Abstract

A new series of HDAC inhibitors were designed, synthesized, bearing acyl semicarbazide, hydrazide and hydrazide derivatives as ZBGs, alkyl thio oxadiazole as the linker group and coumarin as the cap group .These derivatives were evaluated for their HDACs inhibitory activities against MDA-MB-231 (a human breast cancer cell line) and HepG2 (a human hepatocellular carcinoma cell line), most of them had substantial HDAC inhibitory action and displayed better inhibitory activities against HepG2 cell line than against MDA-MB-231 cell line .Compound F5 was found to be the most powerful HDAC inhibitor, with an IC50 of 17.92,20.72 µg/ml which were better than that of SAHA's with IC50 = 39.84,36.52 µg/ml against MDA-MB-231 and HepG2 cell lines respectively . Compounds F1 with IC50 of 30.21,30.07 µg/ml, compounds F2 with IC50 of 31.59,26.27 µg/ml and compounds F5 with IC50 of 39.60 ,31.40 µg/ml higher than that of SAHA's with IC50 = 39.84,36.52 µg/ml against MDA-MB-231 and HepG2 cell lines respectively. The probable binding modes of compounds into HDAC enzymes (HDAC1 and 2) is deducted by the docking study which provided a rationale for the greatest inhibitory activity. These findings suggested that these compounds could be a good option for developing novel HDAC inhibitors with anticancer properties.