title: Design of granulatimide and isogranulatimide analogues as potential Chk1 inhibitors: Study of amino-platforms for their synthesis.
abstract: The two marine alkaloids granulatimide and isogranulatimide have been shown to inhibit the checkpoint kinase 1 (Chk1), a promising target for cancer treatment. A molecular docking study allowing the design of new potential Chk1 inhibitors based on the natural products skeleton and the synthetic work to an amino-target platform to prepare them are described.
authors.affiliation: Laboratoire de Synthèse et Physicochimie de Molécules d'Intérêt Biologique, UMR CNRS 5068, Université Paul Sabatier, 118 route de Narbonne, 31062 Toulouse Cédex 9, France.
authors.forename: Hubert
authors.initials: H
authors.lastname: Lavrard
authors.affiliation: Laboratoire de Synthèse et Physicochimie de Molécules d'Intérêt Biologique, UMR CNRS 5068, Université Paul Sabatier, 118 route de Narbonne, 31062 Toulouse Cédex 9, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Rodriguez
authors.affiliation: Laboratoire de Synthèse et Physicochimie de Molécules d'Intérêt Biologique, UMR CNRS 5068, Université Paul Sabatier, 118 route de Narbonne, 31062 Toulouse Cédex 9, France. Electronic address: delfourn@chimie.ups-tlse.fr.
authors.forename: Evelyne
authors.initials: E
authors.lastname: Delfourne
mesh_terms: D000470:Alkaloids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000071877:Checkpoint Kinase 1; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D007093:Imidazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008958:Models, Molecular; D015394:Molecular Structure; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D011494:Protein Kinases / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D000470:Alkaloids; D007093:Imidazoles; D007211:Indoles; D047428:Protein Kinase Inhibitors; C433587:granulatimide; C116644:isogranulatimide; D011494:Protein Kinases; D000071877:Checkpoint Kinase 1
keywords: Chk1 inhibitors; Granulatimide; Isogranulatimide; Marine alkaloid