The 5-HT1A agonism potential of substituted-piperazine-ethyl-amide derivatives is conserved in the hexyl homologues: molecular modeling and pharmacological evaluation
[en] In a series of carboxamide and sulphonamide alkyl (ethyl to hexyl) piperazine analogues, although the size of the linker is very different, ethyl and hexyl derivatives possess a high affinity for 5-HT1A receptors. Docking studies clearly show that hexyl and ethyl compounds favourably interact with the binding site of the active conformation of 5-HT1A receptors, thus confirming a possible agonist profile. This activity is effectively detected in electrophysiological experiments in which all four compounds inhibit the activity of rat dorsal raphe serotonergic neurons.
Research Center/Unit :
Département de pharmacie / Chimie pharmaceutique Giga-Neurosciences / Pharmacologie
Dilly, Sébastien ; Université de Liège - ULiège > Département de Pharmacie / GIGA-Neuroscience > Chimie Pharmaceutique / Pharmacologie
Scuvée-Moreau, Jacqueline ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Pharmacologie
Wouters, Johan; Université de Namur > Département de Chimie
Liégeois, Jean-François ; Université de Liège - ULiège > Département de pharmacie > Chimie pharmaceutique
Language :
English
Title :
The 5-HT1A agonism potential of substituted-piperazine-ethyl-amide derivatives is conserved in the hexyl homologues: molecular modeling and pharmacological evaluation
Publication date :
2011
Journal title :
Journal of Chemical Information and Modeling
ISSN :
1549-9596
eISSN :
1549-960X
Publisher :
American Chemical Society
Volume :
51
Issue :
11
Pages :
2961-2966
Peer reviewed :
Peer Reviewed verified by ORBi
Funders :
F.R.S.-FNRS - Fonds de la Recherche Scientifique ULg FSR - Université de Liège. Fonds spéciaux pour la recherche
Résimont, M.; Liégeois, J.-F. Synthesis and in vitro binding studies of piperazine-alkyl-naphthamides: impact of homology and sulphonamide/carboxamide bioisosteric replacement on the affinity for 5-HT 1A, α2A, D4.2, D3 and D2L receptors Bioorg. Med. Chem. Lett. 2010, 20, 5199-202
Kelly, M. G.; Palmer, Y. L. Piperazine ethylamide derivatives. US Patent 6344458, February 5, 2002.
The UniProt Consortium. Ongoing and future developments at the Universal Protein Resource. Nucleic Acids Res. 2011, 39, D214-D219.
The Universal Protein Resource. http://www.uniprot.org/uniprot/P08908 (accessed November 1, 1988).
The Universal Protein Resource. http://www.uniprot.org/uniprot/P07700 (accessed April 1, 1988).
Shi, J.; Blundell, T. L.; Mizuguchi, K. FUGUE: sequence-structure homology recognition using environment-specific substitution tables and structure-dependent gap penalties J. Mol. Biol. 2001, 310, 243-57 (Pubitemid 32619966)
Baldwin, J. M.; Schertler, G. F.; Unger, V. M. An alpha-carbon template for the transmembrane helices in the rhodopsin family of G-protein-coupled receptors J. Mol. Biol. 1997, 272, 144-64 (Pubitemid 27395544)
Warne, T.; Moukhametzianov, R.; Baker, J. G.; Nehme, R.; Edwards, P. C.; Leslie, A. G.; Schertler, G. F.; Tate, C. G. The structural basis for agonist and partial agonist action on a beta(1)-adrenergic receptor Nature 2011, 469, 241-4
Dilly, S.; Liégeois, J.-F. Interaction of clozapine and its nitrenium ion with rat D2 dopamine receptors: in vitro binding and computational study J. Comput.-Aided Mol. Des. 2011, 25, 163-9
Arvidsson, L. E.; Hacksell, U.; Nilsson, J. L.; Hjorth, S.; Carlsson, A.; Lindberg, P.; Sanchez, D.; Wikstrom, H. 8-Hydroxy-2-(di-n-propylamino)tetralin, a new centrally acting 5-hydroxytryptamine receptor agonist J. Med. Chem. 1981, 24, 921-3 (Pubitemid 11015157)
Dabrowska, J.; Brylinski, M. Stereoselectivity of 8-OH-DPAT toward the serotonin 5-HT1A receptor: biochemical and molecular modeling study Biochem. Pharmacol. 2006, 72, 498-511 (Pubitemid 44061750)
Saunders, M. Stochastic exploration of molecular mechanics energy surfaces. Hunting for the global minimum J. Am. Chem. Soc. 1987, 109, 3150-3152
Ballesteros, J.; Weinstein, H. Integrated methods for the construction of three-dimensional models and computational probing of structure-function relations in G protein coupled receptors Methods Neurosci. 1995, 25, 366-428
Bywater, R. P. Location and nature of the residues important for ligand recognition in G-protein coupled receptors J. Mol. Recognit. 2005, 18, 60-72 (Pubitemid 40059571)
Choudhary, M. S.; Craigo, S.; Roth, B. L. A single point mutation (Phe340 - >Leu340) of a conserved phenylalanine abolishes 4-[125I]iodo- (2,5-dimethoxy)phenylisopropylamine and [3H]mesulergine but not [3H]ketanserin binding to 5-hydroxytryptamine2 receptors Mol. Pharmacol. 1993, 43, 755-61 (Pubitemid 23146275)
Salom, D.; Lodowski, D. T.; Stenkamp, R. E.; Le Trong, I.; Golczak, M.; Jastrzebska, B.; Harris, T.; Ballesteros, J. A.; Palczewski, K. Crystal structure of a photoactivated deprotonated intermediate of rhodopsin Proc. Natl. Acad. Sci. U.S.A. 2006, 103, 16123-8 (Pubitemid 44715162)
Shapiro, D. A.; Kristiansen, K.; Kroeze, W. K.; Roth, B. L. Differential modes of agonist binding to 5-Hydroxytryptamine(2A) serotonin receptors revealed by mutation and molecular modeling of conserved residues in transmembrane region 5 Mol. Pharmacol. 2000, 58, 877-886
Powell, M. J. D. Restart procedures for the conjugate gradient method Math. Program. 1977, 12, 241-254
Weiner, S. J.; Kollman, P. A.; Nguyen, D. T.; Case, D. A. An All Atom Force Field for Simulations of Proteins and Nucleic Acids J. Comput. Chem. 1986, 7, 230-252
Halgren, T. A. Merck molecular force field 0.1. Basis, form, scope, parameterization, and performance of MMFF94 J. Comput. Chem. 1996, 17, 490-519 (Pubitemid 126567067)
Paton, R. S.; Goodman, J. M. Hydrogen bonding and pi-stacking: how reliable are force fields? A critical evaluation of force field descriptions of nonbonded interactions J. Chem. Inf. Model. 2009, 49, 944-55
Laskowski, R. A.; MacArthur, M. W.; Moss, D. S.; Thornton, J. M. PROCHECK: a program to check the stereochemical quality of protein structures J. Appl. Crystallogr. 1993, 26, 283-291
Ho, B. Y.; Karschin, A.; Branchek, T.; Davidson, N.; Lester, H. A. The Role of Conserved Aspartate and Serine Residues in Ligand-Binding and in Function of the 5-Ht(1a) Receptor-a Site-Directed Mutation Study FEBS Lett. 1992, 312, 259-262
Strader, C. D.; Candelore, M. R.; Hill, W. S.; Sigal, I. S.; Dixon, R. A. F. Identification of 2 Serine Residues Involved in Agonist Activation of the Beta-Adrenergic-Receptor J. Biol. Chem. 1989, 264, 13572-13578 (Pubitemid 19198437)
Gasteiger, M.; Marsili, M. Iterative Partial Equalization of Orbital Electronegativity-A Rapid Access to Atomic Charges Tetrahedron 1980, 36, 3219-3228
Purcell, W. P.; Singer, J. A. A brief review and table of semiempirical parameters used in the Hueckel molecular orbital method J. Chem. Eng. Data 1967, 12, 235-246
Jones, G.; Willett, P.; Glen, R. C.; Leach, A. R.; Taylor, R. Development and validation of a genetic algorithm for flexible docking J. Mol. Biol. 1997, 267, 727-48 (Pubitemid 27170693)
Aghajanian, G. K.; Sprouse, J. S.; Sheldon, P.; Rasmussen, K. Electrophysiology of the central serotonin system: receptor subtypes and transducer mechanisms. Ann. N.Y. Acad. Sci. 1990, 600, 93-103; discussion 103.
Forster, E. A.; Cliffe, I. A.; Bill, D. J.; Dover, G. M.; Jones, D.; Reilly, Y.; Fletcher, A. A pharmacological profile of the selective silent 5-HT1A receptor antagonist, WAY-100635 Eur. J. Pharmacol. 1995, 281, 81-8
Defraiteur, C.; Plenevaux, A.; Scuvée-Moreau, J.; Rouchet, N.; Goblet, D.; Luxen, A.; Seutin, V. Characterization of 4-(2-hydroxyphenyl)-1- [2′-[N-(2′-pyridinyl)-p-fluorobenzamido]ethyl]piperazine (p-DMPPF) as a new potent 5-HT1A antagonist Br. J. Pharmacol. 2007, 152, 952-8 (Pubitemid 350100490)
Vandermaelen, C. P.; Aghajanian, G. K. Electrophysiological and pharmacological characterization of serotonergic dorsal raphe neurons recorded extracellularly and intracellularly in rat brain slices Brain Res. 1983, 289, 109-19 (Pubitemid 14222511)
Vandermaelen, C. P.; Aghajanian, G. K. Electrophysiological and pharmacological characterization of serotonergic dorsal raphe neurons recorded extracellularly and intracellularly in rat brain slices Brain Res. 1983, 289, 109-19 (Pubitemid 14222511)
Glennon, R. A.; Naiman, N. A.; Pierson, M. E.; Titeler, M.; Lyon, R. A.; Weisberg, E. NAN-190: an arylpiperazine analog that antagonizes the stimulus effects of the 5-HT1A agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) Eur. J. Pharmacol. 1988, 154, 339-41
