title: Quinolone-based HDAC inhibitors.
abstract: HDAC inhibitors emerged as promising drug candidates in combating wide variety of cancers. At present, two of the compounds SAHA and Romidepsin were approved by FDA for cutaneous T-cell lymphoma and many are in various clinical phases. A new quinolone cap structure was explored with hydroxamic acid as zinc-binding group (ZBG). The pan HDAC inhibitory and antiproliferative activities against three human cancer cell lines HCT-116 (colon), NCI-H460 (lung) and U251 (glioblastoma) of the compounds (4a-4w) were evaluated. Introduction of heterocyclic amines in CAP region increased the enzyme inhibitory and antiproliferative activities and few of the compounds tested are metabolically stable in both MLM and HLM.
authors.affiliation: Department of Medicinal Chemistry and.
authors.forename: Gopalan
authors.initials: G
authors.lastname: Balasubramanian
authors.forename: Narasimhan
authors.initials: N
authors.lastname: Kilambi
authors.forename: Suresh
authors.initials: S
authors.lastname: Rathinasamy
authors.forename: Praveen
authors.initials: P
authors.lastname: Rajendran
authors.forename: Shridhar
authors.initials: S
authors.lastname: Narayanan
authors.forename: Sridharan
authors.initials: S
authors.lastname: Rajagopal
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; D004354:Drug Screening Assays, Antitumor; D004789:Enzyme Activation / Q000187:drug effects; D045325:HCT116 Cells; D056572:Histone Deacetylase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006655:Histone Deacetylases / Q000378:metabolism*; D006801:Humans; D015394:Molecular Structure; D015363:Quinolones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D056572:Histone Deacetylase Inhibitors; D015363:Quinolones; D006655:Histone Deacetylases
keywords: Anticancer activity; HDAC inhibition; quinolone