792935-96-7Relevant academic research and scientific papers
Novel inhibitors of human histone deacetylases: Design, synthesis, enzyme inhibition, and cancer cell growth inhibition of SAHA-based non-hydroxamates
Suzuki, Takayoshi,Nagano, Yuki,Kouketsu, Akiyasu,Matsuura, Azusa,Maruyama, Sakiko,Kurotaki, Mineko,Nakagawa, Hidehiko,Miyata, Naoki
, p. 1019 - 1032 (2007/10/03)
To find novel non-hydroxamate histone deacetylase (HDAC) inhibitors, a series of compounds modeled after suberoylanilide hydroxamic acid (SAHA) was designed and synthesized. In this series, compound 7, in which the hydroxamic acid of SAHA is replaced by a thiol, was found to be as potent as SAHA, and optimization of this series led to the identification of HDAC inhibitors more potent than SAHA. In cancer cell growth inhibition assay, S-isobutyryl derivative 51 showed strong activity, and its potency was comparable to that of SAHA. The cancer cell growth inhibitory activity was verified to be the result of histone hyperacetylation and subsequent induction of p21WAF1/CIP1 by Western blot analysis. Kinetical enzyme assay and molecular modeling suggest the thiol formed by enzymatic hydrolysis within the cell interacts with the zinc ion in the active site of HDACs.
β-Cyclodextrin Host-Guest Complexes Probed under Thermodynamic Equilibrium: Thermodynamics and AFM Force Spectroscopy
Auletta, Tommaso,De Jong, Menno R.,Mulder, Alart,Van Veggel, Frank C. J. M.,Huskens, Jurriaan,Reinhoudt, David N.,Zou, Shan,Zapotoczny, Szczepan,Schoenherr, Holger,Vancso, G. Julius,Kuipers, Laurens
, p. 1577 - 1584 (2007/10/03)
The rupture forces of individual host-guest complexes between β-cyclodextrin (β-CD) heptathioether monolayers on Au(111) and several surface-confined guests were measured in aqueous medium by single molecule force spectroscopy using an atomic force microscope, Anilyl, toluidyl, tert-butylphenyl, and adamantylthiolss (0.2-1%) were immobilized in mixed monolayers with 2-mercaptoethanol on gold-coated AFM tips, For all guests and for all surface coverages, the force-displacement curves measured between the functionalized tips and monolayers of β-CD exhibited single, as well as multiple, pull-off events, The histograms of the pull-off forces showed several maxima at equidistant forces, with force quanta characteristic for each guest of 39 ± 15, 45 ± 15, 89 ± 15, and 102 ± 15 pN, respectively. These force quanta were independent of the loading rate, indicating that, because of the fast complexation/decomplexation kinetics, the rupture forces were probed under thermodynamic equilibrium. The force values followed the same trend as the free binding energy ΔG° measured for model guest compounds in solution or on β-CD monolayers, as determined by microcalorimetry and surface plasmon resonance measurements, respectively, A descriptive model was developed to correlate quantitatively the pull-off force values with the ΔG° of the complexes, based on the evaluation of the energy potential landscape of tip-surface interaction.
Thiol-based SAHA analogues as potent histone deacetylase inhibitors
Suzuki, Takayoshi,Kouketsu, Akiyasu,Matsuura, Azusa,Kohara, Arihiro,Ninomiya, Shin-Ichi,Kohda, Kohfuku,Miyata, Naoki
, p. 3313 - 3317 (2007/10/03)
In order to find novel nonhydroxamate histone deacetylase (HDAC) inhibitors, a series of thiol-based compounds modeled after suberoylanilide hydroxamic acid (SAHA) was synthesized, and their inhibitory effect on HDACs was evaluated. Compound 6, in which t
