title: Discovery of adamantane based highly potent HDAC inhibitors.
abstract: Herein, we report the development of highly potent HDAC inhibitors for the treatment of cancer. A series of adamantane and nor-adamantane based HDAC inhibitors were designed, synthesized and screened for the inhibitory activity of HDAC. A number of compounds exhibited GI50 of 10-100 nM in human HCT116, NCI-H460 and U251 cancer cells, in vitro. Compound 32 displays efficacy in human tumour animal xenograft model.
authors.affiliation: Drug Discovery Research Centre, Orchid Chemicals & Pharmaceuticals Ltd, Chennai 600119, India.
authors.forename: Balasubramanian
authors.initials: B
authors.lastname: Gopalan
authors.forename: Thanasekaran
authors.initials: T
authors.lastname: Ponpandian
authors.forename: Virendra
authors.initials: V
authors.lastname: Kachhadia
authors.forename: Kuppusamy
authors.initials: K
authors.lastname: Bharathimohan
authors.forename: Radhakrishnan
authors.initials: R
authors.lastname: Vignesh
authors.forename: Velaiah
authors.initials: V
authors.lastname: Sivasudar
authors.forename: Shridhar
authors.initials: S
authors.lastname: Narayanan
authors.forename: Bhonde
authors.initials: B
authors.lastname: Mandar
authors.forename: Rajendran
authors.initials: R
authors.lastname: Praveen
authors.forename: Nithyanandan
authors.initials: N
authors.lastname: Saranya
authors.forename: Sriram
authors.initials: S
authors.lastname: Rajagopal
authors.forename: Sridharan
authors.initials: S
authors.lastname: Rajagopal
mesh_terms: D000218:Adamantane / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry* / Q000627:therapeutic use; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D004354:Drug Screening Assays, Antitumor; D045325:HCT116 Cells; D056572:Histone Deacetylase Inhibitors / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use; D006655:Histone Deacetylases / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy; D051379:Mice; D016513:Mice, SCID; D013329:Structure-Activity Relationship; D014183:Transplantation, Heterologous
chemical_list: D000970:Antineoplastic Agents; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases; D000218:Adamantane