title: Structure-activity relationships of β-hydroxyphosphonate nucleoside analogues as cytosolic 5'-nucleotidase II potential inhibitors: synthesis, in vitro evaluation and molecular modeling studies.
abstract: The cytosolic 5'-nucleotidase II (cN-II) has been proposed as an attractive molecular target for the development of novel drugs circumventing resistance to cytotoxic nucleoside analogues currently used for treating leukemia and other malignant hemopathies. In the present work, synthesis of β-hydroxyphosphonate nucleoside analogues incorporating modifications either on the sugar residue or the nucleobase, and their in vitro evaluation towards the purified enzyme were carried out in order to determine their potency towards the inhibition of cN-II. In addition to the biochemical investigations, molecular modeling studies revealed important structural features for binding affinities towards the target enzyme.
authors.affiliation: Institut des biomolécules Max Mousseron (IBMM), UMR 5247 CNRS - UM1 - UM2, Université Montpellier 2, cc1705, Place Eugène Bataillon, 34095 Montpellier cedex 5, France.
authors.forename: Maïa
authors.initials: M
authors.lastname: Meurillon
authors.affiliation: Centre d'études d'agents pathogènes et biotechnologies pour la santé (CPBS), UMR 5236 CNRS - UM1 - UM2, 1919 route de Mende, 34293 Montpellier cedex 5, France.
authors.forename: Zsuzsanna
authors.initials: Z
authors.lastname: Marton
authors.affiliation: Institut des biomolécules Max Mousseron (IBMM), UMR 5247 CNRS - UM1 - UM2, Université Montpellier 2, cc1705, Place Eugène Bataillon, 34095 Montpellier cedex 5, France.
authors.forename: Audrey
authors.initials: A
authors.lastname: Hospital
authors.affiliation: Université de Lyon 1, INSERM U1052 CNRS UMR 5286, Centre de Recherche en Cancérologie de Lyon (CRCL), Centre Léon Bérard, 69000 Lyon, France.
authors.forename: Lars Petter
authors.initials: LP
authors.lastname: Jordheim
authors.affiliation: Institut des biomolécules Max Mousseron (IBMM), UMR 5247 CNRS - UM1 - UM2, Université Montpellier 2, cc1705, Place Eugène Bataillon, 34095 Montpellier cedex 5, France.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Béjaud
authors.affiliation: Centre d'études d'agents pathogènes et biotechnologies pour la santé (CPBS), UMR 5236 CNRS - UM1 - UM2, 1919 route de Mende, 34293 Montpellier cedex 5, France.
authors.forename: Corinne
authors.initials: C
authors.lastname: Lionne
authors.affiliation: Université de Lyon 1, INSERM U1052 CNRS UMR 5286, Centre de Recherche en Cancérologie de Lyon (CRCL), Centre Léon Bérard, 69000 Lyon, France.
authors.forename: Charles
authors.initials: C
authors.lastname: Dumontet
authors.affiliation: Institut des biomolécules Max Mousseron (IBMM), UMR 5247 CNRS - UM1 - UM2, Université Montpellier 2, cc1705, Place Eugène Bataillon, 34095 Montpellier cedex 5, France.
authors.forename: Christian
authors.initials: C
authors.lastname: Périgaud
authors.affiliation: Centre d'études d'agents pathogènes et biotechnologies pour la santé (CPBS), UMR 5236 CNRS - UM1 - UM2, 1919 route de Mende, 34293 Montpellier cedex 5, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Chaloin
authors.affiliation: Institut des biomolécules Max Mousseron (IBMM), UMR 5247 CNRS - UM1 - UM2, Université Montpellier 2, cc1705, Place Eugène Bataillon, 34095 Montpellier cedex 5, France. Electronic address: suzanne.peyrottes@univ-montp2.fr.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Peyrottes
mesh_terms: D015720:5'-Nucleotidase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D008958:Models, Molecular; D008968:Molecular Conformation; D009705:Nucleosides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D063065:Organophosphonates / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D004791:Enzyme Inhibitors; D009705:Nucleosides; D063065:Organophosphonates; D015720:5'-Nucleotidase; C508048:NT5C2 protein, human
keywords: Enzyme inhibitors; Leukemia; Nucleotides; Phosphonate