title: Generation and Assessment of Fusions Between HDACi and TKi.
abstract: Chimeric compounds combine the structural features of inhibitors of histone deacetylases (HDACi) and tyrosine kinase inhibitors (TKi), and therefore unite the effects of a dual-targeting strategy in one compound. Here, we describe the generation of such hybrid molecules. Small molecules, known as TKi, are combined with a Zn2+chelating motive, preferentially a hydroxamic acid, in addition. The resulting small molecules also can inhibit histone deacetylases, which are dependent on the catalytically active Zn2+. Moreover, we summarize how the growth-inhibitory effects of these combined compounds can be determined with a simple proliferation assay with a leukemic cell line.
authors.affiliation: Faculty of Chemistry and Pharmacy, Institute of Pharmacy, University of Regensburg, Universitätsstraße 31, Regensburg, D-93040, Germany. siavosh.mahboobi@chemie.uni-regensburg.de.
authors.forename: Siavosh
authors.initials: S
authors.lastname: Mahboobi
authors.affiliation: Faculty of Chemistry and Pharmacy, Institute of Pharmacy, University of Regensburg, Universitätsstraße 31, Regensburg, D-93040, Germany.
authors.forename: Bernadette
authors.initials: B
authors.lastname: Pilsl
authors.affiliation: Faculty of Chemistry and Pharmacy, Institute of Pharmacy, University of Regensburg, Universitätsstraße 31, Regensburg, D-93040, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Sellmer
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002413:Cations, Divalent; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002614:Chelating Agents / Q000737:chemistry* / Q000494:pharmacology; D060326:Chemistry Techniques, Synthetic; D015870:Gene Expression; D056572:Histone Deacetylase Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism; D006801:Humans; D006877:Hydroxamic Acids / Q000737:chemistry* / Q000494:pharmacology; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D047428:Protein Kinase Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D015032:Zinc / Q000737:chemistry; D051941:fms-Like Tyrosine Kinase 3 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D002413:Cations, Divalent; D002614:Chelating Agents; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D047428:Protein Kinase Inhibitors; C497970:FLT3 protein, human; D051941:fms-Like Tyrosine Kinase 3; D006655:Histone Deacetylases; D015032:Zinc
keywords: Chimeric molecules; Dual targeting strategy; Histone deacetylase inhibitor; Hybrid structures; Proliferation assay; Tyrosine kinase inhibitor