title: Synthesis of Dynole 34-2, Dynole 2-24 and Dyngo 4a for investigating dynamin GTPase.
abstract: Dynamin is a large GTPase with roles in membrane fission during clathrin-mediated endocytosis, in actin dynamics and in cytokinesis. Defects in dynamin have been linked to human diseases. The synthesis of a dynamin modulator toolkit comprising two different inhibitor classes is described. The first series comprises Dynole 34-2, Dynole 2-24 and the inactive control Dynole 31-2. The Dynole compounds act on the dynamin G domain, are not GTP competitive and can be synthesized in 2-3 d. Knoevenagel condensation of 1-(3-(dimethylamino)propyl)-1H-indole-3-carbaldehyde (1) with cyanoamides (2 and 3) affords Dynole 31-2 and Dynole 34-2, respectively. Reductive amination of 1 with decylamine gives Dynole 2-24. The second series acts at an allosteric site in the G domain of dynamin and comprises Dyngo 4a and Dyngo Ø (inactive control). Both are synthesized in an overnight reaction via condensation of 3-hydroxy-2-naphthoic hydrazide with 2,4,5-trihydroxybenzaldehyde to afford Dyngo 4a, or with benzaldehyde to afford Dyngo Ø.
authors.affiliation: 1] Chemistry, Centre for Chemical Biology, School of Environmental and Life Sciences, University of Newcastle, University Drive, Callaghan, New South Wales, Australia. [2].
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Robertson
authors.affiliation: 1] Chemistry, Centre for Chemical Biology, School of Environmental and Life Sciences, University of Newcastle, University Drive, Callaghan, New South Wales, Australia. [2].
authors.forename: Fiona M
authors.initials: FM
authors.lastname: Deane
authors.affiliation: Cell Signalling Unit, Children's Medical Research Institute, The University of Sydney, Sydney, New South Wales, Australia.
authors.forename: Phillip J
authors.initials: PJ
authors.lastname: Robinson
authors.affiliation: Chemistry, Centre for Chemical Biology, School of Environmental and Life Sciences, University of Newcastle, University Drive, Callaghan, New South Wales, Australia.
authors.forename: Adam
authors.initials: A
authors.lastname: McCluskey
mesh_terms: D000495:Allosteric Site; D060326:Chemistry Techniques, Synthetic; D003487:Cyanoacrylates / Q000138:chemical synthesis*; D034281:Dynamins / Q000737:chemistry*; D006835:Hydrazones / Q000138:chemical synthesis*; D007211:Indoles / Q000138:chemical synthesis*; D009284:Naphthols / Q000138:chemical synthesis*
chemical_list: D003487:Cyanoacrylates; D006835:Hydrazones; D007211:Indoles; C579722:N-((1-(3-(dimethylamino)propyl)-1H-indol-3-yl)methyl)decan-1-amine; D009284:Naphthols; C568360:dyngo-4a; C000597838:dynole 34-2; D034281:Dynamins