title: Design, synthesis, modeling, biological evaluation and photoaffinity labeling studies of novel series of photoreactive benzamide probes for histone deacetylase 2.
abstract: The design, modeling, synthesis, biological evaluation of a novel series of photoreactive benzamide probes for class I HDAC isoforms is reported. The probes are potent and selective for HDAC1 and 2 and are efficient in crosslinking to HDAC2 as demonstrated by photolabeling experiments. The probes exhibit a time-dependent inhibition of class I HDACs. The inhibitory activities of the probes were influenced by the positioning of the aryl and alkyl azido groups necessary for photocrosslinking and attachment of the biotin tag. The probes inhibited the deacetylation of H4 in MDA-MB-231 cell line, indicating that they are cell permeable and target the nuclear HDACs.
authors: Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago, Chicago, IL 60612, USA.
authors: Aditya Sudheer
authors: AS
authors: Vaidya
authors: Bhargava
authors: B
authors: Karumudi
authors: Emma
authors: E
authors: Mendonca
authors: Antonett
authors: A
authors: Madriaga
authors: Hazem
authors: H
authors: Abdelkarim
authors: Richard B
authors: RB
authors: van Breemen
authors: Pavel A
authors: PA
authors: Petukhov
mesh_terms: D000345:Affinity Labels / Q000737:chemistry*; D001549:Benzamides / Q000737:chemistry*; D001710:Biotin / Q000737:chemistry; D020134:Catalytic Domain; D045744:Cell Line, Tumor; D015195:Drug Design; D056284:Histone Deacetylase 1 / Q000737:chemistry / Q000378:metabolism; D056464:Histone Deacetylase 2 / Q000737:chemistry* / Q000378:metabolism; D056572:Histone Deacetylase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D011485:Protein Binding; D020033:Protein Isoforms / Q000737:chemistry / Q000378:metabolism
chemical_list: D000345:Affinity Labels; D001549:Benzamides; D056572:Histone Deacetylase Inhibitors; D020033:Protein Isoforms; D001710:Biotin; C037689:benzamide; D056284:Histone Deacetylase 1; D056464:Histone Deacetylase 2