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Antiproliferative and differentiating activities of a novel series of histone deacetylase inhibitors.

ABSTRACT: Histone deacetylases are promising molecular targets for the development of antitumor agents. A novel series of histone deacetylase inhibitors of the hydroxamic acid type were synthesized for structure-activity studies. Thirteen tricyclic dibenzo-diazepine, -oxazepine, and -thiazepine analogues were studied and shown to induce variable degrees of histone H3/H4 and tubulin acetylation in a cellular model of myeloid leukemia sensitive to all-trans retinoic acid (ATRA). Multiparametric correlations between acetylation of the three substrates, tumor cell growth inhibition, and ATRA-dependent cytodifferentiation were performed, providing information on the chemical functionalities governing these activities. For two analogues, antitumor activity in the animal was demonstrated.

SUBMITTER: Binaschi M

PROVIDER: S-EPMC4007903 | biostudies-other | 2010 Nov

REPOSITORIES: biostudies-other

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Antiproliferative and differentiating activities of a novel series of histone deacetylase inhibitors.

Binaschi Monica M Boldetti Andrea A Gianni Maurizio M Maggi Carlo Alberto CA Gensini Martina M Bigioni Mario M Parlani Massimo M Giolitti Alessandro A Fratelli Maddalena M Valli Claudia C Terao Mineko M Garattini Enrico E

ACS medicinal chemistry letters 20100720 8

Histone deacetylases are promising molecular targets for the development of antitumor agents. A novel series of histone deacetylase inhibitors of the hydroxamic acid type were synthesized for structure-activity studies. Thirteen tricyclic dibenzo-diazepine, -oxazepine, and -thiazepine analogues were studied and shown to induce variable degrees of histone H3/H4 and tubulin acetylation in a cellular model of myeloid leukemia sensitive to all-trans retinoic acid (ATRA). Multiparametric correlations ...[more]

PMID: 24900225

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Thailandepsins: bacterial products with potent histone deacetylase inhibitory activities and broad-spectrum antiproliferative activities.

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