title: Design, synthesis and preliminary evaluation of a series of histone deacetylase inhibitors carrying a benzodiazepine ring.
abstract: A series of new histone deacetylase inhibitors were designed and synthesized based on hybridization between SAHA or oxamflatin and 5-phenyl-1,4-benzodiazepines. The compounds were tested for their enzyme inhibitory activity on HeLa nuclear extracts, and on human recombinant HDAC1 and HDAC6. Antiproliferative activity was tested on different cancer cells types, while proapoptotic activity was primarily tested on NB4 cells. The compounds showed IC50 values similar to those of SAHA. Compound (S)-8 displayed interesting activity against hematological and solid malignancies.
authors.affiliation: NEUROFARBA, Department of Neuroscience, Psychology, Drug Research and Child Health, Section of Pharmaceutical and Nutraceutical Sciences, University of Florence, Via Ugo Schiff 6, 50019 Sesto Fiorentino, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Guandalini
authors.forename: M
authors.initials: M
authors.lastname: Balliu
authors.forename: C
authors.initials: C
authors.lastname: Cellai
authors.forename: M V
authors.initials: MV
authors.lastname: Martino
authors.forename: A
authors.initials: A
authors.lastname: Nebbioso
authors.forename: C
authors.initials: C
authors.lastname: Mercurio
authors.forename: V
authors.initials: V
authors.lastname: Carafa
authors.forename: G
authors.initials: G
authors.lastname: Bartolucci
authors.forename: S
authors.initials: S
authors.lastname: Dei
authors.forename: D
authors.initials: D
authors.lastname: Manetti
authors.forename: E
authors.initials: E
authors.lastname: Teodori
authors.forename: S
authors.initials: S
authors.lastname: Scapecchi
authors.forename: L
authors.initials: L
authors.lastname: Altucci
authors.forename: F
authors.initials: F
authors.lastname: Paoletti
authors.forename: M N
authors.initials: MN
authors.lastname: Romanelli
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D001569:Benzodiazepines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D060326:Chemistry Techniques, Synthetic; D015195:Drug Design; D056572:Histone Deacetylase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006655:Histone Deacetylases / Q000378:metabolism*; D006801:Humans; D012995:Solubility; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D056572:Histone Deacetylase Inhibitors; D001569:Benzodiazepines; D006655:Histone Deacetylases
keywords: 1,4-Benzodiazepine; 5-phenyl-1,4-benzodiazepine; AML; Antiproliferative activity; Apoptosis; BDZ; BOP-Cl; ER; Enantioselectivity; FXRQXSOJXFXFKW-UHFFFAOYSA-N; GQKBLEVLBFZGSR-UHFFFAOYSA-N; HDAC; HDAC inhibitors; HRABXMKDRVKZIZ-UXBLZVDNSA-N; NHGNWJXVKSKUTQ-UHFFFAOYSA-N; PGWVWMQPVNCSBB-UHFFFAOYSA-N; PKFJHSNYEZYYGI-UHFFFAOYSA-N; QNDUGSJDIKUKHC-UHFFFAOYSA-N; SAHA; SZERHQGPLCARMH-UHFFFAOYSA-N; XPOXSSWYTUEULK-UHFFFAOYSA-N; ZEZRNDUSXIQAAE-HNNXBMFYSA-N; acute myeloid leukemia; bis(2-oxo-3-oxazolidinyl)phosphonic chloride; eudismic ratio; histone deacetylase; suberoylanilide hydroxamic acid