Aim:
Background: The causes of Carcinogen could be genetic and epigenetic. Histone modification play a major role in gene expression regulation. The inhibition of HDAC enzyme will lead to arrest cell cycle, differentiation, angiogenesis decreasing, immune response modulation and ultimately cell death. According to the crystal structures of [HDAC6] catalytic domains the requirement of [HDAC6] inhibitors designed. Aims: Synthesis Four new Coumarin-Sulfonamide derivatives as histone deacetylase inhibitors.

Material and methods:
Materials and methods: The utilization of sulfonamide as zinc binding group and Coumarin as cap groups known to possess antitumor activity in the designed of new histone deacetylase inhibitors.

Results:
Results: Four compounds have been synthesized and characterized successfully by ART-FTIR, NMR and ESI-Ms. The synthesized compound showed growth inhibition of hepatoblastoma HepG2 (IC50, I=47.52, II=18.53, III=15.44, IV=19.81, vorinostat=37.50) and human colon adenocarcinoma MCF-7 (IC50, I=67.59, II=23.33, III= 30.88, IV=25.63, vorinostat=28.41). The binding mode to the active site of [HDAC6] were determined by docking study which give results that they might be good inhibitors for [HDAC6].

Conclusions:
Conclusions: The synthesized compounds (I, II, III and IV) showed cytotoxicity toward MCF-7 and HepG2 cancer cell lines and their docking analysis provided a preliminary indication that they are viable [HDAC6] candidates.