tert‐Butylcarbamate‐Containing Histone Deacetylase Inhibitors: Apoptosis Induction, Cytodifferentiation, and Antiproliferative Activities in Cancer Cells

• DOI: 10.1002/cmdc.201300005
• Publication Date: 2013-03-25T10:40:08Z
• Authors: Sergio Valente; Daniela Trisciuoglio; Maria Tardugno; Rosaria Benedetti; Donatella Labella; Daniela Secci; Ciro Mercurio; Roberto Boggio; Stefano Tomassi; Salvatore Di Maro; Ettore Novellino; Lucia Altucci; Donatella Del Bufalo; Antonello Mai; Sandro Cosconati
• Keywords: K562 cells; Histone deacetylase inhibitor; Histone acetyltransferase; HDAC6

Abstract Herein we report novel pyrrole‐ and benzene‐based hydroxamates ( 8 , 10 ) 2′‐aminoanilides 9 11 bearing the tert ‐butylcarbamate group at CAP moiety as histone deacetylase (HDAC) inhibitors. Compounds b c selectively inhibited HDAC6 nanomolar level, whereas other effected an increase in acetyl‐α‐tubulin levels human acute myeloid leukemia U937 cells. In same cell line, compounds elicited 18.4 21.4 % apoptosis, respectively (SAHA: 16.9 %), pyrrole anilide displayed highest cytodifferentiating effect (90.9 %). tests against a wide range of various cancer lines to determine its antiproliferative effects, compound exhibited growth inhibition from sub‐micromolar (neuroblastoma LAN‐5 SH‐SY5Y cells, chronic K562 cells) low‐micromolar (lung H1299 A549, colon HCT116 HT29 concentrations. increased H3 acetylation, decreased colony‐forming potential cells by up 60 %.