Background: Histone deacetylases inhibitors (HDACIs) with different chemical structures
have been reported to play an important role in the treatment of cancer.
Objective: The study aims to modify the structure of Entinostat (MS-275) to discover new compounds
with improved anti-proliferative activities and perform SAR studies on this class of bioactive
Methods: Fourteen N-substituted benzamide derivatives were synthesized and their antiproliferative
activities were tested with four cancer cell lines (MCF-7, A549, K562 and MDA-MB-
231) by MTT assay.
Results: Compared with MS-275, six compounds exhibited comparable or even better antiproliferative
activities against specific/certain cancer cell lines.
Conclusion: The preliminary SARs showed that (ⅰ) the 2-substituent of the phenyl ring in the R
group and heteroatoms of amide which can chelate with zinc ion are critical to the antiproliferative
activity and (ⅱ) chlorine atom or nitro-group on the same benzene ring largely decreases
their anti-proliferative activity. Molecular docking study illustrated the interaction (binding
affinity) between the synthesized compounds and HDAC2 was observed to be similar to that of