title: Preparation, characterization and biological activity of C8-substituted cytokinins.
abstract: Naturally occurring cytokinins are adenine-based plant hormones. Although, the effect of various substituents at positions N1, C2, N3, N6, N7, or N9 on the biological activity of cytokinins has been studied, the C8-substituted compounds have received little attention. Here, we report the synthesis and in vitro biological testing of thirty-one cytokinin derivatives substituted at the C8 position of the adenine skeleton and twenty-seven compounds which served as their N9-tetrahydropyranyl protected precursors. The cytokinin activity of all the compounds was determined in classical cytokinin biotests (wheat leaf senescence, Amaranthus and tobacco callus assays). With some exceptions, the compounds with a N9-tetrahydropyranyl group were generally less active than their de-protected analogs. The latter were further tested for their ability to activate the Arabidopsis cytokinin receptors AHK3 and CRE1/AHK4 in bacterial receptor activation assays. Using this approach, we identified derivatives bearing short aliphatic chains and retaining high cytokinin activity. Such compounds are suitable candidates for fluorescence labeling or as protein-affinity ligands. We further found that some C8-substituted cytokinins exhibited no or lower cytotoxicity toward tobacco cells when compared to their parent compound. Therefore, we also present and discuss the cytotoxicity of all the compounds against three normal human cell lines.
authors.affiliation: Isotope Laboratory, Institute of Experimental Botany, AS CR, Vídeňská 1083, 14220 Prague 4, Czechia.
authors.forename: Lenka
authors.initials: L
authors.lastname: Zahajská
authors.affiliation: Isotope Laboratory, Institute of Experimental Botany, AS CR, Vídeňská 1083, 14220 Prague 4, Czechia; Laboratory of Growth Regulators, Centre of the Region Haná for Biotechnological and Agricultural Research, Institute of Experimental Botany, AS CR & Palacký University, Šlechtitelů 27, Olomouc 783 71, Czechia. Electronic address: jaroslav.nisler@gmail.com.
authors.forename: Jaroslav
authors.initials: J
authors.lastname: Nisler
authors.affiliation: Laboratory of Growth Regulators, Centre of the Region Haná for Biotechnological and Agricultural Research, Institute of Experimental Botany, AS CR & Palacký University, Šlechtitelů 27, Olomouc 783 71, Czechia.
authors.forename: Jiří
authors.initials: J
authors.lastname: Voller
authors.affiliation: Laboratory of Growth Regulators, Centre of the Region Haná for Biotechnological and Agricultural Research, Institute of Experimental Botany, AS CR & Palacký University, Šlechtitelů 27, Olomouc 783 71, Czechia.
authors.forename: Tomáš
authors.initials: T
authors.lastname: Gucký
authors.affiliation: Laboratory of Growth Regulators, Centre of the Region Haná for Biotechnological and Agricultural Research, Institute of Experimental Botany, AS CR & Palacký University, Šlechtitelů 27, Olomouc 783 71, Czechia.
authors.forename: Tomáš
authors.initials: T
authors.lastname: Pospíšil
authors.affiliation: Laboratory of Growth Regulators, Centre of the Region Haná for Biotechnological and Agricultural Research, Institute of Experimental Botany, AS CR & Palacký University, Šlechtitelů 27, Olomouc 783 71, Czechia.
authors.forename: Lukáš
authors.initials: L
authors.lastname: Spíchal
authors.affiliation: Laboratory of Growth Regulators, Centre of the Region Haná for Biotechnological and Agricultural Research, Institute of Experimental Botany, AS CR & Palacký University, Šlechtitelů 27, Olomouc 783 71, Czechia.
authors.forename: Miroslav
authors.initials: M
authors.lastname: Strnad
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives / Q000737:chemistry; D017360:Arabidopsis / Q000737:chemistry*; D003583:Cytokinins / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D010937:Plant Growth Regulators / Q000378:metabolism; D011494:Protein Kinases / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D003583:Cytokinins; D010937:Plant Growth Regulators; D011494:Protein Kinases; D000225:Adenine
keywords: AHK3 and CRE1/AHK4 bacterial receptor assay; C8-substituted cytokinin; Cytokinin bioassay; Organic synthesis