title: Potent and selective HDAC6 inhibitory activity of N-(4-hydroxycarbamoylbenzyl)-1,2,4,9-tetrahydro-3-thia-9-azafluorenes as novel sulfur analogues of Tubastatin A.
abstract: Eight N-(4-hydroxycarbamoylbenzyl)-1,2,4,9-tetrahydro-3-thia-9-azafluorenes were efficiently prepared as sulfur analogues of Tubastatin A and thus evaluated as new HDAC6 inhibitors. All compounds exhibited potency against HDAC6, and four of them were active in the nanomolar range (IC(50) = 1.9-22 nM). Further analysis revealed that the sulfone derivatives (designated as Tubathians) are superior to their non-oxidized sulfide analogues, and the two most active sulfones showed good to excellent HDAC6 selectivity compared to all other HDAC isoform classes.
authors.affiliation: SynBioC Research Group, Department of Sustainable Organic Chemistry and Technology, Faculty of Bioscience Engineering, Ghent University, Coupure Links 653, B-9000 Ghent, Belgium.
authors.forename: Rob
authors.initials: R
authors.lastname: De Vreese
authors.forename: Tom
authors.initials: T
authors.lastname: Verhaeghe
authors.forename: Tom
authors.initials: T
authors.lastname: Desmet
authors.forename: Matthias
authors.initials: M
authors.lastname: D'hooghe
mesh_terms: D001372:Aza Compounds / Q000737:chemistry; D001665:Binding Sites; D020134:Catalytic Domain; D005449:Fluorenes / Q000737:chemistry*; D056572:Histone Deacetylase Inhibitors / Q000737:chemistry* / Q000378:metabolism; D006655:Histone Deacetylases / Q000737:chemistry* / Q000378:metabolism; D006877:Hydroxamic Acids / Q000737:chemistry* / Q000378:metabolism; D007211:Indoles / Q000737:chemistry* / Q000378:metabolism; D062105:Molecular Docking Simulation; D011485:Protein Binding; D013450:Sulfones / Q000737:chemistry
chemical_list: D001372:Aza Compounds; D005449:Fluorenes; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D007211:Indoles; D013450:Sulfones; C553587:tubastatin A; D006655:Histone Deacetylases