690-699One of the recent targets is histone deacetylase (HDAC) which provide a very promising new approach for anticancer drugs, which may combine clinical efficacy with relatively mild toxicological side effects. Modification of histone acetylation level, promoted by histone acetylase (HAT) and HDAC enzyme, has been recognize to play an important role in epigenetic modulation of gene expression, so HDAC inhibitors are considered a new class of anticancer agents. A new series of hydroxamic and carboxylic acid analogues based on the 1,3,4-thiadiazole scaffold has been designed and synthesized with the aim of exploring its potential as new antitumor agents. Biological results have revealed that the structural modifications proposed significantly affected inhibitory potency as well as selectivity for HDAC inhibitors. Most target compounds are significantly more active, specifically 5a, 5b, 5e with IC50 values in the low micromolar or, the most active compounds in the series. Selected compounds have been tested on the viability of MDA-MB-231 (breast cancer cell) and K562 (chronic myelogenous leukemia cell), A549 (human lung cancer), PC3 (Prostate cancer cell lines) using MTT assay. Docking simulations suggested that the most active compounds can recognize the binding site (PDB Code 1w22 reference compound) using a similar interactions network. These results have allowed us to rationalize the observed structure–activity relationships
