biostudies-otherUnknown1(8)Binaschi MACS medicinal chemistry letters411-5https://www.ebi.ac.uk/biostudies/studies/S-EPMC4007903Histone 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.biostudies-otherPMC4007903Europe PMCBigioni MBoldetti AFratelli MValli CTerao MBinaschi MGensini MGiolitti AMaggi CAGarattini EGianni MParlani MfalseAntiproliferative and differentiating activities of a novel series of histone deacetylase inhibitors.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.2010-01-01T00:00:00Z2010 Nov2019-03-27T01:27:30Z2019-03-27T01:27:30ZS-EPMC40079032490022510.1021/ml1001163