title: Synthesis and biological effects of new hybrid compounds composed of benzylguanidines and the alkylating group of busulfan on neuroblastoma cells.
abstract: (131)Iodine-labelled (meta-iodobenzyl)guanidine ([(131)I]-mIBG) and busulfan [butane-1,4-diylbis(methanesulfonate)] are well-established pharmaceuticals in neuroblastoma therapy. We report the design, synthesis, and testing of hybrid molecules-mBBG and pBBG-which combine key structural features of (meta-iodobenzyl)guanidine and busulfan: they contain a benzylguanidine moiety for accumulating in neuroblastoma cells via the noradrenaline transporter and, in the meta- or para-position, respectively, one of the two identical alkylating motives of busulfan for killing cells. Uptake and toxicity of hybrids mBBG and pBBG in human neuroblastoma cells compared favorably to their ancestors [(131)I]-mIBG and busulfan.
authors.affiliation: Institut für Organische Chemie, Albert-Ludwigs-Universität Freiburg, Albertstraße 21, D-79104 Freiburg, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Hampel
authors.affiliation: Children's University Hospital, Hoppe-Seyler-Str.1, D-72076 Tübingen, Germany.
authors.forename: Marietta
authors.initials: M
authors.lastname: Bruns
authors.affiliation: Children's University Hospital, Hoppe-Seyler-Str.1, D-72076 Tübingen, Germany.
authors.forename: Melanie
authors.initials: M
authors.lastname: Bayer
authors.affiliation: Children's University Hospital, Hoppe-Seyler-Str.1, D-72076 Tübingen, Germany.
authors.forename: Rupert
authors.initials: R
authors.lastname: Handgretinger
authors.affiliation: Children's University Hospital, Hoppe-Seyler-Str.1, D-72076 Tübingen, Germany. Electronic address: gernot.bruchelt@med.uni-tuebingen.de.
authors.forename: Gernot
authors.initials: G
authors.lastname: Bruchelt
authors.affiliation: Institut für Organische Chemie, Albert-Ludwigs-Universität Freiburg, Albertstraße 21, D-79104 Freiburg, Germany. Electronic address: reinhard.brueckner@organik.chemie.uni-freiburg.de.
authors.forename: Reinhard
authors.initials: R
authors.lastname: Brückner
mesh_terms: D000478:Alkylation; D002066:Busulfan / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D006146:Guanidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D015394:Molecular Structure; D009447:Neuroblastoma / Q000188:drug therapy; D014407:Tumor Cells, Cultured
chemical_list: D006146:Guanidines; C117872:benzylguanidine; D002066:Busulfan
keywords: Alkylating agent; Busulfan; Neuroblastoma; meta-Iodobenzylguanidine (mIBG)