Syntheses and Biological Evaluation of Novel Hydroxamic Acid Derivatives Containing Purine Moiety as Histone Deacetylase Inhibitors.

Abstract:

:The novel hydroxamates containing purine scaffold were designed, synthesized and screened for their biological activities as histone deacetylase (HDAC) inhibitors. Some of them exhibited excellent acti-HDACs activities and antiproliferative activities, the most promising compound was 7m'. Western blot analysis indicated the compounds 7f', 7l', 7m', 7o' could increase histone H3 acetylation levels in HCT116 and K562 cell lines, and 7m' increased the level of acetyl histone H3 in a dose-dependent manner, which is similar to the behavior of suberoylanilide hydroxamic acid (SAHA). Molecular docking study revealed that the conformation of 7m' in the active site of HDAC2 was similar to positive drug SAHA, which were oriented with the hydroxamic acid towards the catalytic center and formed metal binding with zinc ion.

authors

Xu Z,Yang Y,Mai X,Liu B,Xiong Y,Feng L,Liao Y,Zhang Y,Wang H,Ouyang L,Liu S

doi

10.1248/cpb.c17-00997

subject

Has Abstract

pub_date

2018-01-01 00:00:00

pages

439-451

issue

4

eissn

0009-2363

issn

1347-5223

journal_volume

66

pub_type

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