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The new low-toxic histone deacetylase inhibitor S-(2) induces apoptosis in various acute myeloid leukaemia cells.

Cellai C, Balliu M, Laurenzana A, Guandalini L, Matucci R, Miniati D, Torre E, Nebbioso A, Carafa V, Altucci L, Romanelli MN, Paoletti F - J. Cell. Mol. Med. (2012)

Bottom Line: Moreover, novel HDACi prompted p53 and α-tubulin acetylation and, consistently, inhibited HDAC1 and 6 activity.Importantly, (S)-2 was safe in mice (up to 150 mg/kg/week) as determined by liver, spleen, kidney and bone marrow histopathology; and displayed negligible affinity for peripheral/central BDZ-receptors.Overall, the BDZ-hydroxamate (S)-2 showed to be a low-toxic HDACi with powerful anti-proliferative and pro-apototic activities towards different cultured and primary AML cells, and therefore of clinical interest to support conventional anti-leukaemic therapy.

View Article: PubMed Central - PubMed

Affiliation: Department of Experimental Pathology and Oncology, University of Florence, Sesto Fiorentino, Italy.

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Chemical structures of compounds used in this work. The numbers labelling the compounds are the same as in ref. [11].
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fig01: Chemical structures of compounds used in this work. The numbers labelling the compounds are the same as in ref. [11].

Mentions: The 1,4-benzodiazepine ring (5-phenyl-1,3-dihydro-2-oxo-benzo[e][1,4]-diazepine) was used as the cap of novel hydroxamic-based HDACi [11]. The chiral compounds (S)-2 and (R)-2, and their non-chiral analogue 4 (Fig. 1) were dissolved in dimethyl sulfoxide (DMSO; Sigma-Aldrich, St. Louis, MO, USA), stored as 0.1 M stock solutions in the dark at room temperature and added directly to the culture. The amount of DMSO used as the vehicle did not interfere with drug biological activities. All other chemicals were reagent grade.


The new low-toxic histone deacetylase inhibitor S-(2) induces apoptosis in various acute myeloid leukaemia cells.

Cellai C, Balliu M, Laurenzana A, Guandalini L, Matucci R, Miniati D, Torre E, Nebbioso A, Carafa V, Altucci L, Romanelli MN, Paoletti F - J. Cell. Mol. Med. (2012)

Chemical structures of compounds used in this work. The numbers labelling the compounds are the same as in ref. [11].
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3822689&req=5

fig01: Chemical structures of compounds used in this work. The numbers labelling the compounds are the same as in ref. [11].
Mentions: The 1,4-benzodiazepine ring (5-phenyl-1,3-dihydro-2-oxo-benzo[e][1,4]-diazepine) was used as the cap of novel hydroxamic-based HDACi [11]. The chiral compounds (S)-2 and (R)-2, and their non-chiral analogue 4 (Fig. 1) were dissolved in dimethyl sulfoxide (DMSO; Sigma-Aldrich, St. Louis, MO, USA), stored as 0.1 M stock solutions in the dark at room temperature and added directly to the culture. The amount of DMSO used as the vehicle did not interfere with drug biological activities. All other chemicals were reagent grade.

Bottom Line: Moreover, novel HDACi prompted p53 and α-tubulin acetylation and, consistently, inhibited HDAC1 and 6 activity.Importantly, (S)-2 was safe in mice (up to 150 mg/kg/week) as determined by liver, spleen, kidney and bone marrow histopathology; and displayed negligible affinity for peripheral/central BDZ-receptors.Overall, the BDZ-hydroxamate (S)-2 showed to be a low-toxic HDACi with powerful anti-proliferative and pro-apototic activities towards different cultured and primary AML cells, and therefore of clinical interest to support conventional anti-leukaemic therapy.

View Article: PubMed Central - PubMed

Affiliation: Department of Experimental Pathology and Oncology, University of Florence, Sesto Fiorentino, Italy.

Show MeSH
Related in: MedlinePlus