e Tecnologia del Farmaco, Universita di Perugia, Via del Liceo, 1 06123 Perugia, Italy
    ChemMedChem 1:358-65. 2006
    ..Compounds 11 and 12 were shown to be competitive group I mGluR antagonists. These results are also discussed in light of docking studies with both the active (closed) and inactive (open) conformations of mGluR1...
  6. ncbi Modulators of the kynurenine pathway of tryptophan metabolism: synthesis and preliminary biological evaluation of (S)-4-(ethylsulfonyl)benzoylalanine, a potent and selective kynurenine aminotransferase II (KAT II) inhibitor
    Roberto Pellicciari
    Dipartimento di Chimica e Tecnologia del Farmaco, , Via del Liceo 1, 06123 Perugia, Italy
    ChemMedChem 1:528-31. 2006
  7. ncbi Nongenomic actions of bile acids. Synthesis and preliminary characterization of 23- and 6,23-alkyl-substituted bile acid derivatives as selective modulators for the G-protein coupled receptor TGR5
    Roberto Pellicciari
    Dipartimento di Chimica e Tecnologia del Farmaco, Universita di Perugia, Via del Liceo 1, 06123 Perugia, Italy
    J Med Chem 50:4265-8. 2007
    ..The present results allow for the first time a pharmacological differentiation of genomic versus nongenomic effects mediated by BA derivatives...
  8. ncbi Towards new neuroprotective agents: design and synthesis of 4H-thieno[2,3-c] isoquinolin-5-one derivatives as potent PARP-1 inhibitors
    Roberto Pellicciari
    Dipartimento di Chimica e Tecnologia del Farmaco, Universita degli Studi di Perugia, Via del Liceo 1, I 06123 Perugia, Italy
    Farmaco 58:851-8. 2003
    ..The unsubstituted derivative TIQ was selected for further characterization and found to be endowed with strong neuroprotective properties in models of cerebral ischemia...
  9. ncbi Bile acid derivatives as ligands of the farnesoid X receptor. Synthesis, evaluation, and structure-activity relationship of a series of body and side chain modified analogues of chenodeoxycholic acid
    Roberto Pellicciari
    Dipartimento di Chimica e Tecnologia del Farmaco, Universita di Perugia, Via del Liceo, 1, 06123 Perugia, Italy
    J Med Chem 47:4559-69. 2004
    ..Although none of the new derivatives is more potent than 6ECDCA, we show here that a wide variability in efficacy, from full agonists to partial antagonists, can be obtained...
  10. ncbi Synthesis, molecular modeling studies, and preliminary pharmacological characterization of all possible 2-(2'-sulfonocyclopropyl)glycine stereoisomers as conformationally constrained L-homocysteic acid analogs
    Roberto Pellicciari
    Dipartimento di Chimica e Tecnologia del Farmaco, Universita di Perugia, Via del Liceo, 1 06123 Perugia, Italy
    J Med Chem 50:4630-41. 2007
    ..The library of SCGs (8-15), while providing a novel source of modulators of the glutamate receptors, represents a valuable chemical tool to better characterize L-HCA pathways in the CNS...
  11. ncbi On the way to selective PARP-2 inhibitors. Design, synthesis, and preliminary evaluation of a series of isoquinolinone derivatives
    Roberto Pellicciari
    Dipartimento di Chimica e Tecnologia del Farmaco, Universita di Perugia, Via del Liceo 1, 06123 Perugia, Italy
    ChemMedChem 3:914-23. 2008
    ..Among them, we identified the 5-benzoyloxyisoquinolin-1(2 H)-one derivative as the most selective PARP-2 inhibitor reported so far, with a PARP-2/PARP-1 selectivity index greater than 60...
  12. ncbi Spiro[2.2]pentane as a dissymmetric scaffold for conformationally constrained analogues of glutamic acid: focus on racemic 1-aminospiro[2.2]pentyl-1,4-dicarboxylic acids
    Roberto Pellicciari
    Dipartimento di Chimica e Tecnologia del Farmaco, Universita di Perugia, Via del Liceo, 1, 06123 Perugia Italy
    J Org Chem 67:5497-507. 2002
    ..2]pentyl-1,4-dicarboxylic acid racemic pairs is reported along with their stereochemical assignment, conformational analysis, and preliminary biological evaluation as potential glutamate (ionotropic and metabotropic) ligands...
  13. ncbi Sequence variants in kynurenine aminotransferase II (KAT II) orthologs determine different potencies of the inhibitor S-ESBA
    Roberto Pellicciari
    Dipartimento di Chimica e Tecnologia del Farmaco, University of Perugia, Via del Liceo 1, 06123 Perugia, Italy
    ChemMedChem 3:1199-202. 2008
  14. ncbi Synthesis and preliminary evaluation of (S)-2-(4'-carboxycubyl)glycine, a new selective mGluR1 antagonist
    R Pellicciari
    Istituto di Chimica e Tecnologia del Farmaco, Universita degli Studi, Perugia, Italy
    Bioorg Med Chem Lett 8:1569-74. 1998
    ..S-2-(4'-Carboxy-cubyl)glycine is a structurally novel group I selective antagonist for mGluR1 subtype...
  15. ncbi (2R,1'S,2'R,3'S)-2-(2'-Carboxy-3'-phenylcyclopropyl)glycine (PCCG-13), the first potent and selective competitive antagonist of phospholipase D-coupled metabotropic glutamate receptors: asymmetric synthesis and preliminary biological properties
    R Pellicciari
    Istituto di Chimica e Tecnologia del Farmaco, Universita di Perugia, Via del Liceo, 1 06123 Perugia, Italy
    J Med Chem 42:2716-20. 1999
    ..PCCG-13 is therefore a useful tool for the exploration of the physiopathological role of this novel class of receptors...
  16. ncbi Design, synthesis and preliminary evaluation of novel 3'-substituted carboxycyclopropylglycines as antagonists at group 2 metabotropic glutamate receptors
    R Pellicciari
    Dipartimento di Chimica e Tecnologia del Farmaco, Universita di Perugia, Via del Liceo 1, 06127, Perugia, Italy
    Bioorg Med Chem Lett 11:3179-82. 2001
    ..Compound 8b showed to be a potent group II antagonist with submicromolar activity...
  17. ncbi Metabotropic G-protein-coupled glutamate receptors as therapeutic targets
    R Pellicciari
    Istituto di Chimica e Tecnologia del Farmaco, Via del Liceo 1, I 06123, Perugia, Italy
    Curr Opin Chem Biol 3:433-40. 1999
    ....
  18. ncbi Synthesis and preliminary biological evaluation of (2S,1'R,2'S)- and (2S,1'S,2'R)-2-(2'-phosphonocyclopropyl)glycines, two novel conformationally constrained l-AP4 analogues
    Laura Amori
    Dipartimento di Chimica e Tecnologia del Farmaco, , Via del Liceo, 1-06123 Perugia, Italy
    Bioorg Med Chem Lett 16:196-9. 2006
    ..Compound 7 showed to be a group III mGluRs agonist with micromolar activity...
  19. ncbi Synthesis and biological evaluation of 2-(3'-(1H-tetrazol-5-yl) bicyclo[1.1.1]pent-1-yl)glycine (S-TBPG), a novel mGlu1 receptor antagonist
    G Costantino
    Dipartimento di Chimica e Tecnologia del Farmaco, , Italy
    Bioorg Med Chem 9:221-7. 2001
    ..The interesting biological profile of S-TBPG, coupled with its peculiar chemical structure, is discussed in terms of the structure activity relationship (SAR) of mGluR1 antagonists...
  20. ncbi Charting the chemical space of target sites: insights into the binding modes of amine and amidine groups
    Antonio Macchiarulo
    Dipartimento di Chimica e Tecnologia del Farmaco, Universita di Perugia, Via del Liceo 1, 06127 Perugia, Italy
    J Chem Inf Model 49:900-12. 2009
    ..In addition, this study pinpoints that different types of interactions and bioisosteric relationships exist among primary, secondary, tertiary, quaternary amine, and amidine moieties...
  21. ncbi Synthesis and preliminary pharmacological evaluation of the four stereoisomers of (2S)-2-(2'-phosphono-3'-phenylcyclopropyl)glycine, the first class of 3'-substituted trans C1'-2'-2-(2'-phosphonocyclopropyl)glycines
    Maura Marinozzi
    Dipartimento di Chimica e Tecnologia del Farmaco, Universita di Perugia, Via del Liceo, 1 I 06123 Perugia, Italy
    Bioorg Med Chem 15:3161-70. 2007
    ..The (2S,1'R,2'S,3'R)-isomer (PPCG-2) showed to be a group III mGluRs selective ligand endowed with a moderate potency as mGluR4/mGluR6 agonist...
  22. ncbi Synthesis and preliminary biological evaluation at the glycineB site of (+)- and (-)-3-oxetanylglycine, novel non-proteinogenic amino acids
    M C Terán Moldes
    Dipartimento di Chimica e Tecnologia del Farmaco, Universita degli Studi di Perugia, Italy
    Farmaco 56:609-13. 2001
    ..The lack of activity of these compounds at concentrations up to 100 microM may help in understanding the topological requirements of the glycine site of the NMDA receptor complex...
  23. ncbi Modeling of poly(ADP-ribose)polymerase (PARP) inhibitors. Docking of ligands and quantitative structure-activity relationship analysis
    G Costantino
    Dipartimento di Chimica e Tecnologia del Farmaco, , Via del Liceo 1, 06127 Perugia, Italy
    J Med Chem 44:3786-94. 2001
    ..This information will be useful to address the design of new selective and potent PARP inhibitors...
  24. ncbi Quantum mechanics/molecular mechanics (QM/MM) modeling of the irreversible transamination of L-kynurenine to kynurenic acid: the round dance of kynurenine aminotransferase II
    Daniele Bellocchi
    Dipartimento di Chimica e Tecnologia del Farmaco, Via del Liceo 1, 06123 Perugia, Italy
    Biochim Biophys Acta 1794:1802-12. 2009
    ..Ultimately, they will also be of value in the future design of new KAT-II selective inhibitors...
  25. ncbi Binding mode of 6ECDCA, a potent bile acid agonist of the farnesoid X receptor (FXR)
    Gabriele Costantino
    Dipartimento di Chimica e Tecnologia del Farmaco, , Via del Liceo 1, 06123 Perugia, Italy
    Bioorg Med Chem Lett 13:1865-8. 2003
    ..The results of the docking experiments give quite clear indications that the bile acid derivative would bind the receptor in a mode significantly different than that observed for agonists of other nuclear receptor superfamily...
  26. ncbi Is antagonism of E/Z-guggulsterone at the farnesoid X receptor mediated by a noncanonical binding site? A molecular modeling study
    Udo Meyer
    Dipartimento di Chimica e Tecnologia del Farmaco, Universita di Perugia, Via del Liceo 1, I 06123 Perugia, Italy
    J Med Chem 48:6948-55. 2005
    ..This novel binding pocket may explain some of the peculiar characteristics of 1 when acting at FXR...
  27. ncbi The farnesoid X receptor promotes adipocyte differentiation and regulates adipose cell function in vivo
    Giovanni Rizzo
    Dipartimento di Medicina Clinica e Sperimentale, University of Perugia, Via E dal Pozzo, 06122 Perugia, Italy
    Mol Pharmacol 70:1164-73. 2006
    ..Taken together, these results suggest that activation of FXR plays a critical role in regulating adipogenesis and insulin signaling...
  28. ncbi Highlights at the gate of tryptophan catabolism: a review on the mechanisms of activation and regulation of indoleamine 2,3-dioxygenase (IDO), a novel target in cancer disease
    Antonio Macchiarulo
    Dipartimento di Chimica e Tecnologia del Farmaco, Universita di Perugia, Via del Liceo 1, 06123 Perugia, Italy
    Amino Acids 37:219-29. 2009
    ..Furthermore, we discuss the recent advances of medicinal chemistry in the field of IDO inhibitors...
  29. ncbi Synthesis and biological evaluation of (2S)- and (2R)-2-(3'-phosphonobicyclo[1.1.1]pentyl)glycines as novel group III selective metabotropic glutamate receptor ligands
    Rosanna Filosa
    Dipartimento di Chimica e Tecnologia del Farmaco, , Via del Liceo, 1- 06123 Perugia, Italy
    Bioorg Med Chem 14:3811-7. 2006
    ..The two isomers were tested for their activity against an array of metabotropic glutamate receptors, and the S-isomer (10) turned out to be a moderately potent and selective mGluR4 agonist...
  30. ncbi The role of electrostatic interaction in the molecular recognition of selective agonists to metabotropic glutamate receptors
    Antonio Macchiarulo
    Dipartimento di Chimica e Tecnologia del Farmaco, , 06123 Perugia, Italy
    Proteins 50:609-19. 2003
    ....
  31. ncbi Molecular field analysis and 3D-quantitative structure-activity relationship study (MFA 3D-QSAR) unveil novel features of bile acid recognition at TGR5
    Antonio Macchiarulo
    Dipartimento di Chimica e Tecnologia del Farmaco, Universita di Perugia, Via del Liceo 1, 06123 Perugia, Italy
    J Chem Inf Model 48:1792-801. 2008
    ..This information is instrumental to extend on a quantitative basis the current structure-activity relationships of bile acids as TGR5 modulators and will be fruitful to design new potent and selective agonists of the receptor...
  32. ncbi Dynamic ligand-exchange chiral stationary phase from S-benzyl-(R)-cysteine
    B Natalini
    Universita degli Studi di Perugia, Dipartimento di Chimica e Tecnologia del Farmaco, Perugia, Italy
    Chirality 18:509-18. 2006
    ....
  33. ncbi QSAR and molecular modeling studies of baclofen analogues as GABA(B) agonists. Insights into the role of the aromatic moiety in GABA(B) binding and activation
    G Costantino
    Dipartimento di Chimica e Tecnologia del Farmaco, , Via del Liceo 1, 06123 Perugia, Italy
    J Med Chem 44:1827-32. 2001
    ..These results are discussed in terms of mechanism of GABA(B) activation promoted by baclofen or GABA...
  34. ncbi 3alpha-6alpha-Dihydroxy-7alpha-fluoro-5beta-cholanoate (UPF-680), physicochemical and physiological properties of a new fluorinated bile acid that prevents 17alpha-ethynyl-estradiol-induced cholestasis in rats
    Carlo Clerici
    Clinica di Gastroenterologia ed Epatologia, Dipartimento di Medicina Clinica e Sperimentale Università degli Studi di Perugia, 06122 Perugia, Italy
    Toxicol Appl Pharmacol 214:199-208. 2006
    ..This novel fluorinated bile acid may have potential in the treatment of cholestatic liver disease...
  35. ncbi Computational studies for the elucidation of the enantiomer elution order of amino acids in chiral ligand-exchange chromatography
    Benedetto Natalini
    Department of Chemistry and Technology of Drugs, Via del Liceo 1, 06123 Perugia, Italy
    J Chromatogr A 1217:7523-7. 2010
    ..The profitable predictive power of the developed model was assessed on the selected test set (5 species)...
  36. ncbi Descriptive structure-separation relationship studies in chiral ligand-exchange chromatography
    Benedetto Natalini
    Dipartimento di Chimica e Tecnologia del Farmaco, Universita degli Studi di Perugia, Perugia, Italy
    J Sep Sci 31:2395-403. 2008
    ..While fractional negatively charged partial surface area (FNSA-3) results the discriminating descriptor for (R)-enantiomers, the relative polar surface area (RPSA) is able to best discriminate among (S)-enantiomers...
  37. ncbi Chiral ligand-exchange separation and resolution of extremely rigid glutamate analogs: 1-aminospiro[2.2]pentyl-1,4-dicarboxylic acids
    Benedetto Natalini
    Dipartimento di Chimica e Tecnologia del Farmaco, Universita degli Studi di Perugia, Via del Liceo 1, 06123, Perugia, Italy
    Anal Bioanal Chem 397:1997-2011. 2010
    ..The validated analytical method was then fruitfully adopted for semi-preparative-scale isolation of the enantiomers of ASPED C...
  38. ncbi Alternative strategies for targeting mouse double minute 2 activity with small molecules: novel patents on the horizon?
    Antonio Macchiarulo
    Expert Opin Ther Pat 21:287-94. 2011
    ..It is likely that settling some open issues such as the site of action of these compounds and their specificity towards E3 ligase enzymes will open in the near feature new horizons in cancer therapy...
  39. ncbi Side-chain modified bile acids: chromatographic separation of 23-methyl epimers
    Benedetto Natalini
    Dipartimento di Chimica e Tecnologia del Farmaco, Universita degli Studi di Perugia, Perugia, Italy
    J Sep Sci 32:2022-33. 2009
    ..Moreover, the engagement of an evaporative light scattering detector (ELSD) has proven its high effectiveness for the analysis of such steroidal species...
  40. ncbi (S)-(-)-alpha,alpha-Di(2-naphthyl)-2-pyrrolidinemethanol, a useful tool to study the recognition mechanism in chiral ligand-exchange chromatography
    Benedetto Natalini
    Dipartimento di Chimica e Tecnologia del Farmaco, Universita degli Studi di Perugia, Perugia, Italy
    J Sep Sci 30:21-7. 2007
    ....
  41. ncbi The effect of the copper(II) salt anion in the Chiral Ligand-Exchange Chromatography of amino acids
    Benedetto Natalini
    Dipartimento di Chimica e Tecnologia del Farmaco, Universita di Perugia, Via del Liceo 1, 06123 Perugia, Italy
    Anal Chim Acta 638:225-33. 2009
    ..Even if to a lesser extent, the enantioseparation factor values (alpha) underwent variation, as well. A molecular modelling investigation has also been carried out as a rationalization attempt of the observed chromatographic outcomes...
  42. ncbi Correlation between CMC and chromatographic index: simple and effective evaluation of the hydrophobic/hydrophilic balance of bile acids
    Benedetto Natalini
    Dipartimento di Chimica e Tecnologia del Farmaco, Universita degli Studi di Perugia, Via del Liceo, 1, 06123, Perugia, Italy
    Anal Bioanal Chem 388:1681-8. 2007
    ..The correlation of the CMC with the derived chromatographic hydrophobic index phi0 was satisfactory...
  43. ncbi Molecular docking and spatial coarse graining simulations as tools to investigate substrate recognition, enhancer binding and conformational transitions in indoleamine-2,3-dioxygenase (IDO)
    Antonio Macchiarulo
    Dipartimento di Chimica e Tecnologia del Farmaco, Universita di Perugia, Via del Liceo 1, 06123 Perugia, Italy
    Biochim Biophys Acta 1774:1058-68. 2007
    ..On this basis, a molecular mechanism regarding substrate recognition and activity enhancement by indole derivatives is proposed...
  44. ncbi Derived chromatographic indices as effective tools to study the self-aggregation process of bile acids
    Benedetto Natalini
    Universita degli Studi di Perugia, Dipartimento di Chimica e Tecnologia del Farmaco, Via del Liceo, 1, 06123 Perugia, Italy
    J Pharm Biomed Anal 50:613-21. 2009
    ..Molecular modelling studies have also been undertaken with the aim of rationalizing the experimental findings...
  45. ncbi S-trityl-(R)-cysteine, a powerful chiral selector for the analytical and preparative ligand-exchange chromatography of amino acids
    Benedetto Natalini
    Dipartimento di Chimica e Tecnologia del Farmaco, Universita degli Studi di Perugia, Perugia, Italy
    J Sep Sci 31:696-704. 2008
    ..The relatively easy removal of the Cu(II) ions renders this technique suitable for obtaining small amounts of enantiomerically pure samples for preliminary biological evaluations...
  46. ncbi Cysteine-based chiral selectors for the ligand-exchange separation of amino acids
    Benedetto Natalini
    Dipartimento di Chimica e Tecnologia del Farmaco, Universita degli Studi di Perugia, Via del Liceo 1, 06123 Perugia, Italy
    J Chromatogr B Analyt Technol Biomed Life Sci 875:108-17. 2008
    ....
  47. ncbi QSAR study of anticonvulsant negative allosteric modulators of the AMPA receptor
    Antonio Macchiarulo
    Dipartimento di Chimica e Tecnologia del Farmaco, , Via del Liceo 1 06123 Perugia, Italy
    J Med Chem 47:1860-3. 2004
    ....
  48. ncbi Modulation of the kynurine pathway of tryptophan metabolism in search for neuroprotective agents. Focus on kynurenine-3-hydroxylase
    Roberto Pellicciari
    Dipartimento di Chimica e Tecnologia del Farmaco, , Via del Liceo 1, 06123 Perugia, Italy
    Adv Exp Med Biol 527:621-8. 2003
    ..These data support the notion that kynurenine-3-hydroxylase inhibitors may have a sustained therapeutic potential in those diseases characterized by unbalance in the QUIN/KYNA branches of the kynurenine pathway...
  49. ncbi Evaluation of the enantiomeric selectivity in the chiral ligand-exchange chromatography of amino acids by a computational model
    Benedetto Natalini
    Dipartimento di Chimica e Tecnologia del Farmaco, Universita degli Studi di Perugia, Via del Liceo 1, 06123 Perugia, Italy
    J Chromatogr A 1033:363-7. 2004
    ..The elution order seems to be related to the different water coordination capability on copper ion in the formation of the mixed ternary complexes...
  50. ncbi Molecular dynamics simulation of the ligand binding domain of farnesoid X receptor. Insights into helix-12 stability and coactivator peptide stabilization in response to agonist binding
    Gabriele Costantino
    Dipartimento di Chimica e Tecnologia del Farmaco, Universita di Perugia, Via del Liceo 1, 06123 Perugia, Italy
    J Med Chem 48:3251-9. 2005
    ..The present results provide a molecular basis for the understanding the role played by the bile acid agonist in receptor stabilization and enhanced cofactor recruitments...
  51. ncbi Preparative resolution of 1-aminoindan-1,5-dicarboxylic acid (AIDA) by chiral ligand-exchange chromatography
    Benedetto Natalini
    Universita degli Studi di Perugia, Dipartimento di Chimica e Tecnologia del Farmaco, Perugia, Italy
    Chirality 16:314-7. 2004
    ..In functional activity experiments, only (S)-AIDA was a potent and mGluR1 subtype selective antagonist...
  52. ncbi Molecular dynamics simulation of the ligand binding domain of mGluR1 in response to agonist and antagonist binding
    Gabriele Costantino
    Dipartimento di Chimica e Tecnologia del Farmaco, Universita di Perugia, Via del Liceo 1, 06123 Perugia, Italy
    J Comput Aided Mol Des 16:779-84. 2002
    ..Analysis of the ligand behavior over time allows to delineate some of the molecular determinants responsible for the agonist-induced or antagonist-blocked LBD responses...
  53. ncbi A farnesoid x receptor-small heterodimer partner regulatory cascade modulates tissue metalloproteinase inhibitor-1 and matrix metalloprotease expression in hepatic stellate cells and promotes resolution of liver fibrosis
    Stefano Fiorucci
    Dept of Clinical and Experimental Medicine, University of Perugia, Policlinico Monteluce, Via E dal Pozzo, 06122 Perugia, Italy
    J Pharmacol Exp Ther 314:584-95. 2005
    ..By demonstrating that a FXR-SHP regulatory cascade promotes the development of a quiescent phenotype and increases apoptosis of HSCs, this study establishes that FXR ligands may be beneficial in treatment of liver fibrosis...
  54. ncbi Cross-talk between farnesoid-X-receptor (FXR) and peroxisome proliferator-activated receptor gamma contributes to the antifibrotic activity of FXR ligands in rodent models of liver cirrhosis
    Stefano Fiorucci
    Dipartimento de Medicina Clinica e Sperimentale, Universita degli Studi di Perugia, Italy
    J Pharmacol Exp Ther 315:58-68. 2005
    ..A FXR-PPARgamma cascade exerts counter-regulatory effects in HSCs activation...
  55. ncbi The nuclear receptor SHP mediates inhibition of hepatic stellate cells by FXR and protects against liver fibrosis
    Stefano Fiorucci
    Clinica di Gastroenterologia ed Endoscopia Digestiva, Perugia, Italy
    Gastroenterology 127:1497-512. 2004
    ..The aim of this study was to investigate whether FXR is expressed by and modulates function of hepatic stellate cells (HSCs)...
  56. ncbi Protective effects of 6-ethyl chenodeoxycholic acid, a farnesoid X receptor ligand, in estrogen-induced cholestasis
    Stefano Fiorucci
    Gastroenterologia ed Epatologia, Policlinico Monteluce, Perugia, Italy
    J Pharmacol Exp Ther 313:604-12. 2005
    ..In conclusion, by demonstrating that 6-ECDCA protects against E(2)17alpha cholestasis, our data support the notion that development of potent FXR ligands might represent a new approach for the treatment of cholestatic disorders...
  57. ncbi Unveiling hidden features of orphan nuclear receptors: the case of the small heterodimer partner (SHP)
    Antonio Macchiarulo
    Dipartimento di Chimica e Tecnologia del Farmaco, , Via del Liceo 1, 06127 Perugia, Italy
    J Mol Graph Model 24:362-72. 2006
    ....
  58. ncbi Targeting the conformational transitions of MDM2 and MDMX: insights into dissimilarities and similarities of p53 recognition
    Antonio Macchiarulo
    Dipartimento di Chimica e Tecnologia del Farmaco, Universita di Perugia, Via del Liceo 1, Perugia, Italy
    J Chem Inf Model 48:1999-2009. 2008
    ....
  59. ncbi Targeting the conformational transitions of MDM2 and MDMX: insights into key residues affecting p53 recognition
    Andrea Carotti
    Dipartimento di Chimica e Tecnologia del Farmaco, Universita di Perugia, 06123 Perugia, Italy
    Proteins 77:524-35. 2009
    ..The results of this study shed further light on different p53 recognition in MDM2 and MDMX and may prove useful for the design and identification of new potent and selective synthetic modulators of p53-MDM2/MDMX interactions...
  60. ncbi Exploring the other side of biologically relevant chemical space: insights into carboxylic, sulfonic and phosphonic acid bioisosteric relationships
    Antonio Macchiarulo
    Dipartimento di Chimica e Tecnologia del Farmaco, Universita di Perugia, Via del Liceo 1, 06123 Perugia, Italy
    J Mol Graph Model 26:728-39. 2007
    ....
  61. ncbi Pharmacophore model for bile acids recognition by the FPR receptor
    Cristina Ferrari
    Dipartimento di Chimica e Tecnologia del Farmaco, , Via del Liceo 1, 06127 Perugia, Italy
    J Comput Aided Mol Des 20:295-303. 2006
    ..A closer inspection of bile acid interaction reveals a number of unexploited anchor points in the binding site that may be used to aid the design of new potent and selective bile acids derivatives at FPR...
  62. ncbi Molecular interaction fields and 3D-QSAR studies of p53-MDM2 inhibitors suggest additional features of ligand-target interaction
    Cristina Dezi
    Dipartimento di Chimica e Tecnologia del Farmaco, Universita di Perugia, Via del Liceo 1, 06123 Perugia, Italy
    J Chem Inf Model 50:1451-65. 2010
    ....
  63. ncbi An efficient procedure for the regiospecific preparation of D-homo-steroid derivatives
    R Pellicciari
    Istituto di Chimica Farmaceutica e Tecnica Farmaceutica, Universita degli Studi, Perugia, Italy
    Steroids 49:433-41. 1987
    ....
  64. ncbi MDM2/MDMX inhibitor peptide: WO2008106507
    Antonio Macchiarulo
    Universita di Perugia, Dipartimento di Chimica e Tecnologia del Farmaco, Perugia, Italy
    Expert Opin Ther Pat 19:721-6. 2009
    ....
  65. ncbi 3. Life or death decisions: the cast of poly(ADP-ribose)polymerase (PARP) as a therapeutic target for brain ischaemia
    Roberto Pellicciari
    Dipartimento di Chimica e Tecnologia del Farmaco, Via del Liceo 1, 06123 Perugia, Italy
    Prog Med Chem 42:125-69. 2004
  66. ncbi Docking studies on PARP-1 inhibitors: insights into the role of a binding pocket water molecule
    Daniele Bellocchi
    Dipartimento di Chimica e Tecnologia del Farmaco, , Via del Liceo 1, 06123 Perugia, Italy
    Bioorg Med Chem 13:1151-7. 2005
    ..87) or not (r2=0.84) the structural water molecule. Closer inspection of our results suggested that this water molecule should be considered part of the hydration shell of polar inhibitors and not as a structural water...
  67. ncbi Insights into phenylalanine derivatives recognition of VLA-4 integrin: from a pharmacophoric study to 3D-QSAR and molecular docking analyses
    Antonio Macchiarulo
    Dipartimento di Chimica e Tecnologia del Farmaco, , Via del Liceo 1, 06127 Perugia, Italy
    J Chem Inf Comput Sci 44:1829-39. 2004
    ..Docking experiments of TR-14035 into the binding site of VLA-4 aided the interpretation of the 3D-QSAR model. The obtained results will be fruitful for the design of new potent and selective antagonists of VLA-4...
  68. ncbi 6alpha-ethyl-chenodeoxycholic acid (6-ECDCA), a potent and selective FXR agonist endowed with anticholestatic activity
    Roberto Pellicciari
    J Med Chem 45:3569-72. 2002
    ..Among them, 6alpha-ethyl-chenodeoxycholic acid (6-ECDCA) was shown to be a very potent and selective FXR agonist (EC(50) = 99 nM) and to be endowed with anticholeretic activity in an in vivo rat model of cholestasis...
  69. ncbi Metabotropic glutamate 1 (mGlu1) receptor antagonists enhance GABAergic neurotransmission: a mechanism for the attenuation of post-ischemic injury and epileptiform activity?
    Andrea Cozzi
    Dipartimento di Farmacologia Preclinica e Clinica, Universita di Firenze, Viale Pieraccini 6, 50139 Firenze, Italy
    Neuropharmacology 43:119-30. 2002
    ....
  70. ncbi Binding modes of noncompetitive AMPA antagonists: a computational approach
    Laura De Luca
    Dipartimento Farmaco-Chimico, , Viale Annunziata 98168, Messina, Italy
    Farmaco 58:107-13. 2003
    ..The results suggest that the interdomain cleft of the LIVBP-like domain of AMPAR may contain the noncompetitive antagonist binding pocket...
  71. ncbi Novel isoquinolinone-derived inhibitors of poly(ADP-ribose) polymerase-1: pharmacological characterization and neuroprotective effects in an in vitro model of cerebral ischemia
    Alberto Chiarugi
    Dipartimento di Farmacologia Preclinica e Clinica, , Viale Pieraccini, 6, 50139 Firenze, Italy
    J Pharmacol Exp Ther 305:943-9. 2003
    ..93, P < 0.01) was observed. Our results suggest that TIQ-A and its derivatives are a new class of neuroprotectants that may be helpful in studies aimed at understanding the involvement of PARP-1 in physiology and pathology...
  72. ncbi Endogenous kynurenate controls the vulnerability of striatal neurons to quinolinate: Implications for Huntington's disease
    Michael T Sapko
    Maryland Psychiatric Research Center, University of Maryland School of Medicine, P O Box 21247, Baltimore, MD 21228, USA
    Exp Neurol 197:31-40. 2006
    ..Our data suggest that timely pharmacological interventions resulting in an up-regulation of brain KYNA levels may benefit patients suffering from HD or other neurodegenerative diseases...
  73. ncbi Structural basis for bile acid binding and activation of the nuclear receptor FXR
    Li Zhi Mi
    Department of Pharmacology, University of Virginia Health System, Charlottesville 22908, USA
    Mol Cell 11:1093-100. 2003
    ..These FXR complexes provide direct insights into the design of therapeutic bile acids for treatment of hyperlipidemia and cholestasis...
  74. ncbi The novel and systemically active metabotropic glutamate 1 (mGlu1) receptor antagonist 3-MATIDA reduces post-ischemic neuronal death
    Flavio Moroni
    Dipartimento di Farmacologia Preclinica e Clinica, Universita di Firenze, Viale Pieraccini 6, 50139 Firenze, Italy
    Neuropharmacology 42:741-51. 2002
    ..Our results show that 3-MATIDA is a potent and possibly selective mGlu 1 receptor antagonist that may be considered as a novel prototype neuroprotective agent...
  75. ncbi 7alpha-OH epimerisation of bile acids via oxido-reduction with Xanthomonas maltophilia
    Alessandro Medici
    Dipartimento di Chimica, Universita di Ferrara, Via L Borsari 46, I 44100, Ferrara, Italy
    Steroids 67:51-6. 2002
    ..On the basis of these results a further application is the microbial reduction of 6alpha-fluoro and 6beta-fluoro-3alpha-hydroxy-7-oxo-5beta-cholan-24-oic acid methyl esters to the corresponding 7alpha-OH and 7beta-OH derivatives...
  76. ncbi Novel potent and selective bile acid derivatives as TGR5 agonists: biological screening, structure-activity relationships, and molecular modeling studies
    Hiroyuki Sato
    Institut de Genetique et de Biologie Moleculaire et Cellulaire, Centre National de la Recherche Scientifique INSERM ULP, Illkirch, France
    J Med Chem 51:1831-41. 2008
    ....
  77. ncbi Perinatal kynurenine 3-hydroxylase inhibition in rodents: pathophysiological implications
    Gianpiera Ceresoli Borroni
    Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore, Maryland 21228, USA
    J Neurosci Res 85:845-54. 2007
    ..Selective inhibitors of this enzyme may therefore provide neuroprotection in newborns and will also be useful for the experimental evaluation of the long-term effects of perinatal KP impairment...
  78. ncbi Stereoselective synthesis and preliminary evaluation of (+)- and (-)-3-methyl-5-carboxy-thien-2-yl-glycine (3-MATIDA): identification of (+)-3-MATIDA as a novel mGluR1 competitive antagonist
    Gabriele Costantino
    Dipartimento di Chimica e Tecnologia del Farmaco. Via del Liceo 1, Perugia 06123, Italy
    Farmaco 59:93-9. 2004
    ..The two isomers were tested as potential rat mGluR1 ligand and the (+) isomer was found to be a moderately potent antagonist, while the (-) one was inactive...
  79. ncbi Rat brain guanosine binding site. Biological studies and pseudo-receptor construction
    Ugo Traversa
    Dipartimento di Scienze Biomediche - BRAIN Center, via L Giorgieri 7, , 34127 Trieste, Italy
    Bioorg Med Chem 11:5417-25. 2003
    ..This construct will be useful for the in silico screening of compound libraries in search for new potent and structurally diverse pharmacological tools...
  80. ncbi Role of FXR in regulating bile acid homeostasis and relevance for human diseases
    Giovanni Rizzo
    Dipartimento di Medicina Clinica e Sperimentale, Clinica di Gastroenterologia ed Epatologia, Pergia, Italy
    Curr Drug Targets Immune Endocr Metabol Disord 5:289-303. 2005
    ..In vivo administration of 6-ECDCA protects against cholestasis induced by estrogen and LCA in rats providing evidence that development of potent FXR agonists might represent a new approach for the treatment of cholestastic disorders...
  81. ncbi The methyl transferase PRMT1 functions as co-activator of farnesoid X receptor (FXR)/9-cis retinoid X receptor and regulates transcription of FXR responsive genes
    Giovanni Rizzo
    Clinica di Gastroenterologia ed Endoscopia Digestiva, Policlinico Monteluce, 06100 Perugia, Italy
    Mol Pharmacol 68:551-8. 2005
    ..Our results indicate that histone methylation, similar to acetylation, regulates transcriptional activation of genes involved in cholesterol and BAs homeostasis...
  82. ncbi Targeting bile-acid signalling for metabolic diseases
    Charles Thomas
    Institute of Genetics and Molecular and Cellular Biology, 1 rue Laurent Fries, 67404 Illkirch, France
    Nat Rev Drug Discov 7:678-93. 2008
    ....
  83. ncbi Manipulation of brain kynurenines: glial targets, neuronal effects, and clinical opportunities
    Robert Schwarcz
    Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore, USA
    J Pharmacol Exp Ther 303:1-10. 2002
    ..These compounds can be used to normalize KP defects, show remarkable efficacy in animal models of central nervous system disorders, and offer novel therapeutic opportunities...
  84. ncbi Adamantyl-substituted retinoid-derived molecules that interact with the orphan nuclear receptor small heterodimer partner: effects of replacing the 1-adamantyl or hydroxyl group on inhibition of cancer cell growth, induction of cancer cell apoptosis, and
    Marcia I Dawson
    Cancer Center and Inflammatory and Infectious Disease Center, Burnham Institute for Medical Research, La Jolla, California 92037, USA
    J Med Chem 51:5650-62. 2008
    ..Inhibitory activity against Src homology 2 domain-containing protein tyrosine phosphatase 2 (Shp-2) was also assessed. The most active Shp-2 inhibitor was found to be the 3'-(3,3-dimethylbutynyl) analogue of 3-Cl-AHPC...
  85. ncbi Interfacial properties of most monofluorinated bile acids deviate markedly from the natural congeners: studies with the Langmuir-Pockels surface balance
    John M Kauffman
    Department of Medicine, Harvard Medical School, Harvard Digestive Diseases Center, Brigham and Women's Hospital, Boston, MA, USA
    J Lipid Res 46:571-81. 2005
    ..These results provide a framework for designing F-modified bile acids to mimic or diverge from the natural compounds in vivo...