title: Design, synthesis and anticancer activity of piperazine hydroxamates and their histone deacetylase (HDAC) inhibitory activity.
abstract: Six compounds were synthesized with piperazine in linker region and hydroxamate as Zinc Binding Group (ZBG). They were screened against three cancer cell-lines (NCIH460; HCT116; U251). Compounds 5c and 5f with GI(50) value of 9.33+/-1.3 microM and 12.03+/-4 microM, respectively, were tested for their inhibitory potential on hHDAC8. Compound 5c had IC(50) of 33.67 microM. Compounds were also screened for their anticancer activity against HL60 human promyelocytic leukemia cell line due to the presence of pharmacophoric features of RR inhibitors in them. Compound 5c had IC(50) of 0.6 microM at 48h.
authors.affiliation: Department of Pharmaceutical Sciences, Birla Institute of Technology, Mesra, Ranchi, Jharkhand, India.
authors.forename: Bhadaliya
authors.initials: B
authors.lastname: Chetan
authors.forename: Mahesh
authors.initials: M
authors.lastname: Bunha
authors.forename: Monika
authors.initials: M
authors.lastname: Jagrat
authors.forename: Barij Nayan
authors.initials: BN
authors.lastname: Sinha
authors.forename: Philipp
authors.initials: P
authors.lastname: Saiko
authors.forename: Geraldine
authors.initials: G
authors.lastname: Graser
authors.forename: Thomas
authors.initials: T
authors.lastname: Szekeres
authors.forename: Ganapathy
authors.initials: G
authors.lastname: Raman
authors.forename: Praveen
authors.initials: P
authors.lastname: Rajendran
authors.forename: Dhatchana
authors.initials: D
authors.lastname: Moorthy
authors.forename: Arijit
authors.initials: A
authors.lastname: Basu
authors.forename: Venkatesan
authors.initials: V
authors.lastname: Jayaprakash
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D056572:Histone Deacetylase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006655:Histone Deacetylases / Q000378:metabolism*; D006801:Humans; D006877:Hydroxamic Acids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008958:Models, Molecular; D015394:Molecular Structure; D000077489:Piperazine; D010879:Piperazines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D010879:Piperazines; D000077489:Piperazine; D006655:Histone Deacetylases